25 results on '"Sara S. McCoy"'
Search Results
2. Learn Labial Salivary Gland Biopsy Online
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Robert W. Ike and Sara S. McCoy
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Rheumatology - Published
- 2023
3. Sex hormones, body mass index, and related comorbidities associated with developing Sjögren’s disease: a nested case–control study
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Sara S. McCoy, Scott Hetzel, Jeffrey J. VanWormer, and Christie M. Bartels
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Adult ,Male ,Fibromyalgia ,Estrogens ,General Medicine ,Body Mass Index ,Sjogren's Syndrome ,Rheumatology ,Case-Control Studies ,Humans ,Osteoporosis ,Female ,Gonadal Steroid Hormones ,Retrospective Studies - Abstract
Sjögren's disease (SjD), a highly female predominant systemic autoimmune disease, peaks in perimenopause. Prior studies lack details on timing or type of sex hormone exposure. We examined SjD risk using endogenous and exogenous hormone exposure and related comorbidities.We performed a retrospective case-control study of adult women, nested within a population cohort. Cases had SjD diagnosed by a rheumatology provider or two SjD diagnoses from a non-rheumatology provider with a positive anti-SSA antibody or salivary gland biopsy. Cases were age-matched to three SjD-free controls. We calculated modified composite estrogen scores (mCES) and collected demographics, comorbidities, and endogenous and exogenous hormone exposures. Risk ratios were adjusted for demographics.Of 546 SjD cases and 1637 age-matched controls, mCES was not significantly associated with SjD in adjusted models. The top individual hormone exposures associated with SjD included estrogen replacement therapy (ERT; RR 1.78 [95% CI 1.47-2.14]), polycystic ovarian syndrome (1.65 [1.28-2.12]), and hysterectomy without bilateral oophorectomy (1.51 [1.13-2.03]). We identified comorbidities preceding SjD including fibromyalgia, pulmonary disease, diabetes, lymphoma, osteoporosis, peripheral vascular disease, and renal disease. Taking comorbidities into account, we developed a predictive model for SjD that included fibromyalgia (2.50 [1.93-3.25]), osteoporosis (1.84 [1.27-2.66]), hormone replacement therapy (HRT) (1.61 [1.22-2.12]), diabetes (0.27 [0.13-0.50]), and body mass index (BMI) (0.97 [0.95-0.99]).We report a novel algorithm to improve identifying patients at risk for SjD and describe sex hormone association with SjD. Finally, we report new comorbidities associated with SjD decrease, BMI and diabetes, and increase, lymphoma and osteoporosis.. Key Points •Given female predominance and typical perimenopausal onset, sex hormones should be considered when studying comorbidities in Sjögren's disease. •The top exposures associated with developing Sjögren's disease included fibromyalgia, osteoporosis, and use of hormone replacement therapy. Possible protective factors included prior diabetes and higher body mass index. •We used our newly identified exposures to generate a predictive algorithm, which has potential to improve diagnosis and pathogenic insights into Sjögren's disease.
- Published
- 2022
4. X-linked genes exhibit miR6891-5p-regulated skewing in Sjögren’s syndrome
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Teressa M. Shaw, Wei Zhang, Sara S. McCoy, Adam Pagenkopf, Diana M. Carp, Shivani Garg, Maxwell H. Parker, Xueer Qiu, Robert H. Scofield, Jacques Galipeau, and Yun Liang
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Drug Discovery ,Molecular Medicine ,Genetics (clinical) - Published
- 2022
5. Rheumatoid Factor and Anti–Modified Protein Antibody Reactivities Converge on IgG Epitopes
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Aisha M. Mergaert, Zihao Zheng, Michael F. Denny, Maya F. Amjadi, S. Janna Bashar, Michael A. Newton, Vivianne Malmström, Caroline Grönwall, Sara S. McCoy, and Miriam A. Shelef
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Arthritis, Rheumatoid ,Epitopes ,Sjogren's Syndrome ,Rheumatology ,Rheumatoid Factor ,Immunoglobulin G ,Immunology ,Citrulline ,Humans ,Immunology and Allergy ,Peptides ,Article ,Autoantibodies - Abstract
Rheumatoid arthritis (RA) patients often develop rheumatoid factors (RFs), antibodies that bind IgG Fc, and anti-modified protein antibodies (AMPAs), multireactive autoantibodies that commonly bind citrullinated, homocitrullinated, and acetylated antigens. Recently, antibodies that bind citrulline-containing IgG epitopes were discovered in RA, suggesting that additional undiscovered IgG epitopes could exist and that IgG could be a shared antigen for RFs and AMPAs. This study was undertaken to reveal new IgG epitopes in rheumatic disease and to determine if multireactive AMPAs bind IgG.Using sera from patients with RA, systemic lupus erythematosus, Sjögren's disease (SjD), or spondyloarthropathy, IgG binding to native, citrulline-containing, and homocitrulline-containing linear epitopes of the IgG constant region was evaluated by peptide array, with highly bound epitopes further evaluated by enzyme-linked immunosorbent assay (ELISA). Binding of monoclonal AMPAs to IgG-derived peptides and IgG Fc was also evaluated by ELISA.Seropositive RA sera showed high IgG binding to multiple citrulline- and homocitrulline-containing IgG-derived peptides, whereas anti-SSA+ sera from SjD patients showed consistent binding to a single linear native epitope of IgG in the hinge region. Monoclonal AMPAs bound citrulline- and homocitrulline-containing IgG peptides and modified IgG Fc.The repertoire of epitopes bound by AMPAs includes modified IgG epitopes, positioning IgG as a common antigen that connects the otherwise divergent reactivities of RFs and AMPAs.
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- 2022
6. Minor salivary gland mesenchymal stromal cells derived from patients with Sjӧgren's syndrome deploy intact immune plasticity
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Jayeeta Giri, Pradyut K. Paul, Yun Liang, Maxwell Parker, Sara S. McCoy, Jacques Galipeau, Rahul Das, and Andrea Pennati
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0301 basic medicine ,Cancer Research ,Immunology ,Inflammation ,Lymphocyte Activation ,Salivary Glands, Minor ,Article ,Extracellular matrix ,03 medical and health sciences ,0302 clinical medicine ,Immune system ,Fibrosis ,medicine ,Humans ,Immunology and Allergy ,Genetics (clinical) ,Cell Proliferation ,Transplantation ,Salivary gland ,business.industry ,Mesenchymal stem cell ,Mesenchymal Stem Cells ,Cell Biology ,medicine.disease ,Phenotype ,stomatognathic diseases ,030104 developmental biology ,medicine.anatomical_structure ,Oncology ,030220 oncology & carcinogenesis ,Cancer research ,Female ,medicine.symptom ,business ,Myofibroblast - Abstract
Background aims Mesenchymal stromal cells (MSCs) provide minor salivary glands (MSGs) with support and niche cells for epithelial glandular tissue. Little is known about resident MSG-derived MSCs (MSG-MSCs) in primary Sjӧgren's syndrome (PSS). The authors’ objective is to define the immunobiology of endogenous PSS MSG-MSCs. Methods Using culture-adapted MSG-MSCs isolated from consenting PSS subjects (n = 13), the authors performed in vitro interrogation of PSS MSG-MSC immunobiology and global gene expression compared with controls. To this end, the authors performed phenotypic and immune functional analysis of indoleamine 2,3-dioxygenase (IDO), programmed death ligand 1 (PD-L1) and intercellular adhesion marker 1 (ICAM-1) before and after interferon γ (IFNγ) licensing as well as the effect of MSG-MSCs on T-cell proliferation. Considering the female predominance of PSS, the authors also addressed the influence of 17-β-estradiol on estrogen receptor α-positive-related MSC function. Results The authors found that MSG-MSCs deployed normal immune regulatory functionality after IFNγ stimulation, as demonstrated by increased protein-level expression of IDO, PD-L1 and ICAM-1. The authors also found that MSG-MSCs suppressed T-cell proliferation in a dose-dependent manner independent of 17-β-estradiol exposure. Gene ontology and pathway analysis highlighted extracellular matrix deposition as a possible difference between PSS and control MSG-MSCs. MSG-MSCs demonstrated increased α-smooth muscle actin expression in PSS, indicating a partial myofibroblast-like adaptation. Conclusions These findings establish similar immune regulatory function of MSG-MSCs in both PSS and control patients, precluding intrinsic MSC immune regulatory defects in PSS. PSS MSG-MSCs show a partial imprinted myofibroblast-like phenotype that may arise in the setting of chronic inflammation, providing a plausible etiology for PSS-related glandular fibrosis.
- Published
- 2021
7. Symptom-Based Cluster Analysis Categorizes Sjögren's Disease Subtypes: An International Cohort Study Highlighting Disease Severity and Treatment Discordance
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Sara S. McCoy, Miguel Woodham, Christie M. Bartels, Ian J. Saldanha, Vatinee Y. Bunya, Noah Maerz, Esen K. Akpek, Matthew A. Makara, and Alan N. Baer
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Cohort Studies ,Sjogren's Syndrome ,Rheumatology ,Immunology ,Quality of Life ,Immunology and Allergy ,Cluster Analysis ,Humans ,Pain ,Severity of Illness Index ,Fatigue - Abstract
Although symptom relief is a critical aspect for successful drug development in Sjögren's disease, patient experiences with Sjögren's-related symptoms are understudied. Our objective was to determine how pain, dryness, and fatigue, the cardinal symptoms of Sjögren's disease, drive cluster phenotypes.We used data from the Sjögren's International Collaborative Clinical Alliance (SICCA) Registry and a Sjögren's Foundation survey. We performed hierarchical clustering of symptoms by levels of dryness, fatigue, and pain. Using international and US cohorts, we performed multiple logistic regression analysis to compare the clusters, which included comparisons of differences in symptoms, quality of life (QoL), medication use, and systemic manifestations.Four similar clusters were identified among 1,454 SICCA registrants and 2,920 Sjögren's Foundation survey participants: 1) low symptom burden in all categories (LSB); 2) dry with low pain and low fatigue (DLP); 3) dry with high pain and low to moderate fatigue (DHP); and 4) high symptom burden in all categories (HSB). Distribution of SICCA registrants matching the symptom profile for each cluster was 10% in the LSB cluster, 30% in the DLP cluster, 23% in the DHP cluster, and 37% in the HSB cluster. Distribution of survey participants matching the symptom profile for each cluster was 23% in the LSB cluster, 14% in the DLP cluster, 21% in the DHP cluster, and 42% in the HSB cluster. Individuals in the HSB cluster had more total symptoms and lower QoL but lower disease severity than those in the other clusters. Despite having milder disease as measured by laboratory tests and organ involvement, individuals in the HSB cluster received immunomodulatory treatment most often.We identified 4 symptom-based Sjögren's clusters and showed that symptom burden and immunomodulatory medication use do not correlate with Sjögren's end-organ or laboratory abnormalities. Findings highlight a discordance between objective measures and treatments and offer updates to proposed symptom-based clustering approaches.
- Published
- 2022
8. A National Survey of Burnout and Depression Among Fellows Training in Pulmonary and Critical Care Medicine
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Scott M. Lieberman, Kristin M. Burkart, Kerry L. Neall, Schartess Culpepper Pace, Apostolos Kontzias, Judith A. Furlong, Morgan I. Soffler, Rahul G. Argula, Maria Danila, Mark H. Adelman, Joseph Barney, Lynn M. Petruzzi, Matthew C. Baker, Charles D. Burger, Chadwick R. Johr, Elliot Rosenstein, Robert Vassallo, Stephen Doyle, Gregory P. Downey, Gretchen Winter, Thomas Eckmann, Jeanne Dale, Richard A. Helmers, Stanley Pillemer, Alan Baer, Tamiko Katsumoto, Keith J. Robinson, Amit Sachdev, Robert M. Kotloff, Vasileios C. Kyttaris, Rendell W. Ashton, Rachana Krishna, Sara S. McCoy, Nora Sandorfi, Kristin A. Riekert, Stamatina J. Danielides, Elizabeth R. Volkmann, Heidi Kukla, Timothy Niewold, Donald Bloch, Jennifer W. McCallister, Michelle Sharp, Jerome L. Greene, Robert I. Fox, Malik M. Khurram S. Khan, Sandra E. Zaeh, Michelle N. Eakin, Kristen L. Veraldi, Stuart S. Kassan, Peter H. Lenz, Daniel J. Wallace, Evelyn J. Bromet, Edward L. Treadwell, Robert F. Spiera, Adrian Shifren, Theresa Lawrence Ford, W. Neal Roberts, Jacqueline O’Toole, Senada Arabelovic, Matthew Koslow, Janet Lewis, Philip Cohen, Rebecca C. Keith, Thomas G. Osborn, Sarah Schafer, Justin C. Hewlett, Paul F. Dellaripa, Scott Zashin, Ruben Peredo-Wende, Chokkalingam Siva, Jay H. Ryu, Jeffrey J. Swigris, Lee Daugherty Biddison, Cynthia S. Rand, Barbara Segal, Daniel Small, Gerald W. Staton, Thomas Grader-Beck, Ghaith Noaiseh, Frederick B. Vivino, Tracy Luckhardt, James Gagermeier, Robert W. Ward, James Topilow, Kirsten Koons, and Gabriel T. Bosslet
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Pulmonary and Respiratory Medicine ,Response rate (survey) ,medicine.medical_specialty ,business.industry ,health care facilities, manpower, and services ,Public health ,education ,Graduate medical education ,MEDLINE ,Burnout ,Critical Care and Intensive Care Medicine ,Mental health ,Odds ,03 medical and health sciences ,0302 clinical medicine ,030228 respiratory system ,Medicine ,030212 general & internal medicine ,Cardiology and Cardiovascular Medicine ,business ,Intensive care medicine ,psychological phenomena and processes ,Depression (differential diagnoses) - Abstract
Background The prevalence of burnout and depressive symptoms is high among physician trainees. Research Question What is the burden of burnout and depressive symptoms among fellows training in pulmonary and critical care medicine (PCCM) and what are associated individual fellow, program, and institutional characteristics? Study Design and Methods We conducted a cross-sectional electronic survey of fellows enrolled in pulmonary, PCCM, and critical care medicine training programs in the United States to assess burnout and depressive symptoms. Burnout symptoms were measured using the Maslach Burnout Index two-item measure. The two-item Primary Care Evaluation of Mental Disorders Procedure was used to screen for depressive symptoms. For each of the two outcomes (burnout and depressive symptoms), we constructed three multivariate logistic regression models to assess individual fellow characteristics, program structure, and institutional polices associated with either burnout or depressive symptoms. Results Five hundred two of the 976 fellows who received the survey completed it—including both outcome measures—giving a response rate of 51%. Fifty percent of fellows showed positive results for either burnout or depressive symptoms, with 41% showing positive results for depressive symptoms, 32% showing positive results for burnout, and 23% showing positive results for both. Reporting a coverage system in the case of personal illness or emergency (adjusted OR [aOR], 0.44; 95% CI, 0.26-0.73) and access to mental health services (aOR, 0.14; 95% CI, 0.04-0.47) were associated with lower odds of burnout. Financial concern was associated with higher odds of depressive symptoms (aOR, 1.13; 95% CI, 1.05-1.22). Working more than 70 hours in an average clinical week and the burdens of electronic health record (EHR) documentation were associated with a higher odds of both burnout and depressive symptoms. Interpretation Given the high prevalence of burnout and depressive symptoms among fellows training in PCCM, an urgent need exists to identify solutions that address this public health crisis. Strategies such as providing an easily accessible coverage system, access to mental health resources, reducing EHR burden, addressing work hours, and addressing financial concerns among trainees may help to reduce burnout or depressive symptoms and should be studied further by the graduate medical education community.
- Published
- 2021
9. Ocular Manifestations and Burden Related to Sjögren Syndrome: Results of a Patient Survey
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Ian J. Saldanha, Alan N. Baer, Esen K. Akpek, Vatinee Y Bunya, Matthew Makara, and Sara S. McCoy
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Adult ,Male ,Pediatrics ,medicine.medical_specialty ,genetic structures ,medicine.medical_treatment ,Disease ,Sjögren syndrome ,Article ,Young Adult ,03 medical and health sciences ,0302 clinical medicine ,Cost of Illness ,Sickness Impact Profile ,medicine ,Humans ,Aged ,030304 developmental biology ,Aged, 80 and over ,0303 health sciences ,business.industry ,Odds ratio ,Middle Aged ,medicine.disease ,Dry mouth ,Health Surveys ,eye diseases ,Confidence interval ,Postal survey ,Ophthalmology ,Artificial tears ,Cross-Sectional Studies ,Sjogren's Syndrome ,Quality of Life ,030221 ophthalmology & optometry ,Dry Eye Syndromes ,Female ,Patient survey ,sense organs ,medicine.symptom ,business - Abstract
Purpose To compare the burden related to dry eye with systemic symptoms of Sjogren syndrome; to estimate the burden related to ocular treatments; and to compare the impact of dry eye and extraocular manifestations of Sjogren syndrome on various aspects of patient life. Design Cross-sectional study. Methods We conducted a postal survey of adult patients with a history of physician-diagnosed Sjogren syndrome. Results The survey was completed by 2,961 patients (mean age 65.1 years, standard deviation 11.7 years), most of whom were women (96%) and white (94%). Forty-one patients younger than 18 years of age were excluded. More than half (53%) experienced severe dry eye (ie, dry eye daily/almost daily with major impact on their life). Corresponding proportions for dry mouth and fatigue were 48% and 45%, respectively. Almost all patients (97%) had used nonprescription eye drops/artificial tears/ointments. Compared with patients who did not experience dry eye, those who experienced significant dry eye (ie, daily/almost daily dry eye) more often agreed that living with Sjogren syndrome made every day a challenge (adjusted odds ratio [OR] 3.81, 95% confidence interval [CI] 2.49 to 5.86) and added a significant emotional burden (adjusted OR 2.22, 95% CI 1.49 to 3.31). Adjusted ORs for the impact of dry eye were generally lower than those for fatigue, but were similar to dry mouth and considerably higher than use of systemic treatments for serious manifestations of the disease and diagnosis of lymphoma. Conclusions Sjogren-related dry eye is more burdensome than systemic manifestations of the disease. While fatigue has the greatest impact on patient life, the impact of dry eye is comparable to that of other systemic manifestations.
- Published
- 2020
10. National Sjögren’s Foundation Survey: Burden of Oral and Systemic Involvement on Quality of Life
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Esen K. Akpek, Ian J. Saldanha, Sara S. McCoy, Christie M. Bartels, Vatinee Y Bunya, Matthew Makara, and Alan N. Baer
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medicine.medical_specialty ,Interstitial nephritis ,Immunology ,Dental Caries ,Xerostomia ,Article ,03 medical and health sciences ,0302 clinical medicine ,Rheumatology ,Quality of life ,Internal medicine ,medicine ,Humans ,Immunology and Allergy ,030212 general & internal medicine ,Mouth ulcers ,030203 arthritis & rheumatology ,business.industry ,Interstitial lung disease ,Odds ratio ,medicine.disease ,Dry mouth ,Dysphagia ,Cryoglobulinemia ,Cross-Sectional Studies ,Sjogren's Syndrome ,Quality of Life ,medicine.symptom ,business - Abstract
Objective.To define the association between oral and systemic manifestations of Sjögren syndrome (SS) and quality of life (QOL).Methods.We analyzed a cross-sectional survey conducted by the Sjögren’s Foundation in 2016, with 2961 eligible responses. We defined oral symptom and sign exposures as parotid gland swelling, dry mouth, mouth ulcers/sores, oral candidiasis, trouble speaking, choking or dysphagia, sialolithiasis or gland infection, and dental caries. Systemic exposures included interstitial lung disease, purpura/petechiae/cryoglobulinemia, vasculitis, neuropathy, leukopenia, interstitial nephritis, renal tubular acidosis, autoimmune hepatitis, primary biliary cholangitis, or lymphoma. Outcomes included SS-specific QOL questions generated by SS experts and patients.Results.Using multivariable regression models adjusted for age, sex, race, and employment, we observed that mouth ulcers or sores, trouble speaking, and dysphagia were associated with poor quality of life. The following oral aspects had the greatest effect on the following QOL areas: (1) mouth ulcers/sores on the challenge and burden of living with SS (OR 4.26, 95% CI 2.89–6.28); (2) trouble speaking on memory and concentration (OR 4.24, 95% CI 3.28–5.48); and (3) dysphagia on functional interference (OR 4.25, 95% CI 3.13–5.79). In contrast, systemic manifestations were associated with QOL to a lesser extent or not at all.Conclusion.Oral manifestations of SS, particularly mouth ulcers or sores, trouble speaking, and dysphagia, were strongly associated with worse QOL. Further study and targeted treatment of these oral manifestations provides the opportunity to improve quality of life in patients with SS.
- Published
- 2020
11. Association of Sjögren's Syndrome With Reduced Lifetime Sex Hormone Exposure: A Case–Control Study
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Emmanuel Sampene, Sara S. McCoy, and Alan N. Baer
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030203 arthritis & rheumatology ,medicine.medical_specialty ,biology ,business.industry ,Obstetrics ,medicine.drug_class ,Case-control study ,Odds ratio ,medicine.disease ,Confidence interval ,Menopause ,03 medical and health sciences ,0302 clinical medicine ,Sex hormone-binding globulin ,Rheumatology ,Estrogen ,biology.protein ,Menarche ,Medicine ,Young adult ,business - Abstract
Objective To test whether cumulative estrogen exposure, as determined by age at menarche, age at menopause, female hormone use, hysterectomy, and parity, have an effect on the development of primary Sjogren's syndrome (SS). Methods We performed a case-control study of 2,680 women from the Sjogren's International Collaborative Clinical Alliance registry, including 1,320 registrants with primary SS and 1,360 with sicca symptoms but no key features of primary SS (sicca controls). The composite estrogen score (CES) was calculated by point assignment for early menarche (age ≤10 years), high parity (>3 pregnancies), hysterectomy, female hormone use, and late menopause (age ≥53 years). Cumulative menstrual cycling (CMC) was calculated as years menstruating minus time pregnant. Results Using a regression model that adjusted for age, recruitment site, ethnicity, education, employment status, and smoking, we observed a progressive inverse trend between primary SS and CES. The odds ratio (OR) and 95% confidence interval (95% CI) were as follows for the sicca control group: CES 1, OR 0.81 (95% CI 0.67-0.99); CES 2, OR 0.74 (95% CI 0.57-0.97); CES 3, OR 0.50 (95% CI 0.30-0.86). This trend was corroborated by analysis of CMC. At the highest level of CMC within the postmenopausal group there was a 24% reduction in cumulative sex hormone exposure among primary SS participants relative to controls. Conclusion Women with primary SS have lower estrogen exposure and CMC compared to sicca controls. Increasing estrogen exposure was negatively associated with development of primary SS. Further longitudinal studies of sex hormone exposure in primary SS are needed to confirm these findings.
- Published
- 2020
12. Anti-membrane and anti-spike antibodies are long-lasting and together discriminate between past COVID-19 infection and vaccination
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Sara S. McCoy, Gage K. Moreno, Katarina M. Braun, Maya F. Amjadi, Srishti Gupta, David H. O’Connor, Miriam A. Shelef, Aisha M Mergaert, Thomas C. Friedrich, Nasia Safdar, S. Janna Bashar, and Ryan R Adyniec
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Long lasting ,medicine.medical_specialty ,Coronavirus disease 2019 (COVID-19) ,biology ,business.industry ,Public health ,Limiting ,Herd immunity ,Vaccination ,Immunology ,biology.protein ,Medicine ,Personal health ,Antibody ,business - Abstract
The consequences of past COVID-19 infection for personal health and long-term population immunity are only starting to be revealed. Unfortunately, detecting past infection is currently a challenge, limiting clinical and research endeavors. Widely available anti-SARS-CoV-2 antibody tests cannot differentiate between past infection and vaccination given vaccine-induced anti-spike antibodies and the rapid loss of infection-induced anti-nucleocapsid antibodies. Anti-membrane antibodies develop after COVID-19, but their long-term persistence is unknown. Here, we demonstrate that anti-membrane IgG is a sensitive and specific marker of past COVID-19 infection and persists at least one year. We also confirm that anti-receptor binding domain (RBD) Ig is a long-lasting, sensitive, and specific marker of past infection and vaccination, while anti-nucleocapsid IgG lacks specificity and quickly declines after COVID-19. Thus, a combination of anti-membrane and anti-RBD antibodies can accurately differentiate between distant COVID-19 infection, vaccination, and naïve states to advance public health, individual healthcare, and research goals.
- Published
- 2021
13. Mycophenolate therapy in interstitial pneumonia with autoimmune features: a cohort study
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Emmanuel Sampene, Sara S. McCoy, Maria D. Martin, Zubin Mukadam, Scott W Aesif, Keith C. Meyer, Cristopher A. Meyer, Christie M. Bartels, Jeffrey P. Kanne, and Laurie N Rice
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medicine.medical_specialty ,Therapeutics and Clinical Risk Management ,autoimmune disease ,Mycophenolate ,Pulmonary function testing ,03 medical and health sciences ,FEV1/FVC ratio ,0302 clinical medicine ,DLCO ,Internal medicine ,Medicine ,Pharmacology (medical) ,030212 general & internal medicine ,General Pharmacology, Toxicology and Pharmaceutics ,Original Research ,mycophenolate ,interstitial lung disease ,Chemical Health and Safety ,business.industry ,Interstitial lung disease ,Retrospective cohort study ,General Medicine ,respiratory system ,medicine.disease ,3. Good health ,030228 respiratory system ,connective tissue disease ,Cohort ,business ,Safety Research ,Cohort study - Abstract
Sara S McCoy,1 Zubin Mukadam,2 Keith C Meyer,2 Jeffrey P Kanne,3 Cristopher A Meyer,3 Maria D Martin,3 Emmanuel Sampene,4 Scott W Aesif,5 Laurie N Rice,6 Christie M Bartels1 1Division of Rheumatology, Department of Internal Medicine, School of Medicine and Public Health, University of Wisconsin, Madison, WI 53705, USA; 2Division of Pulmonary and Critical Care, Department of Internal Medicine, School of Medicine and Public Health, University of Wisconsin, Madison, WI 53705, USA; 3Department of Radiology, University of Wisconsin, Madison, WI 53792-3252, USA; 4Department of Biostatistics, School of Medicine and Public Health, University of Wisconsin, Madison, WI, USA; 5Department of Pathology, University of Wisconsin, Madison, WI 53792-3252, USA; 6Department of Pulmonology, SSM Health Dean Medical Group, Madison, WI53715, USA Objectives: International experts recently characterized interstitial pneumonia with autoimmune features (IPAF) as a provisional diagnosis for patients with interstitial lung disease who have characteristics of autoimmune disease but do not meet criteria for a specific autoimmune disease. We describe clinical characteristics of IPAF patients and examine responses to mycophenolate as a therapy for IPAF.Methods: This retrospective cohort included adult patients meeting European Respiratory Society/American Thoracic Society classification criteria for IPAF. Sociodemographic, clinical, and pulmonary function test data were abstracted for patients with and without mycophenolate treatment and followed longitudinally from interstitial lung disease diagnosis for change in pulmonary function test results.Results: We identified 52 patients who met criteria for IPAF. Of 52 IPAF patients, 24 did not receive mycophenolate and 28 did, with median time to mycophenolate treatment 22 months. Changes in FVC% and percentage predicted lung diffusion capacity for carbon monoxide (DLCO%) between the mycophenolate-treated and untreated groups were not significantly different (FVC% change P=0.08, DLCO% change P=0.17). However, there was a trend toward more rapid baseline decline of both FVC% and DLCO% in the mycophenolate-treated cohort before vs after mycophenolate therapy. The slope of both FVC% and DLCO% values improved after onset of mycophenolate exposure for the treated group, although this finding was not statistically significant.Conclusion: Patients with IPAF might benefit from mycophenolate therapy. Larger prospective clinical trials are needed to evaluate the efficacy of mycophenolate for patients who meet criteria for IPAF. Keywords: interstitial lung disease, autoimmune disease, connective tissue disease, mycophenolate
- Published
- 2018
14. Sjögren’s Syndrome-Associated Lung Disease
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Sara S. McCoy and Nathan Sandbo
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030203 arthritis & rheumatology ,Pulmonary and Respiratory Medicine ,03 medical and health sciences ,medicine.medical_specialty ,0302 clinical medicine ,030228 respiratory system ,Lung disease ,business.industry ,medicine ,Sjogren s ,Critical Care and Intensive Care Medicine ,business ,Dermatology - Published
- 2017
15. Skewed escape from X-inactivation underlies female bias in Sjögren’s syndrome
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Teressa Shaw, Wei Zhang, Sara S. McCoy, Xueer Qiu, Adam Pagenkopf, Jacques Galipeau, and Yun Liang
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Immunology ,Immunology and Allergy - Abstract
Many autoimmune diseases feature strikingly increased prevalence in females, such as systemic lupus erythematosus (female-to-male ratio 9:1), systemic sclerosis (female-to-male ratio 11:1) and Sjögren’s syndrome (female-to-male ratio 14:1). However, the molecular basis underlying female-biased autoimmunity remains elusive. To address this knowledge gap, we performed transcriptomic profiling of minor salivary gland-derived mesenchymal stromal cells (MSCs) from primary Sjögren’s syndrome (pSS) patients and control subjects. While autosomal gene expression profiles were largely comparable between pSS and control MSCs, we detected major differences in the regulation of X-linked genes. In control female MSCs, X-linked genes that escaped inactivation were expressed from both parental and maternal X chromosomes with a median paternal ratio of ~0.5. However, in pSS female MSCs, escapees exhibited preferential expression from one of the two X chromosomes. Concomitantly, pSS MSCs showed decrease in XIST levels and reorganization of H3K27me3+ foci in the nucleus, suggesting a global dysregulation of X-inactivation maintenance. The skewing in X escape in pSS MSCs was accompanied by mislocation of protein products encoded by the escapees. Given the hallmark features of inflammation and fibrosis in pSS salivary glands and growing evidence supporting MSCs contributing to tissue homeostasis, our data suggests that dysregulation of X-inactivation maintenance, a female-specific process, contributes to the female-bias in pSS susceptibility.
- Published
- 2021
16. Neurological Complications of Sjögren's Syndrome: Diagnosis and Management
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Sara S. McCoy and Alan N. Baer
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030203 arthritis & rheumatology ,Autoimmune disease ,medicine.medical_specialty ,Systemic disease ,Pathology ,Neuromyelitis optica ,business.industry ,Arthritis ,General Medicine ,medicine.disease ,Dermatology ,Rheumatology ,Article ,Clinical trial ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,medicine ,Demyelinating disease ,business ,030217 neurology & neurosurgery ,Rheumatism - Abstract
Purpose of review Neurologic disease is a common extraglandular manifestation of Sjogren’s syndrome (SS), the study of which has been hampered both by the lack of uniform definitions for specific neurologic complications and by the imprecision of the tools used to diagnose SS. There is a great need to develop consensus criteria for classifying these varied neurologic manifestations, as has been done in systemic lupus erythematosus (SLE) “Arthritis and rheumatism 42:599–608, 1999”. SS patients with certain forms of neurologic involvement, such as small fiber neuropathy and sensory ataxic ganglionopathy, frequently lack anti-SSA and anti-SSB antibodies and other serologic abnormalities. In these patients, neurologic disease is often their presenting manifestation, triggering a search for underlying SS. Given the frequent seronegativity of such patients, their diagnosis of SS rests heavily on the interpretation of a labial gland biopsy. However, these biopsies are prone to misinterpretation “Vivino et al. J Rheumatol 29:938–44, 2002”, and “positive” ones are found in up to 15% of healthy volunteers “Radfar et al. Arthrit Rheumatu 47:520–4, 2002”. Better diagnostic tools are needed to determine if the frequent seronegative status of these SS patients may be related to a unique disease pathogenesis. Recent findings Recent advances in diagnostic techniques have served to define a likely pathogenetic basis for certain neurologic manifestations of SS. The advent of punch skin biopsies to analyze intraepidermal nerve fiber density and morphology has helped define pure sensory small fiber neuropathy as common in SS and the basis for both length- and non-length-dependent patterns of neuropathic pain. New protocols for magnetic resonance imaging (MRI) have enabled the recognition of dorsal root ganglionitis, a finding originally detected in pathologic studies. The advent of the anti-aquaporin-4 (AQP4) antibody test in 2004 has led to the appreciation that demyelinating disease in SS is often related to the presence of neuromyelitis optica spectrum disorder. The anti-AQP4 antibody is considered to be directly pathogenic in the brain, targeting the primary water channel proteins in the brain, expressed prominently on astrocytic foot processes. Summary There are no clinical trials evaluating the efficacy of systemic immunosuppressive therapy for peripheral or central nervous system involvement. With the recent increase in clinical trials of biologic agents for SS, which utilize systemic disease manifestations as standardized outcome measures, there is an urgency to develop appropriate definitions of neurologic complications of SS and clear parameters for clinical improvement.
- Published
- 2019
17. Targeting the inflammasome in rheumatic diseases
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Sara S. McCoy, Jasmine Stannard, and J. Michelle Kahlenberg
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Inflammasomes ,Article ,Proinflammatory cytokine ,03 medical and health sciences ,AIM2 ,Drug Delivery Systems ,0302 clinical medicine ,Rheumatic Diseases ,Physiology (medical) ,Animals ,Humans ,Medicine ,Inflammation ,030203 arthritis & rheumatology ,Toll-like receptor ,business.industry ,Biochemistry (medical) ,Public Health, Environmental and Occupational Health ,NOD-like receptor ,Interleukin ,Cryopyrin-associated periodic syndrome ,Inflammasome ,General Medicine ,medicine.disease ,Neonatal onset multisystem inflammatory disease ,Immunology ,Cytokines ,business ,Signal Transduction ,030215 immunology ,medicine.drug - Abstract
Activation of the inflammasome, a protein complex responsible for many cellular functions, including the activation of the proinflammatory cytokines interleukin (IL)-1β and IL-18, has been identified as a key participant in many rheumatic diseases including autoimmune, inflammatory, and autoinflammatory syndromes. This review will discuss the recent advances in understanding the role of this complex in various rheumatic diseases. Furthermore, it will focus on available therapies, which directly and indirectly target the inflammasome and its downstream cytokines to quiet inflammation and possibly dampen autoimmune processes.
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- 2016
18. Digital ischaemia secondary to adalimumab-induced antiphospholipid syndrome
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Shashank Cheemalavagu, Jason S. Knight, and Sara S. McCoy
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medicine.medical_specialty ,Necrosis ,medicine.drug_class ,Ischemia ,Gastroenterology ,03 medical and health sciences ,0302 clinical medicine ,Antiphospholipid syndrome ,Internal medicine ,medicine ,Adalimumab ,cardiovascular diseases ,skin and connective tissue diseases ,030203 arthritis & rheumatology ,Aspirin ,Unexpected Outcome (Positive or Negative) Including Adverse Drug Reactions ,business.industry ,Warfarin ,General Medicine ,Vitamin K antagonist ,medicine.disease ,Thrombosis ,medicine.symptom ,business ,030217 neurology & neurosurgery ,medicine.drug - Abstract
A 50-year-old woman with a history of Crohn’s disease treated with adalimumab presented with left hand pain and duskiness. Angiogram showed non-filling of the radial and digital arteries of the hand. Antiphospholipid antibody testing was positive, leading to a diagnosis of antitumour necrosis factor-induced antiphospholipid syndrome. Adalimumab was discontinued, and she was treated with the vitamin K antagonist warfarin and low-dose aspirin. Upon resolution of the antiphospholipid antibodies, she was transitioned to aspirin alone without recurrence of thrombosis.
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- 2020
19. Scleroderma keratinocytes promote fibroblast activation independent of transforming growth factor beta
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Pei-Suen Tsou, J. Michelle Kahlenberg, Celine C. Berthier, Johann E. Gudjonsson, Dinesh Khanna, Jianhua Liu, Sara S. McCoy, and Tamra J. Reed
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0301 basic medicine ,Keratinocytes ,Male ,medicine.medical_treatment ,Scleroderma, Localized ,0302 clinical medicine ,Fibrosis ,Transforming Growth Factor beta ,Pharmacology (medical) ,Chemokine CCL5 ,Cells, Cultured ,Skin ,integumentary system ,biology ,NF-kappa B ,Cell Differentiation ,Clinical Science ,Middle Aged ,Immunohistochemistry ,Up-Regulation ,medicine.anatomical_structure ,Cytokine ,Female ,Keratinocyte ,Adult ,Down-Regulation ,Real-Time Polymerase Chain Reaction ,Collagen Type I ,03 medical and health sciences ,Rheumatology ,Downregulation and upregulation ,medicine ,Humans ,RNA, Messenger ,Fibroblast ,Aged ,030203 arthritis & rheumatology ,Scleroderma, Systemic ,business.industry ,Fibroblast growth factor receptor 2 ,Gene Expression Profiling ,Transforming growth factor beta ,Fibroblast growth factor receptor 3 ,Fibroblasts ,medicine.disease ,Actins ,Collagen Type I, alpha 1 Chain ,PPAR gamma ,030104 developmental biology ,Culture Media, Conditioned ,Scleroderma, Diffuse ,biology.protein ,Cancer research ,business - Abstract
Objectives SSc is a devastating disease that results in fibrosis of the skin and other organs. Fibroblasts are a key driver of the fibrotic process through deposition of extracellular matrix. The mechanisms by which fibroblasts are induced to become pro-fibrotic remain unclear. Thus, we examined the ability of SSc keratinocytes to promote fibroblast activation and the source of this effect. Methods Keratinocytes were isolated from skin biopsies of 9 lcSSc, 10 dcSSc and 13 control patients. Conditioned media was saved from the cultures. Normal fresh primary fibroblasts were exposed to healthy control and SSc keratinocyte conditioned media in the presence or absence of neutralizing antibodies for TGF-β. Gene expression was assessed by microarrays and real-time PCR. Immunocytochemistry was performed for α-smooth muscle actin (α-SMA), collagen type 1 (COL1A1) and CCL5 expression. Results SSc keratinocyte conditioned media promoted fibroblast activation, characterized by increased α-SMA and COL1A1 mRNA and protein expression. This effect was independent of TGF-β. Microarray analysis identified upregulation of nuclear factor κB (NF-κB) and downregulation of peroxisome proliferator-activated receptor γ (PPAR-γ) pathways in both SSc subtypes. Scleroderma keratinocytes exhibited increased expression of NF-κB-regulated cytokines and chemokines and lesional skin staining confirmed upregulation of CCL5 in basal keratinocytes. Conclusion Scleroderma keratinocytes promote the activation of fibroblasts in a TGF-β-independent manner and demonstrate an imbalance in NF-κB1 and PPAR-γ expression leading to increased cytokine and CCL5 production. Further study of keratinocyte mediators of fibrosis, including CCL5, may provide novel targets for skin fibrosis therapy.
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- 2017
20. Pulmonary manifestations in late versus early systemic lupus erythematosus: A systematic review and meta-analysis
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Sara S. McCoy, Christie M. Bartels, Jennifer L. Medlin, and Karen E. Hansen
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medicine.medical_specialty ,Future studies ,Pulmonary disease ,CINAHL ,Cochrane Library ,Article ,03 medical and health sciences ,0302 clinical medicine ,Rheumatology ,Internal medicine ,Medicine ,Humans ,Lupus Erythematosus, Systemic ,030212 general & internal medicine ,Age of Onset ,skin and connective tissue diseases ,Pleurisy ,030203 arthritis & rheumatology ,Serositis ,business.industry ,Interstitial lung disease ,medicine.disease ,Anesthesiology and Pain Medicine ,Meta-analysis ,Disease Progression ,business ,Lung Diseases, Interstitial - Abstract
OBJECTIVES: Phenotypes differ between late and early-onset systemic lupus erythematosus (SLE). Prior studies suggested that there may be more pulmonary disease among late-onset patients. Our objective was to perform a systematic review and meta-analysis to evaluate the differences in pulmonary manifestations in late- versus early-onset SLE. METHODS: We searched the literature using PubMed, CINAHL, Web of Science, Cochrane Library, and EMBASE. We excluded studies that did not include American College of Rheumatology SLE classification criteria, an early-onset SLE comparison group, or those that defined late-onset SLE as
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- 2017
21. Hypothyroidism as a Risk Factor for Development of Cardiovascular Disease in Patients with Rheumatoid Arthritis
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Sara S. McCoy, Sherine E. Gabriel, Cynthia S. Crowson, and Eric L. Matteson
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Adult ,Male ,medicine.medical_specialty ,Immunology ,Arthritis, Rheumatoid ,Cohort Studies ,Hypothyroidism ,Rheumatology ,Risk Factors ,Internal medicine ,Prevalence ,medicine ,Humans ,Immunology and Allergy ,Cumulative incidence ,Longitudinal Studies ,Risk factor ,Aged ,Retrospective Studies ,business.industry ,Incidence ,Thyroid disease ,Incidence (epidemiology) ,Hazard ratio ,Retrospective cohort study ,Middle Aged ,medicine.disease ,Endocrinology ,Cardiovascular Diseases ,Cohort ,Female ,business ,Cohort study - Abstract
Objective.To determine the frequency of hypothyroidism in patients with rheumatoid arthritis (RA), and to elucidate the association of hypothyroidism and development of cardiovascular disease (CVD) in these patients.Methods.A retrospective medical record review was performed using all incident cases of adult-onset RA from Olmsted County, MN, USA, that fulfilled criteria for RA in the years 1988–2007. Patients with and without thyroid disease were followed longitudinally for the development of CVD.Results.A cohort of 650 patients with RA and an age and sex-matched comparison cohort of 650 patients without RA was assembled (both cohorts mean age 55.8 yrs; 69% were women). There was no significant difference between cohorts in the presence of hypothyroid disease or subclinical hypothyroidism at time of RA diagnosis. No significant difference was found in the cumulative incidence of hypothyroid disease between the 2 cohorts. Hypothyroid disease was found to be significantly associated with CVD in patients with RA (hazard ratio 2.0; 95% CI 1.1, 3.6). This difference remained significant and unchanged after adjustment for traditional CV risk factors (HR 2.0; 95% CI 1.1, 3.6).Conclusion.No significant difference was found in either incidence or prevalence of hypothyroidism between patients with and those without RA. Hypothyroid disease was significantly associated with CVD in patients with RA, even after adjustment for other traditional CV risk factors.
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- 2012
22. Longterm outcomes and treatment after myocardial infarction in patients with rheumatoid arthritis
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Sara S. McCoy, Cynthia S. Crowson, Eric L. Matteson, Terry M. Therneau, Véronique L. Roger, Hilal Maradit-Kremers, and Sherine E. Gabriel
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Male ,medicine.medical_specialty ,Cardiotonic Agents ,Minnesota ,Immunology ,Population ,Myocardial Infarction ,Myocardial Reperfusion ,Comorbidity ,Article ,Arthritis, Rheumatoid ,Cohort Studies ,Reperfusion therapy ,Percutaneous Coronary Intervention ,Rheumatology ,Recurrence ,Internal medicine ,medicine ,Immunology and Allergy ,Humans ,Myocardial infarction ,Risk factor ,education ,Aged ,Heart Failure ,education.field_of_study ,business.industry ,Hazard ratio ,medicine.disease ,Combined Modality Therapy ,Surgery ,Survival Rate ,Treatment Outcome ,Rheumatoid arthritis ,Cohort ,Female ,business - Abstract
Objective.To investigate the risk profiles, treatment, and outcomes of patients with rheumatoid arthritis (RA) with myocardial infarction (MI) and matched MI patients without RA.Methods.We used a population-based cohort of Olmsted County, Minnesota, residents with MI from the period 1979–2009. We identified 77 patients who fulfilled the American College of Rheumatology 1987 criteria for RA and 154 MI patients without RA matched for age, sex, and calendar year. Data collection from medical records included RA and MI characteristics, antirheumatic and cardioprotective medications, reperfusion therapy, and outcomes (mortality, heart failure, and recurrent ischemia).Results.The mean age at MI was 72.4 years and 55% of patients were female in both cohorts. Cardiovascular risk factor profiles, MI characteristics, and treatment with reperfusion therapy or cardioprotective medications were similar in MI patients with and those without RA. Patients with RA experienced poorer longterm outcomes compared to patients without RA — for mortality: hazard ratio (HR) 1.47; 95% CI 1.04, 2.08; and for recurrent ischemia: HR 1.51; 95% CI 1.04, 2.18.Conclusion.MI patients with RA received similar treatment with reperfusion therapy and cardioprotective medications and had similar short-term outcomes compared to patients without RA. Patients with RA had poorer longterm outcomes. Despite similar treatment, MI patients with RA had worse longterm outcomes than MI patients without RA.
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- 2013
23. Anti-synthetase syndrome presenting as cryptogenic organizing pneumonia
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Sara S. McCoy, Eric L. Matteson, Melissa A. Wells, Patricio Escalante, Eric M. Nelsen, and Qusay Haydour
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Pulmonary and Respiratory Medicine ,medicine.medical_specialty ,Pathology ,Case Report ,Interstitial lung disease ,Delayed diagnosis ,Internal medicine ,Anti-Jo-1 antibodies ,Biopsy ,medicine ,Polymyositis-dermatomyositis ,Lung ,medicine.diagnostic_test ,business.industry ,fungi ,food and beverages ,respiratory system ,medicine.disease ,respiratory tract diseases ,Polymyositis-Dermatomyositis ,medicine.anatomical_structure ,Atypical pneumonia ,Anti-synthetase syndrome ,business ,Cryptogenic organizing pneumonia ,Cryptogenic Organizing Pneumonia - Abstract
Interstitial lung disease (ILD) is a unique group of lung diseases that can be associated with inflammatory conditions, such as polymyositis-dermatomyositis (PM-DM). Presentation of PM-DM with ILD is not uncommon but clinical and radiological features can be similar to other conditions (e.g. atypical pneumonia) and can be challenging to diagnose. Delayed diagnosis of PM-DM can be associated with progression of pulmonary involvement and potentially increase morbidity. We report a patient presenting with pulmonary symptoms who had positive anti-Jo-1 antibodies and cryptogenic organizing pneumonia features on biopsy, which is a rare reported finding.
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24. Epidemiology of Sjögren syndrome.
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Beydon M, McCoy S, Nguyen Y, Sumida T, Mariette X, and Seror R
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- Humans, Sjogren's Syndrome, Connective Tissue Diseases epidemiology, Lupus Erythematosus, Systemic complications, Lupus Erythematosus, Systemic epidemiology, Lupus Erythematosus, Systemic diagnosis, Arthritis, Rheumatoid diagnosis, Autoimmune Diseases, Scleroderma, Systemic epidemiology
- Abstract
Sjögren syndrome is a phenotypically varied autoimmune disorder that can occur alone in primary Sjögren syndrome or in association with other connective tissue diseases (CTDs), including rheumatoid arthritis, systemic lupus erythematosus (SLE) and systemic sclerosis (SSc). The estimation of the prevalence and incidence of Sjögren syndrome varies depending on diagnostic criteria and study design, making it difficult to estimate geographical and temporal trends. Nonetheless, disease phenotype is influenced by geographical origin, which is a risk factor for systemic activity. Whether mortality in primary Sjögren syndrome is increased compared with that of the general population is not yet known, but extra-glandular manifestations, in particular lymphomas, are clear risk factors for mortality. In CTDs associated with Sjögren syndrome, lymphoma risk seems higher than that of patients with CTD alone, and there is potentially lower disease activity in SLE with Sjögren syndrome and in SSc with Sjögren syndrome than in SLE or SSc alone., (© 2023. Springer Nature Limited.)
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- 2024
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25. A STAT5-Smad3 dyad regulates adipogenic plasticity of visceral adipose mesenchymal stromal cells during chronic inflammation.
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Das R, Giri J, K Paul P, Froelich N, Chinnadurai R, McCoy S, Bushman W, and Galipeau J
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Adipogenic differentiation of visceral adipose tissue-resident multipotent mesenchymal stromal cells (VA-MSC) into adipocytes is metabolically protective. Under chronic inflammatory stress, this neoadipogenesis process is suppressed by various pro-inflammatory cytokines and growth factors. However, the underlying mechanism(s) regulating VA-MSC plasticity remains largely unexplored. Using an adipogenic differentiation screen, we identified IFNγ and TGFβ as key inhibitors of primary human VA-MSC differentiation. Further studies using human and mouse VA-MSCs and a chronic high-fat diet-fed murine model revealed that IFNγ/JAK2-activated STAT5 transcription factor is a central regulator of VA-MSC differentiation under chronic inflammatory conditions. Furthermore, our results indicate that under such conditions, IFNγ-activated STAT5 and TGFβ-activated Smad3 physically interact via Smad4. This STAT5-Smad4-Smad3 complex plays a crucial role in preventing the early adipogenic commitment of VA-MSCs by suppressing key pro-adipogenic transcription factors, including CEBPδ, CEBPα, and PPARγ. Genetic or pharmacological disruption of IFNγ-TGFβ synergy by inhibiting either STAT5 or Smad3 rescued adipogenesis under chronic inflammatory stress. Overall, our study delineates a central mechanism of MSC plasticity regulation by the convergence of multiple inflammatory signaling pathways., (© 2022. The Author(s).)
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- 2022
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