769 results on '"Kamen, Diane L."'
Search Results
2. Predictors of British Isles Lupus Assessment Group-based outcomes in patients with systemic lupus erythematosus: Analysis from the Systemic Lupus International Collaborating Clinics Inception Cohort
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David, Trixy, Su, Li, Cheng, Yafeng, Gordon, Caroline, Parker, Benjamin, Isenberg, David, Reynolds, John A, Bruce, Ian N, Hanly, John G, Bae, Sang-Cheol, Romero-Diaz, Juanita, Sanchez-Guerrero, Jorge, Bernatsky, Sasha, Clarke, Ann E, Wallace, Daniel J, Rahman, Anisur, Merrill, Joan T, Fortin, Paul R, Gladman, Dafna D, Urowitz, Murray B, Petri, Michelle, Ginzler, Ellen M, Dooley, MA, Ramsey-Goldman, Rosalind, Manzi, Susan, Jonsen, Andreas, Alarcón, Graciela S, van Vollenhoven, Ronald F, Aranow, Cynthia, Mackay, Meggan, Ruiz-Irastorza, Guillermo, Lim, S Sam, Inanc, Murat, Kalunian, Kenneth C, Jacobsen, Soren, Peschken, Christine A, Kamen, Diane L, Askanase, Anca, Payne, Katherine, Lunt, Mark, Peek, Niels, Geifman, Nophar, Gavan, Sean, Armitt, Gillian, Doherty, Patrick, Prattley, Jennifer, Azadbakht, Narges, Papazian, Angela, Le Sueur, Helen, Farrelly, Carmen, Richardson, Clare, Shabbir, Zunnaira, Hewitt, Lauren, McHugh, Neil, Reynolds, John, Young, Stephen, Jayne, David, Farewell, Vern, Pickering, Matthew, Lightstone, Elizabeth, Gilmore, Alyssa, Botto, Marina, Vyse, Timothy, Morris, David Lester, D’Cruz, D, Vital, Edward, Wittmann, Miriam, Emery, Paul, Beresford, Michael, Hedrich, Christian, Midgley, Angela, Gritzfeld, Jenna, Ehrenstein, Michael, Parvaz, Mariea, Dunnage, Jane, Batchelor, Jane, Holland, E, and Upsall, Pauline
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Biomedical and Clinical Sciences ,Clinical Sciences ,Autoimmune Disease ,Lupus ,Clinical Research ,Humans ,Lupus Erythematosus ,Systemic ,Immunosuppressive Agents ,Outcome Assessment ,Health Care ,Logistic Models ,United Kingdom ,Severity of Illness Index ,International Collaborating Clinics Consortium ,MASTERPLANS Consortium ,Systemic lupus erythematosus ,clinical outcomes ,disease activity ,predictors ,Arthritis & Rheumatology ,Clinical sciences - Abstract
BackgroundWe aimed to identify factors associated with a significant reduction in SLE disease activity over 12 months assessed by the BILAG Index.MethodsIn an international SLE cohort, we studied patients from their 'inception enrolment' visit. We also defined an 'active disease' cohort of patients who had active disease similar to that needed for enrolment into clinical trials. Outcomes at 12 months were; Major Clinical Response (MCR: reduction to classic BILAG C in all domains, steroid dose of ≤7.5 mg and SLEDAI ≤ 4) and 'Improvement' (reduction to ≤1B score in previously active organs; no new BILAG A/B; stable or reduced steroid dose; no increase in SLEDAI). Univariate and multivariate logistic regression with Least Absolute Shrinkage and Selection Operator (LASSO) and cross-validation in randomly split samples were used to build prediction models.Results'Inception enrolment' (n = 1492) and 'active disease' (n = 924) patients were studied. Models for MCR performed well (ROC AUC = .777 and .732 in the inception enrolment and active disease cohorts, respectively). Models for Improvement performed poorly (ROC AUC = .574 in the active disease cohort). MCR in both cohorts was associated with anti-malarial use and inversely associated with active disease at baseline (BILAG or SLEDAI) scores, BILAG haematological A/B scores, higher steroid dose and immunosuppressive use.ConclusionBaseline predictors of response in SLE can help identify patients in clinic who are less likely to respond to standard therapy. They are also important as stratification factors when designing clinical trials in order to better standardize overall usual care response rates.
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- 2023
3. Retinal toxicity in a multinational inception cohort of patients with systemic lupus on hydroxychloroquine
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Almeida-Brasil, Celline C, Hanly, John G, Urowitz, Murray, Clarke, Ann Elaine, Ruiz-Irastorza, Guillermo, Gordon, Caroline, Ramsey-Goldman, Rosalind, Petri, Michelle A, Ginzler, Ellen M, Wallace, Daniel J, Bae, Sang-Cheol, Romero-Diaz, Juanita, Dooley, Mary-Anne, Peschken, Christine, Isenberg, David, Rahman, Anisur, Manzi, Susan, Jacobsen, Søren, Lim, S Sam, van Vollenhoven, Ronald, Nived, Ola, Jönsen, Andreas, Kamen, Diane L, Aranow, Cynthia, Sánchez-Guerrero, Jorge, Gladman, Dafna D, Fortin, Paul R, Alarcon, Graciela S, Merrill, Joan T, Kalunian, Kenneth, Ramos-Casals, Manuel, Steinsson, Kristjan, Zoma, A, Askanase, Anca D, Khamashta, Munther, Bruce, Ian N, Inanc, Murat, Lukusa, Luck, and Bernatsky, Sasha
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Biomedical and Clinical Sciences ,Ophthalmology and Optometry ,Aging ,Prevention ,Autoimmune Disease ,Lupus ,Clinical Research ,Eye Disease and Disorders of Vision ,Evaluation of treatments and therapeutic interventions ,6.1 Pharmaceuticals ,Eye ,Good Health and Well Being ,Humans ,Female ,Aged ,Male ,Hydroxychloroquine ,Antirheumatic Agents ,Lupus Erythematosus ,Systemic ,Retinal Diseases ,Chloroquine ,epidemiology ,lupus erythematosus ,systemic ,outcome assessment ,health care ,lupus erythematosus ,systemic ,outcome assessment ,health care ,Clinical sciences ,Immunology - Abstract
ObjectiveTo evaluate hydroxychloroquine (HCQ)-related retinal toxicity in the Systemic Lupus International Collaborating Clinics (SLICC) inception cohort.MethodsData were collected at annual study visits between 1999 and 2019. We followed patients with incident SLE from first visit on HCQ (time zero) up to time of retinal toxicity (outcome), death, loss-to-follow-up or end of study. Potential retinal toxicity was identified from SLICC Damage Index scores; cases were confirmed with chart review. Using cumulative HCQ duration as the time axis, we constructed univariate Cox regression models to assess if covariates (ie, HCQ daily dose/kg, sex, race/ethnicity, age at SLE onset, education, body mass index, renal damage, chloroquine use) were associated with HCQ-related retinal toxicity.ResultsWe studied 1460 patients (89% female, 52% white). Retinal toxicity was confirmed in 11 patients (incidence 1.0 per 1000 person-years, 0.8% overall). Average cumulative time on HCQ in those with retinal toxicity was 7.4 (SD 3.2) years; the first case was detected 4 years after HCQ initiation. Risk of retinal toxicity was numerically higher in older patients at SLE diagnosis (univariate HR 1.05, 95% CI 1.01 to 1.09).ConclusionsThis is the first assessment of HCQ and retinal disease in incident SLE. We did not see any cases of retinopathy within the first 4 years of HCQ. Cumulative HCQ may be associated with increased risk. Ophthalmology monitoring (and formal assessment of cases of potential toxicity, by a retinal specialist) remains important, especially in patients on HCQ for 10+ years, those needing higher doses and those of older age at SLE diagnosis.
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- 2022
4. Longitudinal analysis of ANA in the Systemic Lupus International Collaborating Clinics (SLICC) Inception Cohort
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Choi, May Yee, Clarke, Ann Elaine, Urowitz, Murray, Hanly, John, St-Pierre, Yvan, Gordon, Caroline, Bae, Sang-Cheol, Romero-Diaz, Juanita, Sanchez-Guerrero, Jorge, Bernatsky, Sasha, Wallace, Daniel J, Isenberg, David, Rahman, Anisur, Merrill, Joan T, Fortin, Paul R, Gladman, Dafna D, Bruce, Ian N, Petri, Michelle, Ginzler, Ellen M, Dooley, Mary Anne, Ramsey-Goldman, Rosalind, Manzi, Susan, Jönsen, Andreas, Alarcón, Graciela S, van Vollenhoven, Ronald F, Aranow, Cynthia, Mackay, Meggan, Ruiz-Irastorza, Guillermo, Lim, Sam, Inanc, Murat, Kalunian, Ken, Jacobsen, Søren, Peschken, Christine, Kamen, Diane L, Askanase, Anca, Buyon, Jill P, Costenbader, Karen H, and Fritzler, Marvin J
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Biomedical and Clinical Sciences ,Clinical Sciences ,Autoimmune Disease ,Lupus ,Antibodies ,Antinuclear ,Autoantibodies ,Cross-Sectional Studies ,Fluorescent Antibody Technique ,Indirect ,Humans ,Lupus Erythematosus ,Systemic ,Systemic Lupus Erythematosus ,Autoimmunity ,Immunology ,Public Health and Health Services ,Arthritis & Rheumatology ,Clinical sciences - Abstract
ObjectivesA perception derived from cross-sectional studies of small systemic lupus erythematosus (SLE) cohorts is that there is a marked discrepancy between antinuclear antibody (ANA) assays, which impacts on clinicians' approach to diagnosis and follow-up. We compared three ANA assays in a longitudinal analysis of a large international incident SLE cohort retested regularly and followed for 5 years.MethodsDemographic, clinical and serological data was from 805 SLE patients at enrolment, year 3 and 5. Two HEp-2 indirect immunofluorescence assays (IFA1, IFA2), an ANA ELISA, and SLE-related autoantibodies were performed in one laboratory. Frequencies of positivity, titres or absorbance units (AU), and IFA patterns were compared using McNemar, Wilcoxon and kappa statistics, respectively.ResultsAt enrolment, ANA positivity (≥1:80) was 96.1% by IFA1 (median titre 1:1280 (IQR 1:640-1:5120)), 98.3% by IFA2 (1:2560 (IQR 1:640-1:5120)) and 96.6% by ELISA (176.3 AU (IQR 106.4 AU-203.5 AU)). At least one ANA assay was positive for 99.6% of patients at enrolment. At year 5, ANA positivity by IFAs (IFA1 95.2%; IFA2 98.9%) remained high, while there was a decrease in ELISA positivity (91.3%, p91% agreement in ANA positivity at all time points and ≥71% agreement in IFA patterns between IFA1 and IFA2.ConclusionIn recent-onset SLE, three ANA assays demonstrated commutability with a high proportion of positivity and titres or AU. However, over 5 years follow-up, there was modest variation in ANA assay performance. In clinical situations where the SLE diagnosis is being considered, a negative test by either the ELISA or HEp-2 IFA may require reflex testing.
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- 2022
5. OMERACT systemic lupus erythematosus domain survey
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Nielsen, Wils, Strand, Vibeke, Simon, Lee, Pinsker, Ellie, Bonilla, Dennisse, Morand, Eric, Thumboo, Julian, Aringer, Martin, Mosca, Marta, Bruce, Ian, Parodis, Ioannis, Kim, Alfred, Desai, Maya, Enman, Yvonne, Shea, Beverley, Wallace, Daniel J., Chaichian, Yashaar, Navarra, Sandra, Aranow, Cynthia, Mackay, Meggan, Trotter, Kimberly, Tayer-Shifman, Oshrat E., Duarte-García, Alí, Shan Tam, Lai, Ugarte-Gil, Manuel F., Pons-Estel, Guillermo J., Reynolds, John A., Nikpour, Mandana, Hoi, Alberta, Romero-Diaz, Juanita, Aggarwal, Amita, Mok, Chi Chiu, Fujio, Keishi, Ramsey-Goldman, Rosalind, Gladman, Dafna D., Arnaud, Laurent, Bultink, Irene E.M., Ruiz-Irastorza, Guillermo, Inês, Luís Sousa, Appenzeller, Simone, Dobrowolski, Chrisanna, Clarke, Ann Elaine, Kamen, Diane L., Barraclough, Michelle, Tani, Chiara, Gómez-Puerta, Jose A, Werth, Victoria P., Katz, Patti, Nowrouzi-Kia, Behdin, Johnson, Sindhu R., Drucker, Aaron M., and Touma, Zahi
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- 2024
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6. Prediction of Hospitalizations in Systemic Lupus Erythematosus Using the Systemic Lupus International Collaborating Clinics Frailty Index
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Legge, Alexandra, Kirkland, Susan, Rockwood, Kenneth, Andreou, Pantelis, Bae, Sang‐Cheol, Gordon, Caroline, Romero‐Diaz, Juanita, Sanchez‐Guerrero, Jorge, Wallace, Daniel J, Bernatsky, Sasha, Clarke, Ann E, Merrill, Joan T, Ginzler, Ellen M, Fortin, Paul R, Gladman, Dafna D, Urowitz, Murray B, Bruce, Ian N, Isenberg, David A, Rahman, Anisur, Alarcón, Graciela S, Petri, Michelle, Khamashta, Munther A, Dooley, MA, Ramsey‐Goldman, Rosalind, Manzi, Susan, Zoma, Asad A, Aranow, Cynthia, Mackay, Meggan, Ruiz‐Irastorza, Guillermo, Lim, S Sam, Inanc, Murat, Vollenhoven, Ronald F, Jonsen, Andreas, Nived, Ola, Ramos‐Casals, Manuel, Kamen, Diane L, Kalunian, Kenneth C, Jacobsen, Søren, Peschken, Christine A, Askanase, Anca, and Hanly, John G
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Epidemiology ,Biomedical and Clinical Sciences ,Health Sciences ,Lupus ,Clinical Research ,Autoimmune Disease ,Inflammatory and immune system ,Good Health and Well Being ,Adult ,Female ,Frailty ,Hospitalization ,Humans ,Immunosuppressive Agents ,Lupus Erythematosus ,Systemic ,Male ,Middle Aged ,Severity of Illness Index ,Young Adult ,Clinical Sciences ,Public Health and Health Services ,Psychology ,Clinical sciences ,Allied health and rehabilitation science - Abstract
ObjectiveThe Systemic Lupus International Collaborating Clinics (SLICC) frailty index (FI) predicts mortality and damage accrual in systemic lupus erythematosus (SLE), but its association with hospitalizations has not been described. Our objective was to estimate the association of baseline SLICC-FI values with future hospitalizations in the SLICC inception cohort.MethodsBaseline SLICC-FI scores were calculated. The number and duration of inpatient hospitalizations during follow-up were recorded. Negative binomial regression was used to estimate the association between baseline SLICC-FI values and the rate of hospitalizations per patient-year of follow-up. Linear regression was used to estimate the association of baseline SLICC-FI scores with the proportion of follow-up time spent in the hospital. Multivariable models were adjusted for relevant baseline characteristics.ResultsThe 1,549 patients with SLE eligible for this analysis were mostly female (88.7%), with a mean ± SD age of 35.7 ± 13.3 years and a median disease duration of 1.2 years (interquartile range 0.9-1.5) at baseline. Mean ± SD baseline SLICC-FI was 0.17 ± 0.08. During mean ± SD follow-up of 7.2 ± 3.7 years, 614 patients (39.6%) experienced 1,570 hospitalizations. Higher baseline SLICC-FI values (per 0.05 increment) were associated with more frequent hospitalizations during follow-up, with an incidence rate ratio of 1.21 (95% confidence interval [95% CI] 1.13-1.30) after adjustment for baseline age, sex, glucocorticoid use, immunosuppressive use, ethnicity/location, SLE Disease Activity Index 2000 score, SLICC/American College of Rheumatology Damage Index score, and disease duration. Among patients with ≥1 hospitalization, higher baseline SLICC-FI values predicted a greater proportion of follow-up time spent hospitalized (relative rate 1.09 [95% CI 1.02-1.16]).ConclusionThe SLICC-FI predicts future hospitalizations among incident SLE patients, further supporting the SLICC-FI as a valid health measure in SLE.
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- 2022
7. Flares after hydroxychloroquine reduction or discontinuation: results from the Systemic Lupus International Collaborating Clinics (SLICC) inception cohort
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Almeida-Brasil, Celline C, Hanly, John G, Urowitz, Murray, Clarke, Ann Elaine, Ruiz-Irastorza, Guillermo, Gordon, Caroline, Ramsey-Goldman, Rosalind, Petri, Michelle, Ginzler, Ellen M, Wallace, DJ, Bae, Sang-Cheol, Romero-Diaz, Juanita, Dooley, Mary Anne, Peschken, Christine, Isenberg, David, Rahman, Anisur, Manzi, Susan, Jacobsen, Søren, Lim, Sam, van Vollenhoven, Ronald F, Nived, Ola, Jönsen, Andreas, Kamen, Diane L, Aranow, Cynthia, Sanchez-Guerrero, Jorge, Gladman, Dafna D, Fortin, Paul R, Alarcón, Graciela S, Merrill, Joan T, Kalunian, Kenneth, Ramos-Casals, Manuel, Steinsson, Kristján, Zoma, Asad, Askanase, Anca, Khamashta, Munther A, Bruce, Ian N, Inanc, Murat, Abrahamowicz, Michal, and Bernatsky, Sasha
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Biomedical and Clinical Sciences ,Clinical Sciences ,Lupus ,Autoimmune Disease ,Clinical Research ,6.1 Pharmaceuticals ,Evaluation of treatments and therapeutic interventions ,Adult ,Antirheumatic Agents ,Drug Tapering ,Female ,Follow-Up Studies ,Humans ,Hydroxychloroquine ,Lupus Erythematosus ,Systemic ,Male ,Middle Aged ,Prospective Studies ,Symptom Flare Up ,Treatment Outcome ,autoimmune diseases ,epidemiology ,hydroxychloroquine ,systemic lupus erythematosus ,Immunology ,Public Health and Health Services ,Arthritis & Rheumatology ,Clinical sciences - Abstract
ObjectivesTo evaluate systemic lupus erythematosus (SLE) flares following hydroxychloroquine (HCQ) reduction or discontinuation versus HCQ maintenance.MethodsWe analysed prospective data from the Systemic Lupus International Collaborating Clinics (SLICC) cohort, enrolled from 33 sites within 15 months of SLE diagnosis and followed annually (1999-2019). We evaluated person-time contributed while on the initial HCQ dose ('maintenance'), comparing this with person-time contributed after a first dose reduction, and after a first HCQ discontinuation. We estimated time to first flare, defined as either subsequent need for therapy augmentation, increase of ≥4 points in the SLE Disease Activity Index-2000, or hospitalisation for SLE. We estimated adjusted HRs (aHRs) with 95% CIs associated with reducing/discontinuing HCQ (vs maintenance). We also conducted separate multivariable hazard regressions in each HCQ subcohort to identify factors associated with flare.ResultsWe studied 1460 (90% female) patients initiating HCQ. aHRs for first SLE flare were 1.20 (95% CI 1.04 to 1.38) and 1.56 (95% CI 1.31 to 1.86) for the HCQ reduction and discontinuation groups, respectively, versus HCQ maintenance. Patients with low educational level were at particular risk of flaring after HCQ discontinuation (aHR 1.43, 95% CI 1.09 to 1.87). Prednisone use at time-zero was associated with over 1.5-fold increase in flare risk in all HCQ subcohorts.ConclusionsSLE flare risk was higher after HCQ taper/discontinuation versus HCQ maintenance. Decisions to maintain, reduce or stop HCQ may affect specific subgroups differently, including those on prednisone and/or with low education. Further study of special groups (eg, seniors) may be helpful.
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- 2022
8. Mycophenolate mofetil withdrawal in patients with systemic lupus erythematosus: a multicentre, open-label, randomised controlled trial
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Chakravarty, Eliza F, Utset, Tammy, Kamen, Diane L, Contreras, Gabriel, McCune, W Joseph, Aranow, Cynthia, Kalunian, Kenneth, Massarotti, Elena, Clowse, Megan E B, Rovin, Brad H, Lim, S Sam, Majithia, Vikas, Dall'Era, Maria, Looney, R John, Erkan, Doruk, Saxena, Amit, Olsen, Nancy J, Ko, Kichul, Guthridge, Joel M, Goldmuntz, Ellen, Springer, Jessica, D'Aveta, Carla, Keyes-Elstein, Lynette, Barry, Bill, Pinckney, Ashley, McNamara, James, and James, Judith A
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- 2024
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9. Impact of glucocorticoids on the incidence of lupus-related major organ damage: a systematic literature review and meta-regression analysis of longitudinal observational studies
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Ugarte-Gil, Manuel Francisco, Mak, Anselm, Leong, Joanna, Dharmadhikari, Bhushan, Kow, Nien Yee, Reátegui-Sokolova, Cristina, Elera-Fitzcarrald, Claudia, Aranow, Cinthia, Arnaud, Laurent, Askanase, Anca D, Bae, Sang-Cheol, Bernatsky, Sasha, Bruce, Ian N, Buyon, Jill, Costedoat-Chalumeau, Nathalie, Dooley, Mary Ann, Fortin, Paul R, Ginzler, Ellen M, Gladman, Dafna D, Hanly, John, Inanc, Murat, Isenberg, David, Jacobsen, Soren, James, Judith A, Jönsen, Andreas, Kalunian, Kenneth, Kamen, Diane L, Lim, Sung Sam, Morand, Eric, Mosca, Marta, Peschken, Christine, Pons-Estel, Bernardo A, Rahman, Anisur, Ramsey-Goldman, Rosalind, Reynolds, John, Romero-Diaz, Juanita, Ruiz-Irastorza, Guillermo, Sánchez-Guerrero, Jorge, Svenungsson, Elisabet, Urowitz, Murray, Vinet, Evelyne, van Vollenhoven, Ronald F, Voskuyl, Alexandre, Wallace, Daniel J, Petri, Michelle A, Manzi, Susan, Clarke, Ann Elaine, Cheung, Mike, Farewell, Vernon, and Alarcon, Graciela S
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Biomedical and Clinical Sciences ,Clinical Sciences ,Autoimmune Disease ,Lupus ,6.1 Pharmaceuticals ,Evaluation of treatments and therapeutic interventions ,Inflammatory and immune system ,Female ,Glucocorticoids ,Humans ,Incidence ,Longitudinal Studies ,Lupus Erythematosus ,Systemic ,Observational Studies as Topic ,Regression Analysis ,glucocorticoids ,outcome assessment ,health care ,lupus erythematosus ,systemic ,Clinical sciences ,Immunology - Abstract
In systemic lupus erythematosus (SLE), disease activity and glucocorticoid (GC) exposure are known to contribute to irreversible organ damage. We aimed to examine the association between GC exposure and organ damage occurrence. We conducted a literature search (PubMed (Medline), Embase and Cochrane January 1966-October 2021). We identified original longitudinal observational studies reporting GC exposure as the proportion of users and/or GC use with dose information as well as the occurrence of new major organ damage as defined in the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index. Meta-regression analyses were performed. Reviews, case-reports and studies with
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- 2021
10. Neuropsychiatric Events in Systemic Lupus Erythematosus: Predictors of Occurrence and Resolution in a Longitudinal Analysis of an International Inception Cohort
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Hanly, John G, Gordon, Caroline, Bae, Sang‐Cheol, Romero‐Diaz, Juanita, Sanchez‐Guerrero, Jorge, Bernatsky, Sasha, Clarke, Ann E, Wallace, Daniel J, Isenberg, David A, Rahman, Anisur, Merrill, Joan T, Fortin, Paul R, Gladman, Dafna D, Urowitz, Murray B, Bruce, Ian N, Petri, Michelle, Ginzler, Ellen M, Dooley, MA, Ramsey‐Goldman, Rosalind, Manzi, Susan, Jonsen, Andreas, Alarcón, Graciela S, Vollenhoven, Ronald F, Aranow, Cynthia, Mackay, Meggan, Ruiz‐Irastorza, Guillermo, Lim, S Sam, Inanc, Murat, Kalunian, Kenneth C, Jacobsen, Soren, Peschken, Christine A, Kamen, Diane L, Askanase, Anca, and Farewell, Vernon
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Biomedical and Clinical Sciences ,Clinical Sciences ,Autoimmune Disease ,Clinical Research ,Lupus ,6.1 Pharmaceuticals ,Evaluation of treatments and therapeutic interventions ,Inflammatory and immune system ,Adult ,Female ,Headache ,Humans ,Longitudinal Studies ,Lupus Erythematosus ,Systemic ,Male ,Middle Aged ,Models ,Theoretical ,Prospective Studies ,Quality of Life ,Sex Factors ,Young Adult ,Immunology ,Public Health and Health Services ,Arthritis & Rheumatology ,Clinical sciences - Abstract
ObjectiveTo determine predictors of change in neuropsychiatric (NP) event status in a large, prospective, international inception cohort of patients with systemic lupus erythematosus (SLE).MethodsUpon enrollment and annually thereafter, NP events attributed to SLE and non-SLE causes and physician-determined resolution were documented. Factors potentially associated with the onset and resolution of NP events were determined by time-to-event analysis using a multistate modeling structure.ResultsNP events occurred in 955 (52.3%) of 1,827 patients, and 593 (31.0%) of 1,910 unique events were attributed to SLE. For SLE-associated NP (SLE NP) events, multivariate analysis revealed a positive association with male sex (P = 0.028), concurrent non-SLE NP events excluding headache (P < 0.001), active SLE (P = 0.012), and glucocorticoid use (P = 0.008). There was a negative association with Asian race (P = 0.002), postsecondary education (P = 0.001), and treatment with immunosuppressive drugs (P = 0.019) or antimalarial drugs (P = 0.056). For non-SLE NP events excluding headache, there was a positive association with concurrent SLE NP events (P < 0.001) and a negative association with African race (P = 0.012) and Asian race (P < 0.001). NP events attributed to SLE had a higher resolution rate than non-SLE NP events, with the exception of headache, which had comparable resolution rates. For SLE NP events, multivariate analysis revealed that resolution was more common in patients of Asian race (P = 0.006) and for central/focal NP events (P < 0.001). For non-SLE NP events, resolution was more common in patients of African race (P = 0.017) and less common in patients who were older at SLE diagnosis (P < 0.001).ConclusionIn a large and long-term study of the occurrence and resolution of NP events in SLE, we identified subgroups with better and worse prognosis. The course of NP events differs greatly depending on their nature and attribution.
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- 2021
11. Cancer Risk in a Large Inception Systemic Lupus Erythematosus Cohort: Effects of Demographic Characteristics, Smoking, and Medications
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Bernatsky, Sasha, Ramsey‐Goldman, Rosalind, Urowitz, Murray B, Hanly, John G, Gordon, Caroline, Petri, Michelle A, Ginzler, Ellen M, Wallace, Daniel J, Bae, Sang‐Cheol, Romero‐Diaz, Juanita, Dooley, Mary Anne, Peschken, Christine A, Isenberg, David A, Rahman, Anisur, Manzi, Susan, Jacobsen, Søren, Lim, S Sam, Vollenhoven, Ronald, Nived, Ola, Kamen, Diane L, Aranow, Cynthia, Ruiz‐Irastorza, Guillermo, Sánchez‐Guerrero, Jorge, Gladman, Dafna D, Fortin, Paul R, Alarcón, Graciela S, Merrill, Joan T, Kalunian, Kenneth C, Ramos‐Casals, Manuel, Steinsson, Kristjan, Zoma, Asad, Askanase, Anca, Khamashta, Munther A, Bruce, Ian, Inanc, Murat, and Clarke, Ann E
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Health Services and Systems ,Biomedical and Clinical Sciences ,Health Sciences ,Oncology and Carcinogenesis ,Clinical Research ,Autoimmune Disease ,Prevention ,Lung ,Patient Safety ,Lung Cancer ,Lupus ,Rare Diseases ,Cancer ,Evaluation of treatments and therapeutic interventions ,6.1 Pharmaceuticals ,Good Health and Well Being ,Adult ,Antimalarials ,Female ,Humans ,Immunosuppressive Agents ,Lupus Erythematosus ,Systemic ,Male ,Middle Aged ,Neoplasms ,Risk Factors ,Smoking ,Clinical Sciences ,Public Health and Health Services ,Psychology ,Clinical sciences ,Allied health and rehabilitation science - Abstract
ObjectiveTo assess cancer risk factors in incident systemic lupus erythematosus (SLE).MethodsClinical variables and cancer outcomes were assessed annually among incident SLE patients. Multivariate hazard regression models (overall risk and most common cancers) included demographic characteristics and time-dependent medications (corticosteroids, antimalarial drugs, immunosuppressants), smoking, and the adjusted mean Systemic Lupus Erythematosus Disease Activity Index 2000 score.ResultsAmong 1,668 patients (average 9 years follow-up), 65 cancers occurred: 15 breast, 10 nonmelanoma skin, 7 lung, 6 hematologic, 6 prostate, 5 melanoma, 3 cervical, 3 renal, 2 each gastric, head and neck, and thyroid, and 1 each rectal, sarcoma, thymoma, and uterine cancers. Half of the cancers (including all lung cancers) occurred in past/current smokers, versus one-third of patients without cancer. Multivariate analyses indicated that overall cancer risk was related primarily to male sex and older age at SLE diagnosis. In addition, smoking was associated with lung cancer. For breast cancer risk, age was positively associated and antimalarial drugs were negatively associated. Antimalarial drugs and higher disease activity were also negatively associated with nonmelanoma skin cancer risk, whereas age and cyclophosphamide were positively associated. Disease activity was associated positively with hematologic and negatively with nonmelanoma skin cancer risk.ConclusionSmoking is a key modifiable risk factor, especially for lung cancer, in SLE. Immunosuppressive medications were not clearly associated with higher risk except for cyclophosphamide and nonmelanoma skin cancer. Antimalarials were negatively associated with breast cancer and nonmelanoma skin cancer risk. SLE activity was associated positively with hematologic cancer and negatively with nonmelanoma skin cancer. Since the absolute number of cancers was small, additional follow-up will help consolidate these findings.
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- 2021
12. Lower vitamin D is associated with metabolic syndrome and insulin resistance in systemic lupus: data from an international inception cohort.
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Chew, Christine, Reynolds, John A, Lertratanakul, Apinya, Wu, Peggy, Urowitz, Murray, Gladman, Dafna D, Fortin, Paul R, Bae, Sang-Cheol, Gordon, Caroline, Clarke, Ann E, Bernatsky, Sasha, Hanly, John G, Isenberg, David, Rahman, Anisur, Sanchez-Guerrero, Jorge, Romero-Diaz, Juanita, Merrill, Joan, Wallace, Daniel, Ginzler, Ellen, Khamashta, Munther, Nived, Ola, Jönsen, Andreas, Steinsson, Kristjan, Manzi, Susan, Kalunian, Ken, Dooley, Mary Anne, Petri, Michelle, Aranow, Cynthia, van Vollenhoven, Ronald, Stoll, Thomas, Alarcón, Graciela S, Lim, S Sam, Ruiz-Irastorza, Guillermo, Peschken, Christine A, Askanase, Anca D, Kamen, Diane L, İnanç, Murat, Ramsey-Goldman, Rosalind, and Bruce, Ian N
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Cardiovascular ,Diabetes ,Clinical Research ,Autoimmune Disease ,Lupus ,Nutrition ,Metabolic and endocrine ,Adult ,Cohort Studies ,Cross-Sectional Studies ,Female ,Global Health ,Humans ,Insulin Resistance ,Lupus Erythematosus ,Systemic ,Male ,Metabolic Syndrome ,Vitamin D ,Vitamin D Deficiency ,Young Adult ,systemic lupus erythematosus ,vitamin D ,cardiovascular disease ,epidemiology ,Clinical Sciences ,Immunology ,Public Health and Health Services ,Arthritis & Rheumatology - Abstract
ObjectivesVitamin D (25(OH)D) deficiency and metabolic syndrome (MetS) may both contribute to increased cardiovascular risk in SLE. We aimed to examine the association of demographic factors, SLE phenotype, therapy and vitamin D levels with MetS and insulin resistance.MethodsThe Systemic Lupus International Collaborating Clinics (SLICC) enrolled patients recently diagnosed with SLE (
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- 2021
13. Safety of procuring research tissue during a clinically indicated kidney biopsy from patients with lupus: data from the Accelerating Medicines Partnership RA/SLE Network.
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Deonaraine, Kristina K, Carlucci, Philip M, Fava, Andrea, Li, Jessica, Wofsy, David, James, Judith A, Putterman, Chaim, Diamond, Betty, Davidson, Anne, Fine, Derek M, Monroy-Trujillo, Jose, Atta, Mohamed G, Haag, Kristin, Rao, Deepak A, Apruzzese, William, Belmont, H Michael, Izmirly, Peter M, Wu, Ming, Connery, Sean, Payan-Schober, Fernanda, Furie, Richard A, Berthier, Celine C, Dall'Era, Maria, Cho, Kerry, Kamen, Diane L, Kalunian, Kenneth, Anolik, Jennifer, Ishimori, Mariko, Weisman, Michael H, Accelerating Medicines Partnership RA/SLE network, Petri, Michelle A, and Buyon, Jill P
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Accelerating Medicines Partnership RA/SLE network ,autoimmunity ,lupus erythematosus ,lupus nephritis ,systemic - Abstract
ObjectivesIn lupus nephritis the pathological diagnosis from tissue retrieved during kidney biopsy drives treatment and management. Despite recent approval of new drugs, complete remission rates remain well under aspirational levels, necessitating identification of new therapeutic targets by greater dissection of the pathways to tissue inflammation and injury. This study assessed the safety of kidney biopsies in patients with SLE enrolled in the Accelerating Medicines Partnership, a consortium formed to molecularly deconstruct nephritis.Methods475 patients with SLE across 15 clinical sites in the USA consented to obtain tissue for research purposes during a clinically indicated kidney biopsy. Adverse events (AEs) were documented for 30 days following the procedure and were determined to be related or unrelated by all site investigators. Serious AEs were defined according to the National Institutes of Health reporting guidelines.Results34 patients (7.2%) experienced a procedure-related AE: 30 with haematoma, 2 with jets, 1 with pain and 1 with an arteriovenous fistula. Eighteen (3.8%) experienced a serious AE requiring hospitalisation; four patients (0.8%) required a blood transfusion related to the kidney biopsy. At one site where the number of cores retrieved during the biopsy was recorded, the mean was 3.4 for those who experienced a related AE (n=9) and 3.07 for those who did not experience any AE (n=140). All related AEs resolved.ConclusionsProcurement of research tissue should be considered feasible, accompanied by a complication risk likely no greater than that incurred for standard clinical purposes. In the quest for targeted treatments personalised based on molecular findings, enhanced diagnostics beyond histology will likely be required.
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- 2021
14. Prediction of Damage Accrual in Systemic Lupus Erythematosus Using the Systemic Lupus International Collaborating Clinics Frailty Index
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Legge, Alexandra, Kirkland, Susan, Rockwood, Kenneth, Andreou, Pantelis, Bae, Sang‐Cheol, Gordon, Caroline, Romero‐Diaz, Juanita, Sanchez‐Guerrero, Jorge, Wallace, Daniel J, Bernatsky, Sasha, Clarke, Ann E, Merrill, Joan T, Ginzler, Ellen M, Fortin, Paul R, Gladman, Dafna D, Urowitz, Murray B, Bruce, Ian N, Isenberg, David A, Rahman, Anisur, Alarcón, Graciela S, Petri, Michelle, Khamashta, Munther A, Dooley, MA, Ramsey‐Goldman, Rosalind, Manzi, Susan, Zoma, Asad A, Aranow, Cynthia, Mackay, Meggan, Ruiz‐Irastorza, Guillermo, Lim, S Sam, Inanc, Murat, Vollenhoven, Ronald F, Jonsen, Andreas, Nived, Ola, Ramos‐Casals, Manuel, Kamen, Diane L, Kalunian, Kenneth C, Jacobsen, Soren, Peschken, Christine A, Askanase, Anca, and Hanly, John G
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Autoimmune Disease ,Lupus ,Evaluation of treatments and therapeutic interventions ,6.1 Pharmaceuticals ,Inflammatory and immune system ,Good Health and Well Being ,Adult ,Disease Progression ,Female ,Frailty ,Humans ,Immunosuppressive Agents ,Lupus Erythematosus ,Systemic ,Male ,Middle Aged ,Quality of Life ,Severity of Illness Index ,Young Adult ,Clinical Sciences ,Immunology ,Public Health and Health Services ,Arthritis & Rheumatology - Abstract
ObjectiveThe Systemic Lupus International Collaborating Clinics (SLICC) frailty index (FI) has been shown to predict mortality, but its association with other important outcomes is unknown. We examined the association of baseline SLICC FI values with damage accrual in the SLICC inception cohort.MethodsThe baseline visit was defined as the first visit at which both organ damage (SLICC/American College of Rheumatology Damage Index [SDI]) and health-related quality of life (Short Form 36) were assessed. Baseline SLICC FI scores were calculated. Damage accrual was measured by the increase in SDI between the baseline assessment and the last study visit. Multivariable negative binomial regression was used to estimate the association between baseline SLICC FI values and the rate of increase in the SDI during follow-up, adjusting for relevant demographic and clinical characteristics.ResultsThe 1,549 systemic lupus erythematosus (SLE) patients eligible for this analysis were mostly female (88.7%) with a mean ± SD age of 35.7 ± 13.3 years and a median disease duration of 1.2 years (interquartile range 0.9-1.5 years) at baseline. The mean ± SD baseline SLICC FI was 0.17 ± 0.08. Over a mean ± SD follow-up of 7.2 ± 3.7 years, 653 patients (42.2%) had an increase in SDI. Higher baseline SLICC FI values (per 0.05 increase) were associated with higher rates of increase in the SDI during follow-up (incidence rate ratio [IRR] 1.19 [95% confidence interval 1.13-1.25]), after adjusting for age, sex, ethnicity/region, education, baseline SLE Disease Activity Index 2000, baseline SDI, and baseline use of glucocorticoids, antimalarials, and immunosuppressive agents.ConclusionOur findings indicate that the SLICC FI predicts damage accrual in incident SLE, which further supports the SLICC FI as a valid health measure in SLE.
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- 2020
15. Peripheral Nervous System Disease in Systemic Lupus Erythematosus: Results From an International Inception Cohort Study
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Hanly, John G, Li, Qiuju, Su, Li, Urowitz, Murray B, Gordon, Caroline, Bae, Sang‐Cheol, Romero‐Diaz, Juanita, Sanchez‐Guerrero, Jorge, Bernatsky, Sasha, Clarke, Ann E, Wallace, Daniel J, Isenberg, David A, Rahman, Anisur, Merrill, Joan T, Fortin, Paul R, Gladman, Dafna D, Bruce, Ian N, Petri, Michelle, Ginzler, Ellen M, Dooley, MA, Steinsson, Kristjan, Ramsey‐Goldman, Rosalind, Zoma, Asad A, Manzi, Susan, Nived, Ola, Jonsen, Andreas, Khamashta, Munther A, Alarcón, Graciela S, Svenungsson, Elisabet, Vollenhoven, Ronald F, Aranow, Cynthia, Mackay, Meggan, Ruiz‐Irastorza, Guillermo, Ramos‐Casals, Manuel, Lim, S Sam, Inanc, Murat, Kalunian, Kenneth C, Jacobsen, Soren, Peschken, Christine A, Kamen, Diane L, Askanase, Anca, Theriault, Chris, and Farewell, Vernon
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Biomedical and Clinical Sciences ,Clinical Sciences ,Chronic Pain ,Neurosciences ,Pain Research ,Clinical Research ,Neurodegenerative ,Lupus ,Peripheral Neuropathy ,Autoimmune Disease ,6.1 Pharmaceuticals ,Evaluation of treatments and therapeutic interventions ,Inflammatory and immune system ,Neurological ,Good Health and Well Being ,Adult ,Age Factors ,Cohort Studies ,Cranial Nerve Diseases ,Female ,Humans ,Lupus Erythematosus ,Systemic ,Lupus Vasculitis ,Central Nervous System ,Male ,Middle Aged ,Mononeuropathies ,Multivariate Analysis ,Peripheral Nervous System Diseases ,Proportional Hazards Models ,Severity of Illness Index ,Young Adult ,Immunology ,Public Health and Health Services ,Arthritis & Rheumatology ,Clinical sciences - Abstract
ObjectiveTo determine the frequency, clinical characteristics, associations, and outcomes of different types of peripheral nervous system (PNS) disease in a multiethnic/multiracial, prospective inception cohort of systemic lupus erythematosus (SLE) patients.MethodsPatients were evaluated annually for 19 neuropsychiatric (NP) events including 7 types of PNS disease. SLE disease activity, organ damage, autoantibodies, and patient and physician assessment of outcome were measured. Time to event and linear regressions were used as appropriate.ResultsOf 1,827 SLE patients, 88.8% were female, and 48.8% were white. The mean ± SD age was 35.1 ± 13.3 years, disease duration at enrollment was 5.6 ± 4.2 months, and follow-up was 7.6 ± 4.6 years. There were 161 PNS events in 139 (7.6%) of 1,827 patients. The predominant events were peripheral neuropathy (66 of 161 [41.0%]), mononeuropathy (44 of 161 [27.3%]), and cranial neuropathy (39 of 161 [24.2%]), and the majority were attributed to SLE. Multivariate Cox regressions suggested longer time to resolution in patients with a history of neuropathy, older age at SLE diagnosis, higher SLE Disease Activity Index 2000 scores, and for peripheral neuropathy versus other neuropathies. Neuropathy was associated with significantly lower Short Form 36 (SF-36) physical and mental component summary scores versus no NP events. According to physician assessment, the majority of neuropathies resolved or improved over time, which was associated with improvements in SF-36 summary scores for peripheral neuropathy and mononeuropathy.ConclusionPNS disease is an important component of total NPSLE and has a significant negative impact on health-related quality of life. The outcome is favorable for most patients, but our findings indicate that several factors are associated with longer time to resolution.
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- 2020
16. Construction of a Frailty Index as a Novel Health Measure in Systemic Lupus Erythematosus
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Legge, Alexandra, Kirkland, Susan, Rockwood, Kenneth, Andreou, Pantelis, Bae, Sang-Cheol, Gordon, Caroline, Romero-Diaz, Juanita, Sanchez-Guerrero, Jorge, Wallace, Daniel J, Bernatsky, Sasha, Clarke, Ann E, Merrill, Joan T, Ginzler, Ellen M, Fortin, Paul, Gladman, Dafna D, Urowitz, Murray B, Bruce, Ian N, Isenberg, David A, Rahman, Anisur, Alarcón, Graciela S, Petri, Michelle, Khamashta, Munther A, Dooley, MA, Ramsey-Goldman, Rosalind, Manzi, Susan, Zoma, Asad A, Aranow, Cynthia, Mackay, Meggan, Ruiz-Irastorza, Guillermo, Lim, S Sam, Inanc, Murat, van Vollenhoven, Ronald F, Jonsen, Andreas, Nived, Ola, Ramos-Casals, Manuel, Kamen, Diane L, Kalunian, Kenneth C, Jacobsen, Soren, Peschken, Christine A, Askanase, Anca, and Hanly, John G
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Biomedical and Clinical Sciences ,Clinical Sciences ,Clinical Research ,Autoimmune Disease ,Lupus ,6.1 Pharmaceuticals ,Evaluation of treatments and therapeutic interventions ,Inflammatory and immune system ,Adult ,Female ,Frailty ,Humans ,Longitudinal Studies ,Lupus Erythematosus ,Systemic ,Male ,Middle Aged ,Patient Outcome Assessment ,Prevalence ,Severity of Illness Index ,Young Adult ,SYSTEMIC LUPUS ERYTHEMATOSUS ,OUTCOME ASSESSMENT ,COHORT STUDIES ,Immunology ,Public Health and Health Services ,Arthritis & Rheumatology ,Clinical sciences - Abstract
ObjectiveTo construct a Frailty Index (FI) as a measure of vulnerability to adverse outcomes among patients with systemic lupus erythematosus (SLE), using data from the Systemic Lupus International Collaborating Clinics (SLICC) inception cohort.MethodsThe SLICC inception cohort consists of recently diagnosed patients with SLE followed annually with clinical and laboratory assessments. For this analysis, the baseline visit was defined as the first study visit at which sufficient information was available for construction of an FI. Following a standard procedure, variables from the SLICC database were evaluated as potential health deficits. Selected health deficits were then used to generate a SLICC-FI. The prevalence of frailty in the baseline dataset was evaluated using established cutpoints for FI values.ResultsThe 1683 patients with SLE (92.1% of the overall cohort) eligible for inclusion in the baseline dataset were mostly female (89%) with mean (SD) age 35.7 (13.4) years and mean (SD) disease duration 18.8 (15.7) months at baseline. Of 222 variables, 48 met criteria for inclusion in the SLICC-FI. Mean (SD) SLICC-FI was 0.17 (0.08) with a range from 0 to 0.51. At baseline, 27.1% (95% CI 25.0-29.2) of patients were classified as frail, based on SLICC-FI values > 0.21.ConclusionThe SLICC inception cohort permits feasible construction of an FI for use in patients with SLE. Even in a relatively young cohort of patients with SLE, frailty was common. The SLICC-FI may be a useful tool for identifying patients with SLE who are most vulnerable to adverse outcomes, but validation of this index is required prior to its use.
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- 2020
17. Assessing the Costs of Neuropsychiatric Disease in the Systemic Lupus International Collaborating Clinics Cohort Using Multistate Modeling
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Clarke, Ann E., Hanly, John G., Urowitz, Murray B., St. Pierre, Yvan, Gordon, Caroline, Bae, Sang‐Cheol, Romero‐Diaz, Juanita, Sanchez‐Guerrero, Jorge, Bernatsky, Sasha, Wallace, Daniel J., Isenberg, David A., Rahman, Anisur, Merrill, Joan T., Fortin, Paul R., Gladman, Dafna D., Bruce, Ian N., Petri, Michelle, Ginzler, Ellen M., Dooley, Mary Anne, Ramsey‐Goldman, Rosalind, Manzi, Susan, Jönsen, Andreas, Alarcón, Graciela S., Van Vollenhoven, Ronald F., Aranow, Cynthia, Mackay, Meggan, Ruiz‐Irastorza, Guillermo, Lim, S. Sam, Inanc, Murat, Kalunian, Kenneth C., Jacobsen, Soren, Peschken, Christine A., Kamen, Diane L., Askanase, Anca, and Farewell, Vernon
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- 2023
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18. 2019 European League Against Rheumatism/American College of Rheumatology Classification Criteria for Systemic Lupus Erythematosus
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Aringer, Martin, Costenbader, Karen, Daikh, David, Brinks, Ralph, Mosca, Marta, Ramsey‐Goldman, Rosalind, Smolen, Josef S, Wofsy, David, Boumpas, Dimitrios T, Kamen, Diane L, Jayne, David, Cervera, Ricard, Costedoat‐Chalumeau, Nathalie, Diamond, Betty, Gladman, Dafna D, Hahn, Bevra, Hiepe, Falk, Jacobsen, Søren, Khanna, Dinesh, Lerstrøm, Kirsten, Massarotti, Elena, McCune, Joseph, Ruiz‐Irastorza, Guillermo, Sanchez‐Guerrero, Jorge, Schneider, Matthias, Urowitz, Murray, Bertsias, George, Hoyer, Bimba F, Leuchten, Nicolai, Tani, Chiara, Tedeschi, Sara K, Touma, Zahi, Schmajuk, Gabriela, Anic, Branimir, Assan, Florence, Chan, Tak Mao, Clarke, Ann Elaine, Crow, Mary K, Czirják, László, Doria, Andrea, Graninger, Winfried, Halda‐Kiss, Bernadett, Hasni, Sarfaraz, Izmirly, Peter M, Jung, Michelle, Kumánovics, Gábor, Mariette, Xavier, Padjen, Ivan, Pego‐Reigosa, José M, Romero‐Diaz, Juanita, Fernández, Íñigo Rúa‐Figueroa, Seror, Raphaèle, Stummvoll, Georg H, Tanaka, Yoshiya, Tektonidou, Maria G, Vasconcelos, Carlos, Vital, Edward M, Wallace, Daniel J, Yavuz, Sule, Meroni, Pier Luigi, Fritzler, Marvin J, Naden, Ray, Dörner, Thomas, and Johnson, Sindhu R
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Biomedical and Clinical Sciences ,Clinical Sciences ,Lupus ,Autoimmune Disease ,Inflammatory and immune system ,Adult ,Antibodies ,Antinuclear ,Antibodies ,Antiphospholipid ,Autoantibodies ,Cohort Studies ,Complement System Proteins ,Decision Support Techniques ,Delphi Technique ,Europe ,Female ,Humans ,International Cooperation ,Lupus Erythematosus ,Systemic ,Male ,Middle Aged ,Rheumatology ,Sensitivity and Specificity ,Societies ,Medical ,United States ,Immunology ,Public Health and Health Services ,Arthritis & Rheumatology ,Clinical sciences - Abstract
ObjectiveTo develop new classification criteria for systemic lupus erythematosus (SLE) jointly supported by the European League Against Rheumatism (EULAR) and the American College of Rheumatology (ACR).MethodsThis international initiative had four phases. 1) Evaluation of antinuclear antibody (ANA) as an entry criterion through systematic review and meta-regression of the literature and criteria generation through an international Delphi exercise, an early patient cohort, and a patient survey. 2) Criteria reduction by Delphi and nominal group technique exercises. 3) Criteria definition and weighting based on criterion performance and on results of a multi-criteria decision analysis. 4) Refinement of weights and threshold scores in a new derivation cohort of 1,001 subjects and validation compared with previous criteria in a new validation cohort of 1,270 subjects.ResultsThe 2019 EULAR/ACR classification criteria for SLE include positive ANA at least once as obligatory entry criterion; followed by additive weighted criteria grouped in 7 clinical (constitutional, hematologic, neuropsychiatric, mucocutaneous, serosal, musculoskeletal, renal) and 3 immunologic (antiphospholipid antibodies, complement proteins, SLE-specific antibodies) domains, and weighted from 2 to 10. Patients accumulating ≥10 points are classified. In the validation cohort, the new criteria had a sensitivity of 96.1% and specificity of 93.4%, compared with 82.8% sensitivity and 93.4% specificity of the ACR 1997 and 96.7% sensitivity and 83.7% specificity of the Systemic Lupus International Collaborating Clinics 2012 criteria.ConclusionThese new classification criteria were developed using rigorous methodology with multidisciplinary and international input, and have excellent sensitivity and specificity. Use of ANA entry criterion, hierarchically clustered, and weighted criteria reflects current thinking about SLE and provides an improved foundation for SLE research.
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- 2019
19. Evaluating the Properties of a Frailty Index and Its Association With Mortality Risk Among Patients With Systemic Lupus Erythematosus
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Legge, Alexandra, Kirkland, Susan, Rockwood, Kenneth, Andreou, Pantelis, Bae, Sang‐Cheol, Gordon, Caroline, Romero‐Diaz, Juanita, Sanchez‐Guerrero, Jorge, Wallace, Daniel J, Bernatsky, Sasha, Clarke, Ann E, Merrill, Joan T, Ginzler, Ellen M, Fortin, Paul, Gladman, Dafna D, Urowitz, Murray B, Bruce, Ian N, Isenberg, David A, Rahman, Anisur, Alarcón, Graciela S, Petri, Michelle, Khamashta, Munther A, Dooley, MA, Ramsey‐Goldman, Rosalind, Manzi, Susan, Steinsson, Kristjan, Zoma, Asad A, Aranow, Cynthia, Mackay, Meggan, Ruiz‐Irastorza, Guillermo, Lim, S Sam, Inanc, Murat, Vollenhoven, Ronald F, Jonsen, Andreas, Nived, Ola, Ramos‐Casals, Manuel, Kamen, Diane L, Kalunian, Kenneth C, Jacobsen, Soren, Peschken, Christine A, Askanase, Anca, and Hanly, John G
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Biomedical and Clinical Sciences ,Clinical Sciences ,Immunology ,Autoimmune Disease ,Behavioral and Social Science ,Lupus ,6.1 Pharmaceuticals ,Evaluation of treatments and therapeutic interventions ,Inflammatory and immune system ,Good Health and Well Being ,Adult ,Aged ,Female ,Frailty ,Humans ,Lupus Erythematosus ,Systemic ,Male ,Middle Aged ,Proportional Hazards Models ,Quality of Life ,Reproducibility of Results ,Risk Assessment ,Risk Factors ,Severity of Illness Index ,Public Health and Health Services ,Arthritis & Rheumatology ,Clinical sciences - Abstract
ObjectiveTo evaluate the properties of a frailty index (FI), constructed using data from the Systemic Lupus International Collaborating Clinics (SLICC) inception cohort, as a novel health measure in systemic lupus erythematosus (SLE).MethodsFor this secondary analysis, the baseline visit was defined as the first study visit at which both organ damage (SLICC/American College of Rheumatology Damage Index [SDI]) and health-related quality of life (Short-Form 36 [SF-36] scores) were assessed. The SLICC-FI was constructed using baseline data. The SLICC-FI comprises 48 health deficits, including items related to organ damage, disease activity, comorbidities, and functional status. Content, construct, and criterion validity of the SLICC-FI were assessed. Multivariable Cox regression was used to estimate the association between baseline SLICC-FI values and mortality risk, adjusting for demographic and clinical factors.ResultsIn the baseline data set of 1,683 patients with SLE, 89% were female, the mean ± SD age was 35.7 ± 13.4 years, and the mean ± SD disease duration was 18.8 ± 15.7 months. At baseline, the mean ± SD SLICC-FI score was 0.17 ± 0.08 (range 0-0.51). Baseline SLICC-FI values exhibited the expected measurement properties and were weakly correlated with baseline SDI scores (r = 0.26, P < 0.0001). Higher baseline SLICC-FI values (per 0.05 increment) were associated with increased mortality risk (hazard ratio 1.59, 95% confidence interval 1.35-1.87), after adjusting for age, sex, steroid use, ethnicity/region, and baseline SDI scores.ConclusionThe SLICC-FI demonstrates internal validity as a health measure in SLE and might be used to predict future mortality risk. The SLICC-FI is potentially valuable for quantifying vulnerability among patients with SLE, and adds to existing prognostic scores.
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- 2019
20. Use of combined hormonal contraceptives among women with systemic lupus erythematosus with and without medical contraindications to oestrogen
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Mendel, Arielle, Bernatsky, Sasha, Pineau, Christian A, St-Pierre, Yvan, Hanly, John G, Urowitz, Murray B, Clarke, Ann E, Romero-Diaz, Juanita, Gordon, Caroline, Bae, Sang-Cheol, Wallace, Daniel J, Merrill, Joan T, Buyon, Jill, Isenberg, David A, Rahman, Anisur, Ginzler, Ellen M, Petri, Michelle, Dooley, Mary Anne, Fortin, Paul, Gladman, Dafna D, Steinsson, Kristján, Ramsey-Goldman, Rosalind, Khamashta, Munther A, Aranow, Cynthia, Mackay, Meggan, Alarcón, Graciela, Manzi, Susan, Nived, Ola, Jönsen, Andreas, Zoma, Asad A, van Vollenhoven, Ronald F, Ramos-Casals, Manuel, Ruiz-Irastorza, Giuillermo, Lim, Sam, Kalunian, Kenneth C, Inanc, Murat, Kamen, Diane L, Peschken, Christine A, Jacobsen, Søren, Askanase, Anca, Sanchez-Guerrero, Jorge, Bruce, Ian N, Costedoat-Chalumeau, Nathalie, and Vinet, Evelyne
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Contraception/Reproduction ,Clinical Research ,Lupus ,Autoimmune Disease ,Good Health and Well Being ,Adolescent ,Adult ,Antiphospholipid Syndrome ,Cohort Studies ,Contraceptives ,Oral ,Combined ,Contraceptives ,Oral ,Hormonal ,Contraindications ,Drug ,Drug Utilization ,Educational Status ,Female ,Humans ,Hypertension ,Lupus Erythematosus ,Systemic ,Migraine with Aura ,Practice Patterns ,Physicians' ,Registries ,Risk Factors ,Severity of Illness Index ,Young Adult ,systemic lupus erythematosus ,anti-phospholipid syndrome ,contraception ,epidemiology ,Clinical Sciences ,Immunology ,Public Health and Health Services ,Arthritis & Rheumatology - Abstract
ObjectivesTo assess the prevalence of combined hormonal contraceptives (CHCs) in reproductive-age women with SLE with and without possible contraindications and to determine factors associated with their use in the presence of possible contraindications.MethodsThis observational cohort study included premenopausal women ages 18-45 years enrolled in the SLICC Registry ⩽15 months after SLE onset, with annual assessments spanning 2000-2017. World Health Organization Category 3 or 4 contraindications to CHCs (e.g. hypertension, aPL) were assessed at each study visit. High disease activity (SLEDAI score >12 or use of >0.5 mg/kg/day of prednisone) was considered a relative contraindication.ResultsA total of 927 SLE women contributed 6315 visits, of which 3811 (60%) occurred in the presence of one or more possible contraindication to CHCs. Women used CHCs during 512 (8%) visits, of which 281 (55%) took place in the setting of one or more possible contraindication. The most frequently observed contraindications were aPL (52%), hypertension (34%) and migraine with aura (22%). Women with one or more contraindication were slightly less likely to be taking CHCs [7% of visits (95% CI 7, 8)] than women with no contraindications [9% (95% CI 8, 10)].ConclusionCHC use was low compared with general population estimates (>35%) and more than half of CHC users had at least one possible contraindication. Many yet unmeasured factors, including patient preferences, may have contributed to these observations. Further work should also aim to clarify outcomes associated with this exposure.
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- 2019
21. Antinuclear Antibody–Negative Systemic Lupus Erythematosus in an International Inception Cohort
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Choi, May Y, Clarke, Ann E, St. Pierre, Yvan, Hanly, John G, Urowitz, Murray B, Romero‐Diaz, Juanita, Gordon, Caroline, Bae, Sang‐Cheol, Bernatsky, Sasha, Wallace, Daniel J, Merrill, Joan T, Isenberg, David A, Rahman, Anisur, Ginzler, Ellen M, Petri, Michelle, Bruce, Ian N, Dooley, Mary A, Fortin, Paul R, Gladman, Dafna D, Sanchez‐Guerrero, Jorge, Steinsson, Kristjan, Ramsey‐Goldman, Rosalind, Khamashta, Munther A, Aranow, Cynthia, Alarcón, Graciela S, Manzi, Susan, Nived, Ola, Zoma, Asad A, Vollenhoven, Ronald F, Ramos‐Casals, Manuel, Ruiz‐Irastorza, Guillermo, Lim, S Sam, Kalunian, Kenneth C, Inanc, Murat, Kamen, Diane L, Peschken, Christine A, Jacobsen, Soren, Askanase, Anca, Stoll, Thomas, Buyon, Jill, Mahler, Michael, and Fritzler, Marvin J
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Biomedical and Clinical Sciences ,Clinical Sciences ,Lupus ,Autoimmune Disease ,Inflammatory and immune system ,Adult ,Antibodies ,Antinuclear ,Biomarkers ,Female ,Fluorescent Antibody Technique ,Indirect ,Glucocorticoids ,Humans ,Immunosuppressive Agents ,Lupus Erythematosus ,Systemic ,Male ,Mitosis ,Predictive Value of Tests ,Prognosis ,Serologic Tests ,Public Health and Health Services ,Psychology ,Clinical sciences ,Allied health and rehabilitation science - Abstract
ObjectiveThe spectrum of antinuclear antibodies (ANAs) is changing to include both nuclear staining as well as cytoplasmic and mitotic cell patterns (CMPs) and accordingly a change is occurring in terminology to anticellular antibodies. This study examined the prevalence of indirect immunofluorescence (IIF) anticellular antibody staining using the Systemic Lupus International Collaborating Clinics inception cohort.MethodsAnticellular antibodies were detected by IIF on HEp-2000 substrate using the baseline serum. Three serologic subsets were examined: ANA positive (presence of either nuclear or mixed nuclear/CMP staining), anticellular antibody negative (absence of any intracellular staining), and isolated CMP staining. The odds of being anticellular antibody negative versus ANA or isolated CMP positive was assessed by multivariable analysis.ResultsA total of 1,137 patients were included; 1,049 (92.3%) were ANA positive, 71 (6.2%) were anticellular antibody negative, and 17 (1.5%) had an isolated CMP. The isolated CMP-positive group did not differ from the ANA-positive or anticellular antibody-negative groups in clinical, demographic, or serologic features. Patients who were older (odds ratio [OR] 1.02 [95% confidence interval (95% CI) 1.00, 1.04]), of white race/ethnicity (OR 3.53 [95% CI 1.77, 7.03]), or receiving high-dose glucocorticoids at or prior to enrollment (OR 2.39 [95% CI 1.39, 4.12]) were more likely to be anticellular antibody negative. Patients on immunosuppressants (OR 0.35 [95% CI 0.19, 0.64]) or with anti-SSA/Ro 60 (OR 0.41 [95% CI 0.23, 0.74]) or anti-U1 RNP (OR 0.43 [95% CI 0.20, 0.93]) were less likely to be anticellular antibody negative.ConclusionIn newly diagnosed systemic lupus erythematosus, 6.2% of patients were anticellular antibody negative, and 1.5% had an isolated CMP. The prevalence of anticellular antibody-negative systemic lupus erythematosus will likely decrease as emerging nomenclature guidelines recommend that non-nuclear patterns should also be reported as a positive ANA.
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- 2019
22. The immune cell landscape in kidneys of patients with lupus nephritis
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Arazi, Arnon, Rao, Deepak A, Berthier, Celine C, Davidson, Anne, Liu, Yanyan, Hoover, Paul J, Chicoine, Adam, Eisenhaure, Thomas M, Jonsson, A Helena, Li, Shuqiang, Lieb, David J, Zhang, Fan, Slowikowski, Kamil, Browne, Edward P, Noma, Akiko, Sutherby, Danielle, Steelman, Scott, Smilek, Dawn E, Tosta, Patti, Apruzzese, William, Massarotti, Elena, Dall’Era, Maria, Park, Meyeon, Kamen, Diane L, Furie, Richard A, Payan-Schober, Fernanda, Pendergraft, William F, McInnis, Elizabeth A, Buyon, Jill P, Petri, Michelle A, Putterman, Chaim, Kalunian, Kenneth C, Woodle, E Steve, Lederer, James A, Hildeman, David A, Nusbaum, Chad, Raychaudhuri, Soumya, Kretzler, Matthias, Anolik, Jennifer H, Brenner, Michael B, Wofsy, David, Hacohen, Nir, and Diamond, Betty
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Lupus ,Genetics ,Autoimmune Disease ,Kidney Disease ,Clinical Research ,2.1 Biological and endogenous factors ,Underpinning research ,Aetiology ,1.1 Normal biological development and functioning ,Inflammatory and immune system ,Renal and urogenital ,Biomarkers ,Biopsy ,Cluster Analysis ,Computational Biology ,Epithelial Cells ,Flow Cytometry ,Gene Expression Profiling ,Gene Expression Regulation ,Humans ,Immunophenotyping ,Interferons ,Kidney ,Leukocytes ,Lupus Nephritis ,Lymphocytes ,Molecular Sequence Annotation ,Myeloid Cells ,Single-Cell Analysis ,Transcriptome ,Accelerating Medicines Partnership in SLE network ,Immunology - Abstract
Lupus nephritis is a potentially fatal autoimmune disease for which the current treatment is ineffective and often toxic. To develop mechanistic hypotheses of disease, we analyzed kidney samples from patients with lupus nephritis and from healthy control subjects using single-cell RNA sequencing. Our analysis revealed 21 subsets of leukocytes active in disease, including multiple populations of myeloid cells, T cells, natural killer cells and B cells that demonstrated both pro-inflammatory responses and inflammation-resolving responses. We found evidence of local activation of B cells correlated with an age-associated B-cell signature and evidence of progressive stages of monocyte differentiation within the kidney. A clear interferon response was observed in most cells. Two chemokine receptors, CXCR4 and CX3CR1, were broadly expressed, implying a potentially central role in cell trafficking. Gene expression of immune cells in urine and kidney was highly correlated, which would suggest that urine might serve as a surrogate for kidney biopsies.
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- 2019
23. Multicriteria decision analysis process to develop new classification criteria for systemic lupus erythematosus
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Tedeschi, Sara K, Johnson, Sindhu R, Boumpas, Dimitrios T, Daikh, David, Dörner, Thomas, Diamond, Betty, Jacobsen, Søren, Jayne, David, Kamen, Diane L, McCune, W Joseph, Mosca, Marta, Ramsey-Goldman, Rosalind, Ruiz-Irastorza, Guillermo, Schneider, Matthias, Urowitz, Murray, Wofsy, David, Smolen, Josef S, Naden, Raymond P, Aringer, Martin, and Costenbader, Karen H
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Biomedical and Clinical Sciences ,Clinical Sciences ,Immunology ,Autoimmune Disease ,Lupus ,Consensus ,Decision Support Techniques ,Humans ,Lupus Erythematosus ,Systemic ,Reproducibility of Results ,Rheumatology ,clinical research ,methodology ,systemic lupus erythematosus ,Public Health and Health Services ,Arthritis & Rheumatology ,Clinical sciences - Abstract
European League Against Rheumatism and are jointly supporting multiphase development of systemic lupus erythematosus (SLE) classification criteria based on weighted criteria and a continuous probability scale. Prior steps included item generation, item reduction and hierarchical organisation of candidate criteria using an evidence-based approach. Our objectives were to determine relative weights using multicriteria decision analysis (MCDA) and to set a provisional threshold score for SLE classification. An SLE Expert Panel (8 European, 9 North American) submitted 164 real, unique cases with a wide range of SLE probability in a standardised format. Using the candidate criteria, experts scored and rank-ordered 20 representative cases. At an in-person meeting, experts reviewed inter-rater reliability of scoring, further refined criteria definitions and participated in an MCDA exercise. Based on expert consensus decisions on pairwise comparisons of criteria, 1000minds software calculated criteria weights and rank-ordered the remaining 144 cases based on their additive scores. The score of the lowest-ranked case for which complete expert consensus was achieved defined the provisional threshold classification score. Inter-rater reliability of scoring cases with the candidate criteria was good. MCDA involved 74 pairwise decisions and was repeated for the arthritis and mucocutaneous domains when the initial ranking of some cases did not match expert opinion. After criteria weights and additive scores were recalculated once, experts reached consensus for SLE classification for all cases scoring>83. Using an iterative process, the candidate criteria definitions were refined, preliminary weights were calculated and a provisional threshold score for SLE classification was determined.
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- 2019
24. Osteopontin and Disease Activity in Patients with Recent-onset Systemic Lupus Erythematosus: Results from the SLICC Inception Cohort
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Wirestam, Lina, Enocsson, Helena, Skogh, Thomas, Padyukov, Leonid, Jönsen, Andreas, Urowitz, Murray B, Gladman, Dafna D, Romero-Diaz, Juanita, Bae, Sang-Cheol, Fortin, Paul R, Sanchez-Guerrero, Jorge, Clarke, Ann E, Bernatsky, Sasha, Gordon, Caroline, Hanly, John G, Wallace, Daniel, Isenberg, David A, Rahman, Anisur, Merrill, Joan, Ginzler, Ellen, Alarcón, Graciela S, Chatham, W Winn, Petri, Michelle, Khamashta, Munther, Aranow, Cynthia, Mackay, Meggan, Dooley, Mary Anne, Manzi, Susan, Ramsey-Goldman, Rosalind, Nived, Ola, Steinsson, Kristjan, Zoma, Asad, Ruiz-Irastorza, Guillermo, Lim, Sam, Kalunian, Ken, Inanc, Murat, van Vollenhoven, Ronald, Ramos-Casals, Manuel, Kamen, Diane L, Jacobsen, Søren, Peschken, Christine, Askanase, Anca, Stoll, Thomas, Bruce, Ian N, Wetterö, Jonas, and Sjöwall, Christopher
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Biomedical and Clinical Sciences ,Clinical Sciences ,Autoimmune Disease ,Kidney Disease ,Lupus ,Clinical Research ,Inflammatory and immune system ,Adolescent ,Adult ,Age Factors ,Aged ,Asia ,Biomarkers ,Child ,Cross-Sectional Studies ,Disease Progression ,Enzyme-Linked Immunosorbent Assay ,Europe ,Female ,Follow-Up Studies ,Humans ,Internationality ,Logistic Models ,Lupus Erythematosus ,Systemic ,Male ,Middle Aged ,Multivariate Analysis ,North America ,Osteopontin ,Reference Values ,Severity of Illness Index ,Sex Factors ,Young Adult ,SYSTEMIC LUPUS ERYTHEMATOSUS ,BIOMARKERS ,OSTEOPONTIN ,DISEASE ACTIVITY ,ORGAN DAMAGE ,PROGNOSIS ,Immunology ,Public Health and Health Services ,Arthritis & Rheumatology ,Clinical sciences - Abstract
ObjectiveIn cross-sectional studies, elevated osteopontin (OPN) levels have been proposed to reflect, and/or precede, progressive organ damage and disease severity in systemic lupus erythematosus (SLE). We aimed, in a cohort of patients with recent-onset SLE, to determine whether raised serum OPN levels precede damage and/or are associated with disease activity or certain disease phenotypes.MethodsWe included 344 patients from the Systemic Lupus International Collaborating Clinics (SLICC) Inception Cohort who had 5 years of followup data available. All patients fulfilled the 1997 American College of Rheumatology (ACR) criteria. Baseline sera from patients and from age- and sex-matched population-based controls were analyzed for OPN using ELISA. Disease activity and damage were assessed at each annual followup visit using the SLE Disease Activity Index 2000 (SLEDAI-2K) and the SLICC/ACR damage index (SDI), respectively.ResultsCompared to controls, baseline OPN was raised 4-fold in SLE cases (p < 0.0001). After relevant adjustments in a binary logistic regression model, OPN levels failed to significantly predict global damage accrual defined as SDI ≥ 1 at 5 years. However, baseline OPN correlated with SLEDAI-2K at enrollment into the cohort (r = 0.27, p < 0.0001), and patients with high disease activity (SLEDAI-2K ≥ 5) had raised serum OPN (p < 0.0001). In addition, higher OPN levels were found in patients with persistent disease activity (p = 0.0006), in cases with renal involvement (p < 0.0001) and impaired estimated glomerular filtration rate (p = 0.01).ConclusionThe performance of OPN to predict development of organ damage was not impressive. However, OPN associated significantly with lupus nephritis and with raised disease activity at enrollment, as well as over time.
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- 2019
25. Psychosis in Systemic Lupus Erythematosus: Results From an International Inception Cohort Study
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Hanly, John G, Li, Qiuju, Su, Li, Urowitz, Murray B, Gordon, Caroline, Bae, Sang-Cheol, Romero-Diaz, Juanita, Sanchez-Guerrero, Jorge, Bernatsky, Sasha, Clarke, Ann E, Wallace, Daniel J, Isenberg, David A, Rahman, Anisur, Merrill, Joan T, Fortin, Paul R, Gladman, Dafna D, Bruce, Ian N, Petri, Michelle, Ginzler, Ellen M, Dooley, MA, Steinsson, Kristjan, Ramsey-Goldman, Rosalind, Zoma, Asad A, Manzi, Susan, Nived, Ola, Jonsen, Andreas, Khamashta, Munther A, Alarcón, Graciela S, van Vollenhoven, Ronald F, Aranow, Cynthia, Mackay, Meggan, Ruiz-Irastorza, Guillermo, Ramos-Casals, Manuel, Lim, S Sam, Inanc, Murat, Kalunian, Kenneth C, Jacobsen, Soren, Peschken, Christine A, Kamen, Diane L, Askanase, Anca, Theriault, Chris, and Farewell, Vernon
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Biomedical and Clinical Sciences ,Clinical Sciences ,Lupus ,Clinical Research ,Autoimmune Disease ,Mental Health ,Evaluation of treatments and therapeutic interventions ,6.1 Pharmaceuticals ,Inflammatory and immune system ,Adult ,Age Factors ,Antibodies ,Anticardiolipin ,Autoantibodies ,Cohort Studies ,Female ,Humans ,Kaplan-Meier Estimate ,Linear Models ,Lupus Coagulation Inhibitor ,Lupus Erythematosus ,Systemic ,Lupus Vasculitis ,Central Nervous System ,Male ,Middle Aged ,Proportional Hazards Models ,Prospective Studies ,Psychotic Disorders ,Receptors ,N-Methyl-D-Aspartate ,Sex Factors ,Young Adult ,beta 2-Glycoprotein I ,Immunology ,Public Health and Health Services ,Arthritis & Rheumatology ,Clinical sciences - Abstract
ObjectiveTo determine, in a large, multiethnic/multiracial, prospective inception cohort of patients with systemic lupus erythematosus (SLE), the frequency, attribution, clinical, and autoantibody associations with lupus psychosis and the short- and long-term outcomes as assessed by physicians and patients.MethodsPatients were evaluated annually for 19 neuropsychiatric (NP) events including psychosis. Scores on the Systemic Lupus Erythematosus Disease Activity Index 2000, the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index, and the Short Form 36 (SF-36) were recorded. Time to event and linear regressions were used as appropriate.ResultsOf 1,826 SLE patients, 88.8% were female and 48.8% were Caucasian. The mean ± SD age was 35.1 ± 13.3 years, the mean ± SD disease duration was 5.6 ± 4.2 months, and the mean ± SD follow-up period was 7.4 ± 4.5 years. There were 31 psychotic events in 28 of 1,826 patients (1.53%), and most patients had a single event (26 of 28 [93%]). In the majority of patients (20 of 25 [80%]) and events (28 of 31 [90%]), psychosis was attributed to SLE, usually either in the year prior to or within 3 years of SLE diagnosis. Positive associations (hazard ratios [HRs] and 95% confidence intervals [95% CIs]) with lupus psychosis were previous SLE NP events (HR 3.59 [95% CI 1.16-11.14]), male sex (HR 3.0 [95% CI 1.20-7.50]), younger age at SLE diagnosis (per 10 years) (HR 1.45 [95% CI 1.01-2.07]), and African ancestry (HR 4.59 [95% CI 1.79-11.76]). By physician assessment, most psychotic events resolved by the second annual visit following onset, in parallel with an improvement in patient-reported SF-36 summary and subscale scores.ConclusionPsychosis is an infrequent manifestation of NPSLE. Generally, it occurs early after SLE onset and has a significant negative impact on health status. As determined by patient and physician report, the short- and long-term outlooks are good for most patients, although careful follow-up is required.
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- 2019
26. Evaluating the Construct of Damage in Systemic Lupus Erythematosus
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Johnson, Sindhu R., Gladman, Dafna D., Brunner, Hermine I., Isenberg, David, Clarke, Ann E., Barber, Megan R. W., Arnaud, Laurent, Fortin, Paul R., Mosca, Marta, Voskuyl, Alexandre E., Manzi, Susan, Aranow, Cynthia, Askanase, Anca, Alarcón, Graciela S., Bae, Sang‐Cheol, Costedoat‐Chalumeau, Nathalie, English, Jessica A., Pons‐Estel, Guillermo J., Pons‐Estel, Bernardo A., Gilman, Rebecca, Ginzler, Ellen M., Hanly, John G., Jacobsen, Soren, Kalunian, Kenneth, Kamen, Diane L., Lambalgen, Chynace, Legge, Alexandra, Lim, S. Sam, Mak, Anselm, Morand, Eric F., Peschken, Christine A., Petri, Michelle, Rahman, Anisur, Ramsey‐Goldman, Rosalind, Reynolds, John A., Romero‐Diaz, Juanita, Ruiz‐Irastorza, Guillermo, Sanchez‐Guerrero, Jorge, Svenungsson, Elisabet, Touma, Zahi, Urowitz, Murray, Vinet, Evelyne, van Vollenhoven, Ronald F., Waldhauser, Heather, Wallace, Daniel J., Zoma, Asad, and Bruce, Ian N.
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- 2023
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27. Clinical Aspects of Systemic Lupus Erythematosus
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Kamen, Diane L., Zollars, Eric, and Touma, Zahi, editor
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- 2021
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28. Cerebrovascular Events in Systemic Lupus Erythematosus: Results From an International Inception Cohort Study
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Hanly, John G, Li, Qiuju, Su, Li, Urowitz, Murray B, Gordon, Caroline, Bae, Sang‐Cheol, Romero‐Diaz, Juanita, Sanchez‐Guerrero, Jorge, Bernatsky, Sasha, Clarke, Ann E, Wallace, Daniel J, Isenberg, David A, Rahman, Anisur, Merrill, Joan T, Fortin, Paul, Gladman, Dafna D, Bruce, Ian N, Petri, Michelle, Ginzler, Ellen M, Dooley, MA, Steinsson, Kristjan, Ramsey‐Goldman, Rosalind, Zoma, Asad A, Manzi, Susan, Nived, Ola, Jonsen, Andreas, Khamashta, Munther A, Alarcón, Graciela S, Chatham, Winn, Vollenhoven, Ronald F, Aranow, Cynthia, Mackay, Meggan, Ruiz‐Irastorza, Guillermo, Ramos‐Casals, Manuel, Lim, S Sam, Inanc, Murat, Kalunian, Kenneth C, Jacobsen, Soren, Peschken, Christine A, Kamen, Diane L, Askanase, Anca, Theriault, Chris, and Farewell, Vernon
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Reproductive Medicine ,Biomedical and Clinical Sciences ,Autoimmune Disease ,Clinical Research ,Lupus ,Hematology ,Stroke ,Evaluation of treatments and therapeutic interventions ,6.1 Pharmaceuticals ,Inflammatory and immune system ,Adult ,Cerebrovascular Disorders ,Female ,Humans ,Lupus Erythematosus ,Systemic ,Male ,Middle Aged ,Prospective Studies ,Quality of Life ,Young Adult ,Clinical Sciences ,Public Health and Health Services ,Psychology ,Clinical sciences ,Allied health and rehabilitation science - Abstract
ObjectiveTo determine the frequency, characteristics, and outcomes of cerebrovascular events (CerVEs), as well as clinical and autoantibody associations in a multiethnic/racial inception cohort of patients with systemic lupus erythematosus (SLE).MethodsA total of 1,826 patients were assessed annually for 19 neuropsychiatric (NP) events, including 5 types of CerVEs: 1) stroke, 2) transient ischemia, 3) chronic multifocal ischemia, 4) subarachnoid/intracranial hemorrhage, and 5) sinus thrombosis. Global disease activity (Systemic Lupus Erythematosus Disease [SLE] Activity Index 2000), damage scores (SLE International Collaborating Clinics/American College of Rheumatology Damage Index), and Short Form 36 (SF-36) scores were collected. Time to event, linear and logistic regressions, and multistate models were used as appropriate.ResultsCerVEs were the fourth most frequent NP event: 82 of 1,826 patients had 109 events; of these events, 103 were attributed to SLE, and 44 were identified at the time of enrollment. The predominant events were stroke (60 of 109 patients) and transient ischemia (28 of 109 patients). CerVEs were associated with other NP events attributed to SLE, non-SLE-attributed NP events, African ancestry (at US SLICC sites), and increased organ damage scores. Lupus anticoagulant increased the risk of first stroke and sinus thrombosis and transient ischemic attack. Physician assessment indicated resolution or improvement in the majority of patients, but patients reported sustained reduction in SF-36 summary and subscale scores following a CerVE.ConclusionCerVEs, the fourth most frequent NP event in SLE, are usually attributable to lupus. In contrast to good physician-reported outcomes, patients reported a sustained reduction in health-related quality of life following a CerVE.
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- 2018
29. Economic Evaluation of Lupus Nephritis in the Systemic Lupus International Collaborating Clinics Inception Cohort Using a Multistate Model Approach
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Barber, Megan RW, Hanly, John G, Su, Li, Urowitz, Murray B, St. Pierre, Yvan, Romero‐Diaz, Juanita, Gordon, Caroline, Bae, Sang‐Cheol, Bernatsky, Sasha, Wallace, Daniel J, Isenberg, David A, Rahman, Anisur, Ginzler, Ellen M, Petri, Michelle, Bruce, Ian N, Fortin, Paul R, Gladman, Dafna D, Sanchez‐Guerrero, Jorge, Ramsey‐Goldman, Rosalind, Khamashta, Munther A, Aranow, Cynthia, Mackay, Meggan, Alarcón, Graciela S, Manzi, Susan, Nived, Ola, Jönsen, Andreas, Zoma, Asad A, Vollenhoven, Ronald F, Ramos‐Casals, Manuel, Ruiz‐Irastorza, Guillermo, Lim, S Sam, Kalunian, Kenneth C, Inanc, Murat, Kamen, Diane L, Peschken, Christine A, Jacobsen, Soren, Askanase, Anca, Theriault, Chris, Farewell, Vernon, and Clarke, Ann E
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Reproductive Medicine ,Biomedical and Clinical Sciences ,Clinical Sciences ,Lupus ,Kidney Disease ,Autoimmune Disease ,Clinical Research ,Burden of Illness ,Renal and urogenital ,Adult ,Cohort Studies ,Female ,Health Care Costs ,Humans ,Lupus Nephritis ,Male ,Middle Aged ,Models ,Economic ,Young Adult ,Public Health and Health Services ,Psychology ,Clinical sciences ,Allied health and rehabilitation science - Abstract
ObjectiveLittle is known about the long-term costs of lupus nephritis (LN). The costs were compared between patients with and without LN using multistate modeling.MethodsPatients from 32 centers in 11 countries were enrolled in the Systemic Lupus International Collaborating Clinics inception cohort within 15 months of diagnosis and provided annual data on renal function, hospitalizations, medications, dialysis, and selected procedures. LN was diagnosed by renal biopsy or the American College of Rheumatology classification criteria. Renal function was assessed annually using the estimated glomerular filtration rate (GFR) or estimated proteinuria. A multistate model was used to predict 10-year cumulative costs by multiplying annual costs associated with each renal state by the expected state duration.ResultsA total of 1,545 patients participated; 89.3% were women, the mean ± age at diagnosis was 35.2 ± 13.4 years, 49% were white, and the mean followup duration was 6.3 ± 3.3 years. LN developed in 39.4% of these patients by the end of followup. Ten-year cumulative costs were greater in those with LN and an estimated glomerular filtration rate (GFR) 60 ml/minute) or with LN and estimated proteinuria >3 gm/day ($84,040 versus $20,499 if no LN and estimated proteinuria
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- 2018
30. Glucocorticoid use and factors associated with variability in this use in the Systemic Lupus International Collaborating Clinics Inception Cohort
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Little, Jayne, Parker, Ben, Lunt, Mark, Hanly, John G, Urowitz, Murray B, Clarke, Ann E, Romero-Diaz, Juanita, Gordon, Caroline, Bae, Sang-Cheol, Bernatsky, Sasha, Wallace, Daniel J, Merrill, Joan T, Buyon, Jill, Isenberg, David A, Rahman, Anisur, Ginzler, Ellen M, Petri, Michelle, Dooley, Mary Anne, Fortin, Paul, Gladman, Dafna D, Steinsson, Kristjan, Ramsey-Goldman, Rosalind, Khamashta, Munther A, Aranow, Cynthia, Mackay, Meggan, Alarcón, Graciela S, Manzi, Susan, Nived, Ola, Jönsen, Andreas, Zoma, Asad A, van Vollenhoven, Ronald F, Ramos-Casals, Manuel, Ruiz-Irastorza, Guillermo, Lim, Sung Sam, Kalunian, Kenneth C, Inanc, Murat, Kamen, Diane L, Peschken, Christine A, Jacobsen, Soren, Askanase, Anca, Sanchez-Guerrero, Jorge, and Bruce, Ian N
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Autoimmune Disease ,Clinical Research ,Lupus ,Inflammatory and immune system ,Good Health and Well Being ,Adult ,Algorithms ,Asia ,Cross-Sectional Studies ,Disease Progression ,Dose-Response Relationship ,Drug ,Drug Prescriptions ,Ethnicity ,Europe ,Female ,Follow-Up Studies ,Glucocorticoids ,Health Status ,Humans ,International Cooperation ,Lupus Erythematosus ,Systemic ,Male ,Morbidity ,North America ,Retrospective Studies ,Risk Factors ,Severity of Illness Index ,Time Factors ,Young Adult ,systemic lupus erythematosus ,glucocorticoids ,epidemiology ,Clinical Sciences ,Immunology ,Public Health and Health Services ,Arthritis & Rheumatology - Abstract
ObjectivesTo describe glucocorticoid (GC) use in the SLICC inception cohort and to explore factors associated with GC use. In particular we aimed to assess temporal trends in GC use and to what extent physician-related factors may influence use.MethodsPatients were recruited within 15 months of diagnosis of SLE from 33 centres between 1999 and 2011 and continue to be reviewed annually. Descriptive statistics were used to detail oral and parenteral GC use. Cross sectional and longitudinal analyses were performed to explore factors associated with GC use at enrolment and over time.ResultsWe studied 1700 patients with a mean (s.d.) follow-up duration of 7.26 (3.82) years. Over the entire study period, 1365 (81.3%) patients received oral GCs and 447 (26.3%) received parenteral GCs at some point. GC use was strongly associated with treatment centre, age, race/ethnicity, sex, disease duration and disease activity. There was no change in the proportion of patients on GCs or the average doses of GC used over time according to year of diagnosis.ConclusionGCs remain a cornerstone in SLE management and there have been no significant changes in their use over the past 10-15 years. While patient and disease factors contribute to the variation in GC use, between-centre differences suggest that physician-related factors also contribute. Evidence-based treatment algorithms are needed to inform a more standardized approach to GC use in SLE.
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- 2018
31. Anti-KIF20B autoantibodies are associated with cranial neuropathy in systemic lupus erythematosus
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Krustev, Eugene, primary, Hanly, John G, additional, Chin, Ricky, additional, Buhler, Katherine A, additional, Urowitz, Murray B, additional, Gordon, Caroline, additional, Bae, Sang-Cheol, additional, Romero-Diaz, Juanita, additional, Sánchez-Guerrero, Jorge, additional, Bernatsky, Sasha, additional, Wallace, Daniel J, additional, Isenberg, David, additional, Rahman, Anisur, additional, Merrill, Joan T, additional, Fortin, Paul R, additional, Gladman, Dafna D, additional, Bruce, Ian N, additional, Petri, Michelle A, additional, Ginzler, Ellen M, additional, Dooley, Mary Anne, additional, Ramsey-Goldman, Rosalind, additional, Manzi, Susan, additional, Jönsen, Andreas, additional, Alarcón, Graciela S, additional, van Vollenhoven, Ronald F, additional, Aranow, Cynthia, additional, Mackay, Meggan, additional, Ruiz-Irastorza, Guillermo, additional, Lim, Sam, additional, Inanc, Murat, additional, Kalunian, Kenneth C, additional, Jacobsen, Søren, additional, Peschken, Christine A, additional, Kamen, Diane L, additional, Askenase, Anca, additional, Buyon, Jill, additional, Fritzler, Marvin J, additional, Clarke, Ann E, additional, and Choi, May Y, additional
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- 2024
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32. Examining Racial Differences in Access to Primary Care for People Living with Lupus : Use of Ambulatory Care Sensitive Conditions to Measure Access
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Brown, Elizabeth A., Gebregziabher, Mulugeta, Kamen, Diane L., White, Brandi M., and Williams, Edith M.
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- 2020
33. Transancestral mapping and genetic load in systemic lupus erythematosus.
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Langefeld, Carl D, Ainsworth, Hannah C, Cunninghame Graham, Deborah S, Kelly, Jennifer A, Comeau, Mary E, Marion, Miranda C, Howard, Timothy D, Ramos, Paula S, Croker, Jennifer A, Morris, David L, Sandling, Johanna K, Almlöf, Jonas Carlsson, Acevedo-Vásquez, Eduardo M, Alarcón, Graciela S, Babini, Alejandra M, Baca, Vicente, Bengtsson, Anders A, Berbotto, Guillermo A, Bijl, Marc, Brown, Elizabeth E, Brunner, Hermine I, Cardiel, Mario H, Catoggio, Luis, Cervera, Ricard, Cucho-Venegas, Jorge M, Dahlqvist, Solbritt Rantapää, D'Alfonso, Sandra, Da Silva, Berta Martins, de la Rúa Figueroa, Iñigo, Doria, Andrea, Edberg, Jeffrey C, Endreffy, Emőke, Esquivel-Valerio, Jorge A, Fortin, Paul R, Freedman, Barry I, Frostegård, Johan, García, Mercedes A, de la Torre, Ignacio García, Gilkeson, Gary S, Gladman, Dafna D, Gunnarsson, Iva, Guthridge, Joel M, Huggins, Jennifer L, James, Judith A, Kallenberg, Cees GM, Kamen, Diane L, Karp, David R, Kaufman, Kenneth M, Kottyan, Leah C, Kovács, László, Laustrup, Helle, Lauwerys, Bernard R, Li, Quan-Zhen, Maradiaga-Ceceña, Marco A, Martín, Javier, McCune, Joseph M, McWilliams, David R, Merrill, Joan T, Miranda, Pedro, Moctezuma, José F, Nath, Swapan K, Niewold, Timothy B, Orozco, Lorena, Ortego-Centeno, Norberto, Petri, Michelle, Pineau, Christian A, Pons-Estel, Bernardo A, Pope, Janet, Raj, Prithvi, Ramsey-Goldman, Rosalind, Reveille, John D, Russell, Laurie P, Sabio, José M, Aguilar-Salinas, Carlos A, Scherbarth, Hugo R, Scorza, Raffaella, Seldin, Michael F, Sjöwall, Christopher, Svenungsson, Elisabet, Thompson, Susan D, Toloza, Sergio MA, Truedsson, Lennart, Tusié-Luna, Teresa, Vasconcelos, Carlos, Vilá, Luis M, Wallace, Daniel J, Weisman, Michael H, Wither, Joan E, Bhangale, Tushar, Oksenberg, Jorge R, Rioux, John D, Gregersen, Peter K, Syvänen, Ann-Christine, Rönnblom, Lars, Criswell, Lindsey A, Jacob, Chaim O, Sivils, Kathy L, Tsao, Betty P, Schanberg, Laura E, and Behrens, Timothy W
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Humans ,Lupus Erythematosus ,Systemic ,HLA Antigens ,Logistic Models ,Case-Control Studies ,Mutagenesis ,Insertional ,Age of Onset ,Sequence Deletion ,Genetic Load ,Multifactorial Inheritance ,Polymorphism ,Single Nucleotide ,African Continental Ancestry Group ,American Native Continental Ancestry Group ,European Continental Ancestry Group ,Hispanic Americans ,Lupus Erythematosus ,Systemic ,Mutagenesis ,Insertional ,Polymorphism ,Single Nucleotide - Abstract
Systemic lupus erythematosus (SLE) is an autoimmune disease with marked gender and ethnic disparities. We report a large transancestral association study of SLE using Immunochip genotype data from 27,574 individuals of European (EA), African (AA) and Hispanic Amerindian (HA) ancestry. We identify 58 distinct non-HLA regions in EA, 9 in AA and 16 in HA (∼50% of these regions have multiple independent associations); these include 24 novel SLE regions (P
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- 2017
34. A missense variant in NCF1 is associated with susceptibility to multiple autoimmune diseases
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Zhao, Jian, Ma, Jianyang, Deng, Yun, Kelly, Jennifer A, Kim, Kwangwoo, Bang, So-Young, Lee, Hye-Soon, Li, Quan-Zhen, Wakeland, Edward K, Qiu, Rong, Liu, Mengru, Guo, Jianping, Li, Zhanguo, Tan, Wenfeng, Rasmussen, Astrid, Lessard, Christopher J, Sivils, Kathy L, Hahn, Bevra H, Grossman, Jennifer M, Kamen, Diane L, Gilkeson, Gary S, Bae, Sang-Cheol, Gaffney, Patrick M, Shen, Nan, and Tsao, Betty P
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Biological Sciences ,Genetics ,Autoimmune Disease ,Aetiology ,2.1 Biological and endogenous factors ,Black or African American ,Asian People ,Autoimmune Diseases ,Case-Control Studies ,Female ,Genetic Predisposition to Disease ,Humans ,Lupus Erythematosus ,Systemic ,Male ,NADPH Oxidases ,Polymorphism ,Single Nucleotide ,Reactive Oxygen Species ,Sjogren's Syndrome ,White People ,Medical and Health Sciences ,Developmental Biology ,Agricultural biotechnology ,Bioinformatics and computational biology - Abstract
Systemic lupus erythematosus (SLE) is a heterogeneous autoimmune disease with a strong genetic component characterized by autoantibody production and a type I interferon signature. Here we report a missense variant (g.74779296G>A; p.Arg90His) in NCF1, encoding the p47phox subunit of the phagocyte NADPH oxidase (NOX2), as the putative underlying causal variant that drives a strong SLE-associated signal detected by the Immunochip in the GTF2IRD1-GTF2I region at 7q11.23 with a complex genomic structure. We show that the p.Arg90His substitution, which is reported to cause reduced reactive oxygen species (ROS) production, predisposes to SLE (odds ratio (OR) = 3.47 in Asians (Pmeta = 3.1 × 10-104), OR = 2.61 in European Americans, OR = 2.02 in African Americans) and other autoimmune diseases, including primary Sjögren's syndrome (OR = 2.45 in Chinese, OR = 2.35 in European Americans) and rheumatoid arthritis (OR = 1.65 in Koreans). Additionally, decreased and increased copy numbers of NCF1 predispose to and protect against SLE, respectively. Our data highlight the pathogenic role of reduced NOX2-derived ROS levels in autoimmune diseases.
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- 2017
35. Successes, challenges and lessons learned: Community-engaged research with south Carolina's Gullah population
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Spruill, Ida J, Leite, Renata Serricchio, Fernandes, Jyotika K, Kamen, Diane L, Ford, Marvella E, Jenkins, Carolyn, Hunt, Kelly J, and Andrews, Jeannette O
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- 2013
36. A Longitudinal Analysis of Outcomes of Lupus Nephritis in an International Inception Cohort Using a Multistate Model Approach
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Hanly, John G, Su, Li, Urowitz, Murray B, Romero-Diaz, Juanita, Gordon, Caroline, Bae, Sang-Cheol, Bernatsky, Sasha, Clarke, Ann E, Wallace, Daniel J, Merrill, Joan T, Isenberg, David A, Rahman, Anisur, Ginzler, Ellen M, Petri, Michelle, Bruce, Ian N, Dooley, MA, Fortin, Paul, Gladman, Dafna D, Sanchez-Guerrero, Jorge, Steinsson, Kristjan, Ramsey-Goldman, Rosalind, Khamashta, Munther A, Aranow, Cynthia, Alarcón, Graciela S, Fessler, Barri J, Manzi, Susan, Nived, Ola, Sturfelt, Gunnar K, Zoma, Asad A, van Vollenhoven, Ronald F, Ramos-Casals, Manuel, Ruiz-Irastorza, Guillermo, Lim, S Sam, Kalunian, Kenneth C, Inanc, Murat, Kamen, Diane L, Peschken, Christine A, Jacobsen, Soren, Askanase, Anca, Theriault, Chris, and Farewell, Vernon
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Biomedical and Clinical Sciences ,Clinical Sciences ,Kidney Disease ,Autoimmune Disease ,Lupus ,Clinical Research ,Adult ,Female ,Glomerular Filtration Rate ,Humans ,Internationality ,Kidney Failure ,Chronic ,Longitudinal Studies ,Lupus Nephritis ,Male ,Models ,Statistical ,Proteinuria ,Immunology ,Public Health and Health Services ,Arthritis & Rheumatology ,Clinical sciences - Abstract
ObjectiveTo study bidirectional change and predictors of change in estimated glomerular filtration rate (GFR) and proteinuria in lupus nephritis (LN) using a multistate modeling approach.MethodsPatients in the Systemic Lupus International Collaborating Clinics inception cohort were classified annually into estimated GFR state 1 (>60 ml/minute), state 2 (30-60 ml/minute), or state 3 (3.0 gm/day), or end-stage renal disease (ESRD) or death. Using multistate modeling, relative transition rates between states indicated improvement and deterioration.ResultsOf 1,826 lupus patients, 700 (38.3%) developed LN. During a mean ± SD follow-up of 5.2 ± 3.5 years, the likelihood of improvement in estimated GFR and estimated proteinuria was greater than the likelihood of deterioration. After 5 years, 62% of patients initially in estimated GFR state 3 and 11% of patients initially in estimated proteinuria state 3 transitioned to ESRD. The probability of remaining in the initial states 1, 2, and 3 was 85%, 11%, and 3%, respectively, for estimated GFR and 62%, 29%, and 4%, respectively, for estimated proteinuria. Male sex predicted improvement in estimated GFR states; older age, race/ethnicity, higher estimated proteinuria state, and higher renal biopsy chronicity scores predicted deterioration. For estimated proteinuria, race/ethnicity, earlier calendar years, damage scores without renal variables, and higher renal biopsy chronicity scores predicted deterioration; male sex, presence of lupus anticoagulant, class V nephritis, and mycophenolic acid use predicted less improvement.ConclusionIn LN, the expected improvement or deterioration in renal outcomes can be estimated by multistate modeling and is preceded by identifiable risk factors. New therapeutic interventions for LN should meet or exceed these expectations.
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- 2016
37. The frequency and outcome of lupus nephritis: results from an international inception cohort study
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Hanly, John G, O'Keeffe, Aidan G, Su, Li, Urowitz, Murray B, Romero-Diaz, Juanita, Gordon, Caroline, Bae, Sang-Cheol, Bernatsky, Sasha, Clarke, Ann E, Wallace, Daniel J, Merrill, Joan T, Isenberg, David A, Rahman, Anisur, Ginzler, Ellen M, Fortin, Paul, Gladman, Dafna D, Sanchez-Guerrero, Jorge, Petri, Michelle, Bruce, Ian N, Dooley, Mary Anne, Ramsey-Goldman, Rosalind, Aranow, Cynthia, Alarcón, Graciela S, Fessler, Barri J, Steinsson, Kristjan, Nived, Ola, Sturfelt, Gunnar K, Manzi, Susan, Khamashta, Munther A, van Vollenhoven, Ronald F, Zoma, Asad A, Ramos-Casals, Manuel, Ruiz-Irastorza, Guillermo, Lim, S Sam, Stoll, Thomas, Inanc, Murat, Kalunian, Kenneth C, Kamen, Diane L, Maddison, Peter, Peschken, Christine A, Jacobsen, Soren, Askanase, Anca, Theriault, Chris, Thompson, Kara, and Farewell, Vernon
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Biomedical and Clinical Sciences ,Clinical Sciences ,Kidney Disease ,Lupus ,Prevention ,Human Genome ,Mental Health ,Autoimmune Disease ,Genetics ,Clinical Research ,Behavioral and Social Science ,Good Health and Well Being ,Adult ,Disease Progression ,Ethnicity ,Female ,Follow-Up Studies ,Global Health ,Humans ,Incidence ,Lupus Nephritis ,Male ,Outcome Assessment ,Health Care ,Prospective Studies ,Quality of Life ,Risk Factors ,Surveys and Questionnaires ,Survival Rate ,systemic lupus erythematosus ,lupus ,nephritis ,inception cohort ,outcomes research ,Immunology ,Public Health and Health Services ,Arthritis & Rheumatology ,Clinical sciences - Abstract
ObjectiveTo determine nephritis outcomes in a prospective multi-ethnic/racial SLE inception cohort.MethodsPatients in the Systemic Lupus International Collaborating Clinics inception cohort (≤15 months of SLE diagnosis) were assessed annually for estimated glomerular filtration rate (eGFR), proteinuria and end-stage renal disease (ESRD). Health-related quality of life was measured by the Short Form (36 questions) health survey questionnaire (SF-36) subscales, mental and physical component summary scores.ResultsThere were 1827 patients, 89% females, mean (s.d.) age 35.1 (13.3) years. The mean (s.d.) SLE duration at enrolment was 0.5 (0.3) years and follow-up 4.6 (3.4) years. LN occurred in 700 (38.3%) patients: 566/700 (80.9%) at enrolment and 134/700 (19.1%) during follow-up. Patients with nephritis were younger, more frequently men and of African, Asian and Hispanic race/ethnicity. The estimated overall 10-year incidence of ESRD was 4.3% (95% CI: 2.8%, 5.8%), and with nephritis was 10.1% (95% CI: 6.6%, 13.6%). Patients with nephritis had a higher risk of death (HR = 2.98, 95% CI: 1.48, 5.99; P = 0.002) and those with eGFR
- Published
- 2016
38. Association Between Severe Nonadherence to Hydroxychloroquine and Systemic Lupus Erythematosus Flares, Damage, and Mortality in 660 Patients From the SLICC Inception Cohort
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Nguyen, Yann, primary, Blanchet, Benoît, additional, Urowitz, Murray B., additional, Hanly, John G., additional, Gordon, Caroline, additional, Bae, Sang‐Cheol, additional, Romero‐Diaz, Juanita, additional, Sanchez‐Guerrero, Jorge, additional, Clarke, Ann E., additional, Bernatsky, Sasha, additional, Wallace, Daniel J., additional, Isenberg, David A., additional, Rahman, Anisur, additional, Merrill, Joan T., additional, Fortin, Paul R., additional, Gladman, Dafna D., additional, Bruce, Ian N., additional, Petri, Michelle, additional, Ginzler, Ellen M., additional, Dooley, Mary Anne, additional, Ramsey‐Goldman, Rosalind, additional, Manzi, Susan, additional, Jönsen, Andreas, additional, Alarcón, Graciela S., additional, Van Vollenhoven, Ronald F., additional, Aranow, Cynthia, additional, Le Guern, Véronique, additional, Mackay, Meggan, additional, Ruiz‐Irastorza, Guillermo, additional, Lim, S. Sam, additional, Inanc, Murat, additional, Kalunian, Kenneth C., additional, Jacobsen, Søren, additional, Peschken, Christine A., additional, Kamen, Diane L., additional, Askanase, Anca, additional, Buyon, Jill, additional, and Costedoat‐Chalumeau, Nathalie, additional
- Published
- 2023
- Full Text
- View/download PDF
39. Genetic associations of leptin-related polymorphisms with systemic lupus erythematosus
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Zhao, Jian, Wu, Hui, Langefeld, Carl D, Kaufman, Kenneth M, Kelly, Jennifer A, Bae, Sang-Cheol, networks, Marta E Alarcón-Riquelme for the BIOLUPUS and GENLES, Alarcón, Graciela S, Anaya, Juan-Manuel, Criswell, Lindsey A, Freedman, Barry I, Kamen, Diane L, Gilkeson, Gary S, Jacob, Chaim O, James, Judith A, Merrill, Joan T, Gaffney, Patrick M, Sivils, Kathy Moser, Niewold, Timothy B, Petri, Michelle A, Song, Seung Taek, Jeong, Hye-jin, Ramsey-Goldman, Rosalind, Reveille, John D, Scofield, R Hal, Stevens, Anne M, Boackle, Susan A, Vilá, Luis M, Chang, Deh-Ming, Song, Yeong Wook, Vyse, Timothy J, Harley, John B, Brown, Elizabeth E, Edberg, Jeffrey C, Kimberly, Robert P, Hahn, Bevra H, Grossman, Jennifer M, Tsao, Betty P, and La Cava, Antonio
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Biomedical and Clinical Sciences ,Immunology ,Clinical Research ,Autoimmune Disease ,Genetic Testing ,Genetics ,Lupus ,2.1 Biological and endogenous factors ,Aetiology ,Inflammatory and immune system ,Case-Control Studies ,Genetic Predisposition to Disease ,Genotype ,Humans ,Leptin ,Lupus Erythematosus ,Systemic ,Polymorphism ,Single Nucleotide ,Systemic lupus erythematosus ,Leptin pathway ,Gene polymorphisms ,Marta E. Alarcón-Riquelme for the BIOLUPUS and GENLES networks - Abstract
Leptin is abnormally elevated in the plasma of patients with systemic lupus erythematosus (SLE), where it is thought to promote and/or sustain pro-inflammatory responses. Whether this association could reflect an increased genetic susceptibility to develop SLE is not known, and studies of genetic associations with leptin-related polymorphisms in SLE patients have been so far inconclusive. Here we genotyped DNA samples from 15,706 SLE patients and healthy matched controls from four different ancestral groups, to correlate polymorphisms of genes of the leptin pathway to risk for SLE. It was found that although several SNPs showed weak associations, those associations did not remain significant after correction for multiple testing. These data do not support associations between defined leptin-related polymorphisms and increased susceptibility to develop SLE.
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- 2015
40. Factors associated with damage accrual in patients with systemic lupus erythematosus: results from the Systemic Lupus International Collaborating Clinics (SLICC) Inception Cohort
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Bruce, Ian N, O'Keeffe, Aidan G, Farewell, Vern, Hanly, John G, Manzi, Susan, Su, Li, Gladman, Dafna D, Bae, Sang-Cheol, Sanchez-Guerrero, Jorge, Romero-Diaz, Juanita, Gordon, Caroline, Wallace, Daniel J, Clarke, Ann E, Bernatsky, Sasha, Ginzler, Ellen M, Isenberg, David A, Rahman, Anisur, Merrill, Joan T, Alarcón, Graciela S, Fessler, Barri J, Fortin, Paul R, Petri, Michelle, Steinsson, Kristjan, Dooley, Mary Anne, Khamashta, Munther A, Ramsey-Goldman, Rosalind, Zoma, Asad A, Sturfelt, Gunnar K, Nived, Ola, Aranow, Cynthia, Mackay, Meggan, Ramos-Casals, Manuel, van Vollenhoven, Ronald F, Kalunian, Kenneth C, Ruiz-Irastorza, Guillermo, Lim, Sam, Kamen, Diane L, Peschken, Christine A, Inanc, Murat, and Urowitz, Murray B
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Autoimmune Disease ,Lupus ,Clinical Research ,6.1 Pharmaceuticals ,Evaluation of treatments and therapeutic interventions ,Inflammatory and immune system ,Good Health and Well Being ,Adult ,Cohort Studies ,Disease Progression ,Ethnicity ,Female ,Health Status ,Humans ,Kaplan-Meier Estimate ,Longitudinal Studies ,Lupus Erythematosus ,Systemic ,Male ,Middle Aged ,Proportional Hazards Models ,Prospective Studies ,Quality of Life ,Young Adult ,Corticosteroids ,Inflammation ,Outcomes research ,Systemic Lupus Erythematosus ,Clinical Sciences ,Immunology ,Public Health and Health Services ,Arthritis & Rheumatology - Abstract
Background and aimsWe studied damage accrual and factors determining development and progression of damage in an international cohort of systemic lupus erythematosus (SLE) patients.MethodsThe Systemic Lupus International Collaborating Clinics (SLICC) Inception Cohort recruited patients within 15 months of developing four or more 1997 American College of Rheumatology (ACR) criteria for SLE; the SLICC/ACR damage index (SDI) was measured annually. We assessed relative rates of transition using maximum likelihood estimation in a multistate model. The Kaplan-Meier method estimated the probabilities for time to first increase in SDI score and Cox regression analysis was used to assess mortality.ResultsWe recruited 1722 patients; mean (SD) age 35.0 (13.4) years at cohort entry. Patients with damage at enrolment were more likely to have further worsening of SDI (SDI 0 vs ≥1; p
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- 2015
41. Impact of early disease factors on metabolic syndrome in systemic lupus erythematosus: data from an international inception cohort
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Parker, Ben, Urowitz, Murray B, Gladman, Dafna D, Lunt, Mark, Donn, Rachelle, Bae, Sang-Cheol, Sanchez-Guerrero, Jorge, Romero-Diaz, Juanita, Gordon, Caroline, Wallace, Daniel J, Clarke, Ann E, Bernatsky, Sasha, Ginzler, Ellen M, Isenberg, David A, Rahman, Anisur, Merrill, Joan T, Alarcón, Graciela S, Fessler, Barri J, Fortin, Paul R, Hanly, John G, Petri, Michelle, Steinsson, Kristjan, Dooley, Mary Anne, Manzi, Susan, Khamashta, Munther A, Ramsey-Goldman, Rosalind, Zoma, Asad A, Sturfelt, Gunnar K, Nived, Ola, Aranow, Cynthia, Mackay, Meggan, Ramos-Casals, Manuel, van Vollenhoven, Ronald F, Kalunian, Kenneth C, Ruiz-Irastorza, Guillermo, Lim, S Sam, Kamen, Diane L, Peschken, Christine A, Inanc, Murat, and Bruce, Ian N
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Clinical Research ,Lupus ,Autoimmune Disease ,Kidney Disease ,Prevention ,Cardiovascular ,Evaluation of treatments and therapeutic interventions ,6.1 Pharmaceuticals ,Inflammatory and immune system ,Good Health and Well Being ,Adult ,Cohort Studies ,Comorbidity ,Female ,Humans ,Logistic Models ,Lupus Erythematosus ,Systemic ,Male ,Metabolic Syndrome ,Middle Aged ,Phenotype ,Prevalence ,Young Adult ,Cardiovascular Disease ,Inflammation ,Systemic Lupus Erythematosus ,Clinical Sciences ,Immunology ,Public Health and Health Services ,Arthritis & Rheumatology - Abstract
BackgroundThe metabolic syndrome (MetS) may contribute to the increased cardiovascular risk in systemic lupus erythematosus (SLE). We examined the association between MetS and disease activity, disease phenotype and corticosteroid exposure over time in patients with SLE.MethodsRecently diagnosed (1, higher disease activity, increasing age and Hispanic or Black African race/ethnicity were independently associated with MetS over the first 2 years of follow-up in the cohort.ConclusionsMetS is a persistent phenotype in a significant proportion of patients with SLE. Renal lupus, active inflammatory disease and damage are SLE-related factors that drive MetS development while antimalarial agents appear to be protective from early in the disease course.
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- 2015
42. Randomized, Double‐Blind, Placebo‐Controlled Trial of the Effect of Vitamin D3 on the Interferon Signature in Patients With Systemic Lupus Erythematosus
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Aranow, Cynthia, Kamen, Diane L, Dall'Era, Maria, Massarotti, Elena M, Mackay, Meggan C, Koumpouras, Fotios, Coca, Andreea, Chatham, W Winn, Clowse, Megan EB, Criscione-Schreiber, Lisa G, Callahan, Sherri, Goldmuntz, Ellen A, Keyes-Elstein, Lynette, Oswald, Michaela, Gregersen, Peter K, and Diamond, Betty
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Clinical Research ,Clinical Trials and Supportive Activities ,Lupus ,Autoimmune Disease ,Nutrition ,Complementary and Integrative Health ,Evaluation of treatments and therapeutic interventions ,6.1 Pharmaceuticals ,Inflammatory and immune system ,Adaptor Proteins ,Signal Transducing ,Adult ,Antibodies ,Anti-Idiotypic ,Antigens ,Carrier Proteins ,Cholecalciferol ,Cytoskeletal Proteins ,DNA ,Dietary Supplements ,Dose-Response Relationship ,Drug ,Double-Blind Method ,Female ,Gene Expression Regulation ,Humans ,Lupus Erythematosus ,Systemic ,Male ,Microarray Analysis ,Middle Aged ,Myxovirus Resistance Proteins ,Prospective Studies ,RNA-Binding Proteins ,Vitamin D ,Clinical Sciences ,Immunology ,Public Health and Health Services ,Arthritis & Rheumatology - Abstract
ObjectiveVitamin D modulates the immune response and blocks induction of an interferon (IFN) signature by systemic lupus erythematosus (SLE) sera. This study was undertaken to investigate the effects of vitamin D supplementation on the IFN signature in patients with SLE.MethodsSLE patients (n = 57) with stable, inactive disease, a serum 25-hydroxyvitamin D (25[OH]D) level ≤20 ng/ml, an elevated anti-double-stranded DNA antibody level, and an IFN signature (as determined by measuring the expression levels of 3 IFN response genes) were randomized into a 12-week double-blind, placebo-controlled trial of vitamin D3 at doses of 2,000 IU or 4,000 IU. An IFN signature response was defined as a 50% reduction in the expression of 1 of the 3 genes or a 25% reduction in the expression of 2 of the 3 genes. Disease activity, adverse events, and endocrine effects were assessed.ResultsBaseline characteristics of the patients in the 3 treatment groups (placebo, low-dose vitamin D3 , or high-dose vitamin D3 ) were similar. Repletion of 25(OH)D (i.e., levels ≥30 ng/ml) was not observed in any of the patients who were receiving placebo, while repletion was observed in 16 of 33 patients receiving vitamin D3 . The percentage of patients with an IFN signature response did not differ among the treatment groups. Moreover, there was no difference in the percentage of patients with an IFN signature response between those who remained vitamin D deficient and those who demonstrated repletion of vitamin D. Modular microarray analysis of a subset of patients (n = 40) did not reveal changes from baseline in any modules (including the IFN-inducible module) in any of the treatment groups, and no differences in expression were found between patients who demonstrated vitamin D repletion and patients who were persistently vitamin D deficient. Vitamin D3 was well tolerated, and there were no safety concerns.ConclusionVitamin D3 supplementation up to 4,000 IU daily was safe and well-tolerated but failed to diminish the IFN signature in vitamin D-deficient SLE patients. Higher 25(OH)D levels sustained for a longer duration may be required to affect immunologic outcomes.
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- 2015
43. Lupus Risk Variant Increases pSTAT1 Binding and Decreases ETS1 Expression
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Lu, Xiaoming, Zoller, Erin E, Weirauch, Matthew T, Wu, Zhiguo, Namjou, Bahram, Williams, Adrienne H, Ziegler, Julie T, Comeau, Mary E, Marion, Miranda C, Glenn, Stuart B, Adler, Adam, Shen, Nan, Nath, Swapan K, Stevens, Anne M, Freedman, Barry I, Tsao, Betty P, Jacob, Chaim O, Kamen, Diane L, Brown, Elizabeth E, Gilkeson, Gary S, Alarcón, Graciela S, Reveille, John D, Anaya, Juan-Manuel, James, Judith A, Sivils, Kathy L, Criswell, Lindsey A, Vilá, Luis M, Alarcón-Riquelme, Marta E, Petri, Michelle, Scofield, R Hal, Kimberly, Robert P, Ramsey-Goldman, Rosalind, Bin Joo, Young, Choi, Jeongim, Bae, Sang-Cheol, Boackle, Susan A, Graham, Deborah Cunninghame, Vyse, Timothy J, Guthridge, Joel M, Gaffney, Patrick M, Langefeld, Carl D, Kelly, Jennifer A, Greis, Kenneth D, Kaufman, Kenneth M, Harley, John B, and Kottyan, Leah C
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Biological Sciences ,Biomedical and Clinical Sciences ,Genetics ,Biotechnology ,Lupus ,Autoimmune Disease ,Human Genome ,2.1 Biological and endogenous factors ,Aetiology ,Inflammatory and immune system ,Alleles ,Animals ,Asian People ,Bayes Theorem ,Genetic Predisposition to Disease ,Genotype ,Haplotypes ,Humans ,Lupus Erythematosus ,Systemic ,Mice ,Protein Binding ,Proto-Oncogene Protein c-ets-1 ,STAT1 Transcription Factor ,Medical and Health Sciences ,Genetics & Heredity ,Biological sciences ,Biomedical and clinical sciences ,Health sciences - Abstract
Genetic variants at chromosomal region 11q23.3, near the gene ETS1, have been associated with systemic lupus erythematosus (SLE), or lupus, in independent cohorts of Asian ancestry. Several recent studies have implicated ETS1 as a critical driver of immune cell function and differentiation, and mice deficient in ETS1 develop an SLE-like autoimmunity. We performed a fine-mapping study of 14,551 subjects from multi-ancestral cohorts by starting with genotyped variants and imputing to all common variants spanning ETS1. By constructing genetic models via frequentist and Bayesian association methods, we identified 16 variants that are statistically likely to be causal. We functionally assessed each of these variants on the basis of their likelihood of affecting transcription factor binding, miRNA binding, or chromatin state. Of the four variants that we experimentally examined, only rs6590330 differentially binds lysate from B cells. Using mass spectrometry, we found more binding of the transcription factor signal transducer and activator of transcription 1 (STAT1) to DNA near the risk allele of rs6590330 than near the non-risk allele. Immunoblot analysis and chromatin immunoprecipitation of pSTAT1 in B cells heterozygous for rs6590330 confirmed that the risk allele increased binding to the active form of STAT1. Analysis with expression quantitative trait loci indicated that the risk allele of rs6590330 is associated with decreased ETS1 expression in Han Chinese, but not other ancestral cohorts. We propose a model in which the risk allele of rs6590330 is associated with decreased ETS1 expression and increases SLE risk by enhancing the binding of pSTAT1.
- Published
- 2015
44. The IRF5–TNPO3 association with systemic lupus erythematosus has two components that other autoimmune disorders variably share
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Kottyan, Leah C, Zoller, Erin E, Bene, Jessica, Lu, Xiaoming, Kelly, Jennifer A, Rupert, Andrew M, Lessard, Christopher J, Vaughn, Samuel E, Marion, Miranda, Weirauch, Matthew T, Namjou, Bahram, Adler, Adam, Rasmussen, Astrid, Glenn, Stuart, Montgomery, Courtney G, Hirschfield, Gideon M, Xie, Gang, Coltescu, Catalina, Amos, Chris, Li, He, Ice, John A, Nath, Swapan K, Mariette, Xavier, Bowman, Simon, Rischmueller, Maureen, Lester, Sue, Brun, Johan G, Gøransson, Lasse G, Harboe, Erna, Omdal, Roald, Cunninghame-Graham, Deborah S, Vyse, Tim, Miceli-Richard, Corinne, Brennan, Michael T, Lessard, James A, Wahren-Herlenius, Marie, Kvarnström, Marika, Illei, Gabor G, Witte, Torsten, Jonsson, Roland, Eriksson, Per, Nordmark, Gunnel, Ng, Wan-Fai, Anaya, Juan-Manuel, Rhodus, Nelson L, Segal, Barbara M, Merrill, Joan T, James, Judith A, Guthridge, Joel M, Scofield, R Hal, Alarcon-Riquelme, Marta, Bae, Sang-Cheol, Boackle, Susan A, Criswell, Lindsey A, Gilkeson, Gary, Kamen, Diane L, Jacob, Chaim O, Kimberly, Robert, Brown, Elizabeth, Edberg, Jeffrey, Alarcón, Graciela S, Reveille, John D, Vilá, Luis M, Petri, Michelle, Ramsey-Goldman, Rosalind, Freedman, Barry I, Niewold, Timothy, Stevens, Anne M, Tsao, Betty P, Ying, Jun, Mayes, Maureen D, Gorlova, Olga Y, Wakeland, Ward, Radstake, Timothy, Martin, Ezequiel, Martin, Javier, Siminovitch, Katherine, Sivils, Kathy L Moser, Gaffney, Patrick M, Langefeld, Carl D, Harley, John B, and Kaufman, Kenneth M
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Biological Sciences ,Genetics ,Autoimmune Disease ,Biotechnology ,Lupus ,Aetiology ,2.1 Biological and endogenous factors ,Inflammatory and immune system ,Autoimmune Diseases ,Bayes Theorem ,Case-Control Studies ,Cohort Studies ,DNA-Binding Proteins ,Haplotypes ,Humans ,Interferon Regulatory Factors ,Lupus Erythematosus ,Systemic ,Male ,Polymorphism ,Single Nucleotide ,Promoter Regions ,Genetic ,beta Karyopherins ,UK Primary Sjögren's Syndrome Registry ,Medical and Health Sciences ,Genetics & Heredity - Abstract
Exploiting genotyping, DNA sequencing, imputation and trans-ancestral mapping, we used Bayesian and frequentist approaches to model the IRF5-TNPO3 locus association, now implicated in two immunotherapies and seven autoimmune diseases. Specifically, in systemic lupus erythematosus (SLE), we resolved separate associations in the IRF5 promoter (all ancestries) and with an extended European haplotype. We captured 3230 IRF5-TNPO3 high-quality, common variants across 5 ethnicities in 8395 SLE cases and 7367 controls. The genetic effect from the IRF5 promoter can be explained by any one of four variants in 5.7 kb (P-valuemeta = 6 × 10(-49); OR = 1.38-1.97). The second genetic effect spanned an 85.5-kb, 24-variant haplotype that included the genes IRF5 and TNPO3 (P-valuesEU = 10(-27)-10(-32), OR = 1.7-1.81). Many variants at the IRF5 locus with previously assigned biological function are not members of either final credible set of potential causal variants identified herein. In addition to the known biologically functional variants, we demonstrated that the risk allele of rs4728142, a variant in the promoter among the lowest frequentist probability and highest Bayesian posterior probability, was correlated with IRF5 expression and differentially binds the transcription factor ZBTB3. Our analytical strategy provides a novel framework for future studies aimed at dissecting etiological genetic effects. Finally, both SLE elements of the statistical model appear to operate in Sjögren's syndrome and systemic sclerosis whereas only the IRF5-TNPO3 gene-spanning haplotype is associated with primary biliary cirrhosis, demonstrating the nuance of similarity and difference in autoimmune disease risk mechanisms at IRF5-TNPO3.
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- 2015
45. Two Functional Lupus-Associated BLK Promoter Variants Control Cell-Type- and Developmental-Stage-Specific Transcription
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Guthridge, Joel M, Lu, Rufei, Sun, Harry, Sun, Celi, Wiley, Graham B, Dominguez, Nicolas, Macwana, Susan R, Lessard, Christopher J, Kim-Howard, Xana, Cobb, Beth L, Kaufman, Kenneth M, Kelly, Jennifer A, Langefeld, Carl D, Adler, Adam J, Harley, Isaac TW, Merrill, Joan T, Gilkeson, Gary S, Kamen, Diane L, Niewold, Timothy B, Brown, Elizabeth E, Edberg, Jeffery C, Petri, Michelle A, Ramsey-Goldman, Rosalind, Reveille, John D, Vilá, Luis M, Kimberly, Robert P, Freedman, Barry I, Stevens, Anne M, Boackle, Susan A, Criswell, Lindsey A, Vyse, Tim J, Behrens, Timothy W, Jacob, Chaim O, Alarcón-Riquelme, Marta E, Sivils, Kathy L, Choi, Jiyoung, Bin Joo, Young, Bang, So-Young, Lee, Hye-Soon, Bae, Sang-Cheol, Shen, Nan, Qian, Xiaoxia, Tsao, Betty P, Scofield, R Hal, Harley, John B, Webb, Carol F, Wakeland, Edward K, James, Judith A, Nath, Swapan K, Graham, Robert R, and Gaffney, Patrick M
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Biological Sciences ,Biomedical and Clinical Sciences ,Genetics ,Lupus ,Autoimmune Disease ,Clinical Research ,Stem Cell Research ,Aetiology ,2.1 Biological and endogenous factors ,Inflammatory and immune system ,Alleles ,Chromosomes ,Human ,Pair 8 ,Electrophoretic Mobility Shift Assay ,Female ,Genetic Predisposition to Disease ,Haplotypes ,Humans ,Lupus Erythematosus ,Systemic ,Male ,Polymorphism ,Single Nucleotide ,Promoter Regions ,Genetic ,Transcription ,Genetic ,src-Family Kinases ,Medical and Health Sciences ,Genetics & Heredity ,Biological sciences ,Biomedical and clinical sciences ,Health sciences - Abstract
Efforts to identify lupus-associated causal variants in the FAM167A/BLK locus on 8p21 are hampered by highly associated noncausal variants. In this report, we used a trans-population mapping and sequencing strategy to identify a common variant (rs922483) in the proximal BLK promoter and a tri-allelic variant (rs1382568) in the upstream alternative BLK promoter as putative causal variants for association with systemic lupus erythematosus. The risk allele (T) at rs922483 reduced proximal promoter activity and modulated alternative promoter usage. Allelic differences at rs1382568 resulted in altered promoter activity in B progenitor cell lines. Thus, our results demonstrated that both lupus-associated functional variants contribute to the autoimmune disease association by modulating transcription of BLK in B cells and thus potentially altering immune responses.
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- 2014
46. End‐Stage Renal Disease in African Americans With Lupus Nephritis Is Associated With APOL1
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Freedman, Barry I, Langefeld, Carl D, Andringa, Kelly K, Croker, Jennifer A, Williams, Adrienne H, Garner, Neva E, Birmingham, Daniel J, Hebert, Lee A, Hicks, Pamela J, Segal, Mark S, Edberg, Jeffrey C, Brown, Elizabeth E, Alarcón, Graciela S, Costenbader, Karen H, Comeau, Mary E, Criswell, Lindsey A, Harley, John B, James, Judith A, Kamen, Diane L, Lim, S Sam, Merrill, Joan T, Sivils, Kathy L, Niewold, Timothy B, Patel, Neha M, Petri, Michelle, Ramsey‐Goldman, Rosalind, Reveille, John D, Salmon, Jane E, Tsao, Betty P, Gibson, Keisha L, Byers, Joyce R, Vinnikova, Anna K, Lea, Janice P, Julian, Bruce A, Kimberly, Robert P, and Consortium, on behalf of the Lupus Nephritis–End‐Stage Renal Disease
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Biomedical and Clinical Sciences ,Clinical Sciences ,Genetics ,Kidney Disease ,Genetic Testing ,Clinical Research ,Autoimmune Disease ,Lupus ,Aetiology ,2.1 Biological and endogenous factors ,Inflammatory and immune system ,Adult ,Black or African American ,Alleles ,Apolipoprotein L1 ,Apolipoproteins ,Disease Progression ,Female ,Genetic Predisposition to Disease ,Genotype ,Humans ,Kidney Failure ,Chronic ,Lipoproteins ,HDL ,Logistic Models ,Lupus Nephritis ,Male ,Middle Aged ,Risk Factors ,White People ,Lupus Nephritis–End‐Stage Renal Disease Consortium ,Immunology ,Public Health and Health Services ,Arthritis & Rheumatology ,Clinical sciences - Abstract
ObjectiveLupus nephritis (LN) is a severe manifestation of systemic lupus erythematosus (SLE) that exhibits familial aggregation and may progress to end-stage renal disease (ESRD). LN is more prevalent among African Americans than among European Americans. This study was undertaken to investigate the hypothesis that the apolipoprotein L1 gene (APOL1) nephropathy risk alleles G1/G2, common in African Americans and rare in European Americans, contribute to the ethnic disparity in risk.MethodsAPOL1 G1 and G2 nephropathy alleles were genotyped in 855 African American SLE patients with LN-ESRD (cases) and 534 African American SLE patients without nephropathy (controls) and tested for association under a recessive genetic model, by logistic regression.ResultsNinety percent of the SLE patients were female. The mean ± SD age at SLE diagnosis was significantly lower in LN-ESRD cases than in SLE non-nephropathy controls (27.3 ± 10.9 years versus 39.5 ± 12.2 years). The mean ± SD time from SLE diagnosis to development of LN-ESRD in cases was 7.3 ± 7.2 years. The G1/G2 risk alleles were strongly associated with SLE-ESRD, with 25% of cases and 12% of controls having 2 nephropathy alleles (odds ratio [OR] 2.57, recessive model P = 1.49 × 10(-9)), and after adjustment for age, sex, and ancestry admixture (OR 2.72, P = 6.23 × 10(-6)). The age-, sex-, and admixture-adjusted population attributable risk for ESRD among patients with G1/G2 polymorphisms was 0.26, compared to 0.003 among European American patients. The mean time from SLE diagnosis to ESRD development was ∼2 years earlier among individuals with APOL1 risk genotypes (P = 0.01).ConclusionAPOL1 G1/G2 alleles strongly impact the risk of LN-ESRD in African Americans, as well as the time to progression to ESRD. The high frequency of these alleles in African Americans with near absence in European Americans explains an important proportion of the increased risk of LN-ESRD in African Americans.
- Published
- 2014
47. Mood Disorders in Systemic Lupus Erythematousus (SLE): Results from an International, Inception Cohort Study.
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Hanly, John G, Su, Li, Urowitz, Murray, Romero-Diaz, Juanita, Gordon, Caroline, Bae, Sang-Cheol, Bernatsky, Sasha R, Clarke, Ann E, Wallace, Daniel J, Merrill, Joan T, Isenberg, David A, Rahman, Anisur, Ginzler, Ellen M, Fortin, Paul, Gladman, Dafna D, Sanchez-Guerrero, Jorge, Petri, Michelle A, Bruce, Ian, Dooley, Mary Anne, Ramsey-Goldman, Rosalind, Aranow, Cynthia, Alarcon, Graciela S, Fessler, Barri J, Steinsson, Kristjan, Nived, Ola, Sturfelt, Gunnar K, Manzi, Susan, Khamashta, Munther A, van Vollenhoven, Ronald F, Zoma, Asad, Ramos-Casals, Manuel, Ruiz-Irastorza, Guillermo, Lim, S Sam, Stoll, Thomas, Inanc, Murat, Kalunian, Kenneth C, Kamen, Diane L, Maddison, Peter, Peschken, Christine A, Jacobsen, Soren, Askanase, Anca, Buyon, Jill P, Theriault, Chris, Thompson, Kara, and Farewell, Vernon
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Clinical Sciences ,Immunology ,Public Health and Health Services ,Arthritis & Rheumatology - Published
- 2014
48. Lymphoma risk in systemic lupus: effects of disease activity versus treatment.
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Bernatsky, Sasha, Ramsey-Goldman, Rosalind, Joseph, Lawrence, Boivin, Jean-Francois, Costenbader, Karen H, Urowitz, Murray B, Gladman, Dafna D, Fortin, Paul R, Nived, Ola, Petri, Michelle A, Jacobsen, Soren, Manzi, Susan, Ginzler, Ellen M, Isenberg, David, Rahman, Anisur, Gordon, Caroline, Ruiz-Irastorza, Guillermo, Yelin, Edward, Bae, Sang-Cheol, Wallace, Daniel J, Peschken, Christine A, Dooley, Mary Anne, Edworthy, Steven M, Aranow, Cynthia, Kamen, Diane L, Romero-Diaz, Juanita, Askanase, Anca, Witte, Torsten, Barr, Susan G, Criswell, Lindsey A, Sturfelt, Gunnar K, Blanco, Irene, Feldman, Candace H, Dreyer, Lene, Patel, Neha M, St Pierre, Yvan, and Clarke, Ann E
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Humans ,Hodgkin Disease ,Lymphoma ,Non-Hodgkin ,Lupus Erythematosus ,Systemic ,Mycophenolic Acid ,Cyclophosphamide ,Methotrexate ,Azathioprine ,Immunosuppressive Agents ,Glucocorticoids ,Antimalarials ,Risk Factors ,Case-Control Studies ,Adult ,Middle Aged ,Female ,Male ,Young Adult ,Disease Activity ,Epidemiology ,Systemic Lupus Erythematosus ,Treatment ,Rare Diseases ,Lupus ,Hematology ,Clinical Research ,Cancer ,Prevention ,Lymphoma ,Autoimmune Disease ,6.1 Pharmaceuticals ,Evaluation of treatments and therapeutic interventions ,Inflammatory and immune system ,Good Health and Well Being ,Clinical Sciences ,Immunology ,Public Health and Health Services ,Arthritis & Rheumatology - Abstract
ObjectiveTo examine disease activity versus treatment as lymphoma risk factors in systemic lupus erythematosus (SLE).MethodsWe performed case-cohort analyses within a multisite SLE cohort. Cancers were ascertained by regional registry linkages. Adjusted HRs for lymphoma were generated in regression models, for time-dependent exposures to immunomodulators (cyclophosphamide, azathioprine, methotrexate, mycophenolate, antimalarial drugs, glucocorticoids) demographics, calendar year, Sjogren's syndrome, SLE duration and disease activity. We used adjusted mean SLE Disease Activity Index scores (SLEDAI-2K) over time, and drugs were treated both categorically (ever/never) and as estimated cumulative doses.ResultsWe studied 75 patients with lymphoma (72 non-Hodgkin, three Hodgkin) and 4961 cancer-free controls. Most lymphomas were of B-cell origin. As is seen in the general population, lymphoma risk in SLE was higher in male than female patients and increased with age. Lymphomas occurred a mean of 12.4 years (median 10.9) after SLE diagnosis. Unadjusted and adjusted analyses failed to show a clear association of disease activity with lymphoma risk. There was a suggestion of greater exposure to cyclophosphamide and to higher cumulative steroids in lymphoma cases than the cancer-free controls.ConclusionsIn this large SLE sample, there was a suggestion of higher lymphoma risk with exposure to cyclophosphamide and high cumulative steroids. Disease activity itself was not clearly associated with lymphoma risk. Further work will focus on genetic profiles that might interact with medication exposure to influence lymphoma risk in SLE.
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- 2014
49. Prevalence of clinically meaningful antiphospholipid antibodies in patients with systemic lupus erythematosus varies by race and ethnicity
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Yelnik, Cécile M, primary, Xie, Xianhong, additional, Guerra, Marta M, additional, Costedoat-Chalumeau, Nathalie, additional, Khosroshahi, Arezou, additional, Kamen, Diane L, additional, Schwartz, Noa, additional, Katz, Patricia, additional, Minett, Margaret, additional, Amoss, R Toby, additional, Fu, April, additional, Guettrot-Imbert, Gaëlle, additional, Lazaro, Estibaliz, additional, Le Guern, Véronique, additional, Oates, Jim, additional, Dall'Era, Maria, additional, Yazdany, Jinoos, additional, Molto, Anna, additional, Kim, Mimi Y, additional, and Salmon, Jane E, additional
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- 2023
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- View/download PDF
50. Antiphospholipid Antibodies and Heart Valve Disease in Systemic Lupus Erythematosus
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Ruiz, Daniel, Oates, Jim C., and Kamen, Diane L.
- Published
- 2018
- Full Text
- View/download PDF
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