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1. Author Correction: Genome-wide association study identifies Sjögren’s risk loci with functional implications in immune and glandular cells

Author

Khatri, Bhuwan, Tessneer, Kandice L., Rasmussen, Astrid, Aghakhanian, Farhang, Reksten, Tove Ragna, Adler, Adam, Alevizos, Ilias, Anaya, Juan-Manuel, Aqrawi, Lara A., Baecklund, Eva, Brun, Johan G., Bucher, Sara Magnusson, Eloranta, Maija-Leena, Engelke, Fiona, Forsblad-d’Elia, Helena, Glenn, Stuart B., Hammenfors, Daniel, Imgenberg-Kreuz, Juliana, Jensen, Janicke Liaaen, Johnsen, Svein Joar Auglænd, Jonsson, Malin V., Kvarnström, Marika, Kelly, Jennifer A., Li, He, Mandl, Thomas, Martín, Javier, Nocturne, Gaétane, Norheim, Katrine Brække, Palm, Øyvind, Skarstein, Kathrine, Stolarczyk, Anna M., Taylor, Kimberly E., Teruel, Maria, Theander, Elke, Venuturupalli, Swamy, Wallace, Daniel J., Grundahl, Kiely M., Hefner, Kimberly S., Radfar, Lida, Lewis, David M., Stone, Donald U., Kaufman, C. Erick, Brennan, Michael T., Guthridge, Joel M., James, Judith A., Scofield, R. Hal, Gaffney, Patrick M., Criswell, Lindsey A., Jonsson, Roland, Eriksson, Per, Bowman, Simon J., Omdal, Roald, Rönnblom, Lars, Warner, Blake, Rischmueller, Maureen, Witte, Torsten, Farris, A. Darise, Mariette, Xavier, Alarcon-Riquelme, Marta E., Shiboski, Caroline H., Wahren-Herlenius, Marie, Ng, Wan-Fai, Sivils, Kathy L., Adrianto, Indra, Nordmark, Gunnel, and Lessard, Christopher J.

Published
2023
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2. Author Correction: Genome-wide association study identifies Sjögren’s risk loci with functional implications in immune and glandular cells

Author

Khatri, Bhuwan, Tessneer, Kandice L., Rasmussen, Astrid, Aghakhanian, Farhang, Reksten, Tove Ragna, Adler, Adam, Alevizos, Ilias, Anaya, Juan-Manuel, Aqrawi, Lara A., Baecklund, Eva, Brun, Johan G., Bucher, Sara Magnusson, Eloranta, Maija-Leena, Engelke, Fiona, Forsblad-d’Elia, Helena, Glenn, Stuart B., Hammenfors, Daniel, Imgenberg-Kreuz, Juliana, Jensen, Janicke Liaaen, Johnsen, Svein Joar Auglænd, Jonsson, Malin V., Kvarnström, Marika, Kelly, Jennifer A., Li, He, Mandl, Thomas, Martín, Javier, Nocturne, Gaétane, Norheim, Katrine Brække, Palm, Øyvind, Skarstein, Kathrine, Stolarczyk, Anna M., Taylor, Kimberly E., Teruel, Maria, Theander, Elke, Venuturupalli, Swamy, Wallace, Daniel J., Grundahl, Kiely M., Hefner, Kimberly S., Radfar, Lida, Lewis, David M., Stone, Donald U., Kaufman, C. Erick, Brennan, Michael T., Guthridge, Joel M., James, Judith A., Scofield, R. Hal, Gaffney, Patrick M., Criswell, Lindsey A., Jonsson, Roland, Eriksson, Per, Bowman, Simon J., Omdal, Roald, Rönnblom, Lars, Warner, Blake, Rischmueller, Maureen, Witte, Torsten, Farris, A. Darise, Mariette, Xavier, Alarcon-Riquelme, Marta E., Shiboski, Caroline H., Wahren-Herlenius, Marie, Ng, Wan-Fai, Sivils, Kathy L., Adrianto, Indra, Nordmark, Gunnel, and Lessard, Christopher J.

Published
2022
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3. Genome-wide association study identifies Sjögren’s risk loci with functional implications in immune and glandular cells

Author

Khatri, Bhuwan, Tessneer, Kandice L., Rasmussen, Astrid, Aghakhanian, Farhang, Reksten, Tove Ragna, Adler, Adam, Alevizos, Ilias, Anaya, Juan-Manuel, Aqrawi, Lara A., Baecklund, Eva, Brun, Johan G., Bucher, Sara Magnusson, Eloranta, Maija-Leena, Engelke, Fiona, Forsblad-d’Elia, Helena, Glenn, Stuart B., Hammenfors, Daniel, Imgenberg-Kreuz, Juliana, Jensen, Janicke Liaaen, Johnsen, Svein Joar Auglænd, Jonsson, Malin V., Kvarnström, Marika, Kelly, Jennifer A., Li, He, Mandl, Thomas, Martín, Javier, Nocturne, Gaétane, Norheim, Katrine Brække, Palm, Øyvind, Skarstein, Kathrine, Stolarczyk, Anna M., Taylor, Kimberly E., Teruel, Maria, Theander, Elke, Venuturupalli, Swamy, Wallace, Daniel J., Grundahl, Kiely M., Hefner, Kimberly S., Radfar, Lida, Lewis, David M., Stone, Donald U., Kaufman, C. Erick, Brennan, Michael T., Guthridge, Joel M., James, Judith A., Scofield, R. Hal, Gaffney, Patrick M., Criswell, Lindsey A., Jonsson, Roland, Eriksson, Per, Bowman, Simon J., Omdal, Roald, Rönnblom, Lars, Warner, Blake, Rischmueller, Maureen, Witte, Torsten, Farris, A. Darise, Mariette, Xavier, Alarcon-Riquelme, Marta E., Shiboski, Caroline H., Wahren-Herlenius, Marie, Ng, Wan-Fai, Sivils, Kathy L., Adrianto, Indra, Nordmark, Gunnel, and Lessard, Christopher J.

Published
2022
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5. Transancestral mapping and genetic load in systemic lupus erythematosus.

Author

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

Subjects
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

Published
2017

6. A missense variant in NCF1 is associated with susceptibility to multiple autoimmune diseases

Author

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

Subjects
Biological Sciences, Genetics, Autoimmune Disease, 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.

Published
2017

8. Lupus Risk Variant Increases pSTAT1 Binding and Decreases ETS1 Expression

Author

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

Subjects
Biological Sciences, Biomedical and Clinical Sciences, Genetics, Human Genome, Clinical Research, Autoimmune Disease, Health Disparities, Women's Health, Lupus, 2.1 Biological and endogenous factors, Inflammatory and immune system, Generic health relevance, 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

9. The IRF5–TNPO3 association with systemic lupus erythematosus has two components that other autoimmune disorders variably share

Author

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

Subjects
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.

Published
2015

10. Two Functional Lupus-Associated BLK Promoter Variants Control Cell-Type- and Developmental-Stage-Specific Transcription

Author

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

Subjects
Biological Sciences, Biomedical and Clinical Sciences, Genetics, Autoimmune Disease, Stem Cell Research, Women's Health, Lupus, 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.

Published
2014

11. End‐Stage Renal Disease in African Americans With Lupus Nephritis Is Associated With APOL1

Author

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

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Lupus, Women's Health, Clinical Research, Health Disparities, Kidney Disease, Genetics, Minority Health, Autoimmune Disease, 2.1 Biological and endogenous factors, 4.1 Discovery and preclinical testing of markers and technologies, 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
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

12. NCR3/NKp30 Contributes to Pathogenesis in Primary Sjögren’s Syndrome

Author

Rusakiewicz, Sylvie, Nocturne, Gaetane, Lazure, Thierry, Semeraro, Michaela, Flament, Caroline, Caillat-Zucman, Sophie, Sène, Damien, Delahaye, Nicolas, Vivier, Eric, Chaba, Kariman, Poirier-Colame, Vichnou, Nordmark, Gunnel, Eloranta, Maija-Leena, Eriksson, Per, Theander, Elke, Forsblad-d’Elia, Helena, Omdal, Roald, Wahren-Herlenius, Marie, Jonsson, Roland, Rönnblom, Lars, Nititham, Joanne, Taylor, Kimberly E, Lessard, Christopher J, Sivils, Kathy L Moser, Gottenberg, Jacques-Eric, Criswell, Lindsey A, Miceli-Richard, Corinne, Zitvogel, Laurence, and Mariette, Xavier

Subjects
Autoimmune Disease, Rare Diseases, Genetics, Clinical Research, Digestive Diseases, Aetiology, 2.1 Biological and endogenous factors, Inflammatory and immune system, Adult, Aged, Cell Line, Cells, Cultured, Female, Genotype, Humans, Interferon-gamma, Male, Middle Aged, Natural Cytotoxicity Triggering Receptor 3, Polymorphism, Genetic, Reverse Transcriptase Polymerase Chain Reaction, Sjogren's Syndrome, Biological Sciences, Medical and Health Sciences
Abstract

Primary Sjögren's syndrome (pSS) is a chronic autoimmune disease characterized by a lymphocytic exocrinopathy. However, patients often have evidence of systemic autoimmunity, and they are at markedly increased risk for the development of non- Hodgkin's lymphoma. Similar to other autoimmune disorders, a strong interferon (IFN) signature is present among subsets of pSS patients, although the precise etiology remains uncertain. NCR3/NKp30 is a natural killer (NK)-specific activating receptor regulating the cross talk between NK and dendritic cells and type II IFN secretion. We performed a case-control study of genetic polymorphisms of the NCR3/NKp30 gene and found that rs11575837 (G>A) residing in the promoter was associated with reduced gene transcription and function as well as protection to pSS. We also demonstrated that circulating levels of NCR3/NKp30 were significantly increased among pSS patients compared with controls and correlated with higher NCR3/NKp30 but not CD16-dependent IFN-γ secretion by NK cells. Excess accumulation of NK cells in minor salivary glands correlated with the severity of the exocrinopathy. B7H6, the ligand of NKp30, was expressed by salivary epithelial cells. These findings suggest that NK cells may promote an NKp30-dependent inflammatory state in salivary glands and that blockade of the B7H6/NKp30 axis could be clinically relevant in pSS.

Published
2013

13. Variants in the DDX6-CXCR5 autoimmune disease risk locus influence the regulatory network in immune cells and salivary gland

Author

Wiley, Mandi M, primary, Khatri, Bhuwan, additional, Joachims, Michelle L, additional, Tessneer, Kandice L, additional, Stolarczyk, Anna M, additional, Rasmussen, Astrid, additional, Anaya, Juan-Manuel, additional, Aqrawi, Lara A, additional, Bae, Sang-Cheol, additional, Baecklund, Eva, additional, Bjork, Albin, additional, Brun, Johan G, additional, Bucher, Sara Magnusson, additional, Dand, Nick, additional, Eloranta, Maija-Leena, additional, Engelke, Fiona, additional, Forsblad-d'Elia, Helena, additional, Fugmann, Cecilia, additional, Glenn, Stuart B, additional, Gong, Chen, additional, Gottenberg, Jacques-Eric, additional, Hammenfors, Daniel, additional, Imgenberg-Kreuz, Juliana, additional, Jensen, Janicke Liaaen, additional, Johnsen, Svein Joar Auglaend, additional, Jonsson, Malin V, additional, Kelly, Jennifer A, additional, Khanam, Sharmily, additional, Kim, Kwangwoo, additional, Kvarnstrom, Marika, additional, Mandl, Thomas, additional, Martin, Javier, additional, Morris, David L, additional, Nocturne, Gaetane, additional, Norheim, Katrine Braekke, additional, Olsson, Peter, additional, Palm, Oyvind, additional, Pers, Jacques-Olivier, additional, Rhodus, Nelson L, additional, Sjowall, Christopher, additional, Skarstein, Kathrine, additional, Taylor, Kimberly E, additional, Tombleson, Phil, additional, Thorlacius, Gudny Ella, additional, Venuturupalli, Swamy, additional, Vital, Edward M, additional, Wallace, Daniel J., additional, Grundahl, Kiely M, additional, Radfar, Lida, additional, Brennan, Michael T, additional, James, Judith A, additional, Scofield, R. Hal, additional, Gaffney, Patrick M, additional, Criswell, Lindsey A, additional, Jonsson, Roland, additional, Appel, Silke, additional, Eriksson, Per, additional, Bowman, Simon J, additional, Omdal, Roald, additional, Ronnblom, Lars, additional, Warner, Blake M., additional, Rischmueller, Maureen, additional, Witte, Torsten, additional, Farris, A. Darise, additional, Mariette, Xavier, additional, Shiboski, Caroline H, additional, Wahren-Herlenius, Marie, additional, Alarcon-Riquelme, Marta E, additional, Ng, Wan-Fai, additional, Sivils, Kathy L., additional, Guthridge, Joel M, additional, Adrianto, Indra, additional, Vyse, Timothy J, additional, Tsao, Betty P, additional, Nordmark, Gunnel, additional, and Lessard, Christopher J, additional

Published
2023
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15. Klinefelter's syndrome (47,XXY) is in excess among men with Sjögren's syndrome

Author

Harris, Valerie M., Sharma, Rohan, Cavett, Joshua, Kurien, Biji T., Liu, Ke, Koelsch, Kristi A., Rasmussen, Astrid, Radfar, Lida, Lewis, David, Stone, Donald U., Kaufman, C. Erick, Li, Shibo, Segal, Barbara, Wallace, Daniel J., Weisman, Michael H., Venuturupalli, Swamy, Kelly, Jennifer A., Alarcon-Riquelme, Marta E., Pons-Estel, Bernardo, Jonsson, Roland, Lu, Xianglan, Gottenberg, Jacques-Eric, Anaya, Juan-Manuel, Cunninghame-Graham, Deborah S., Huang, Andrew J.W., Brennan, Michael T., Hughes, Pamela, Alevizos, Ilias, Miceli-Richard, Corinne, Keystone, Edward C., Bykerk, Vivian P., Hirschfield, Gideon, Xie, Gang, Ng, Wan-Fai, Nordmark, Gunnel, Bucher, Sara Magnusson, Eriksson, Per, Omdal, Roald, Rhodus, Nelson L., Rischmueller, Maureen, Rohrer, Michael, Wahren-Herlenius, Marie, Witte, Torsten, Mariette, Xavier, Lessard, Christopher J., Harley, John B., Sivils, Kathy L., and Scofield, R. Hal

Published
2016
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18. Dysregulated long non-coding RNA in Sjögren’s disease impacts both interferon and adaptive immune responses

Author

Joachims, Michelle L, primary, Khatri, Bhuwan, additional, Li, Chuang, additional, Tessneer, Kandice L, additional, Ice, John A, additional, Stolarczyk, Anna M, additional, Means, Nicolas, additional, Grundahl, Kiely M, additional, Glenn, Stuart B, additional, Kelly, Jennifer A, additional, Lewis, David M, additional, Radfar, Lida, additional, Stone, Donald U, additional, Guthridge, Joel M, additional, James, Judith A, additional, Scofield, R Hal, additional, Wiley, Graham B, additional, Wren, Jonathan D, additional, Gaffney, Patrick M, additional, Montgomery, Courtney G, additional, Sivils, Kathy L, additional, Rasmussen, Astrid, additional, Farris, A Darise, additional, Adrianto, Indra, additional, and Lessard, Christopher J, additional

Published
2022
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19. Germline and somatic genetic variations of TNFAIP3 in lymphoma complicating primary Sjögren's syndrome

Author

Nocturne, Gaetane, Boudaoud, Saida, Miceli-Richard, Corinne, Viengchareun, Say, Lazure, Thierry, Nititham, Joanne, Taylor, Kimberly E., Ma, Averil, Busato, Florence, Melki, Judith, Lessard, Christopher J., Sivils, Kathy L., Dubost, Jean-Jacques, Hachulla, Eric, Gottenberg, Jacques Eric, Lombès, Marc, Tost, Jorg, Criswell, Lindsey A., and Mariette, Xavier

Published
2013
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21. Brief Report: Rare X Chromosome Abnormalities in Systemic Lupus Erythematosus and Sjögrenʼs Syndrome

Author

Sharma, Rohan, Harris, Valerie M., Cavett, Joshua, Kurien, Biji T., Liu, Ke, Koelsch, Kristi A., Fayaaz, Anum, Chaudhari, Kaustubh S., Radfar, Lida, Lewis, David, Stone, Donald U., Kaufman, C. Erick, Li, Shibo, Segal, Barbara, Wallace, Daniel J., Weisman, Michael H., Venuturupalli, Swamy, Kelly, Jennifer A., Pons‐Estel, Bernardo, Jonsson, Roland, Lu, Xianglan, Gottenberg, Jacques‐Eric, Anaya, Juan‐Manuel, Cunninghame‐Graham, Deborah S., Huang, Andrew J. W., Brennan, Michael T., Hughes, Pamela, Alevizos, Ilias, Miceli‐Richard, Corinne, Keystone, Edward C., Bykerk, Vivian P., Hirschfield, Gideon, Nordmark, Gunnel, Bucher, Sara Magnusson, Eriksson, Per, Omdal, Roald, Rhodus, Nelson L., Rischmueller, Maureen, Rohrer, Michael, Wahren‐Herlenius, Marie, Witte, Torsten, Alarcón‐Riquelme, Marta, Mariette, Xavier, Lessard, Christopher J., Harley, John B., Ng, Wan‐Fai, Rasmussen, Astrid, Sivils, Kathy L., and Scofield, R. Hal

Published
2017
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22. Author Correction: Genome-wide association study identifies Sjogrens risk loci with functional implications in immune and glandular cells (vol 13, 4287, 2022)

Author

Khatri, Bhuwan, Tessneer, Kandice L., Rasmussen, Astrid, Aghakhanian, Farhang, Reksten, Tove Ragna, Adler, Adam, Alevizos, Ilias, Anaya, Juan-Manuel, Aqrawi, Lara A., Baecklund, Eva, Brun, Johan G., Bucher, Sara Magnusson, Eloranta, Maija-Leena, Engelke, Fiona, Forsblad-dElia, Helena, Glenn, Stuart B., Hammenfors, Daniel, Imgenberg-Kreuz, Juliana, Jensen, Janicke Liaaen, Johnsen, Svein Joar Auglaend, Jonsson, Malin V., Kvarnstrom, Marika, Kelly, Jennifer A., Li, He, Mandl, Thomas, Martin, Javier, Nocturne, Gaetane, Norheim, Katrine Braekke, Palm, Oyvind, Skarstein, Kathrine, Stolarczyk, Anna M., Taylor, Kimberly E., Teruel, Maria, Theander, Elke, Venuturupalli, Swamy, Wallace, Daniel J., Grundahl, Kiely M., Hefner, Kimberly S., Radfar, Lida, Lewis, David M., Stone, Donald U., Kaufman, C. Erick, Brennan, Michael T., Guthridge, Joel M., James, Judith A., Scofield, R. Hal, Gaffney, Patrick M., Criswell, Lindsey A., Jonsson, Roland, Eriksson, Per, Bowman, Simon J., Omdal, Roald, Ronnblom, Lars, Warner, Blake, Rischmueller, Maureen, Witte, Torsten, Farris, A. Darise, Mariette, Xavier, Alarcon-Riquelme, Marta E., Shiboski, Caroline H., Wahren-Herlenius, Marie, Ng, Wan-Fai, Sivils, Kathy L., Adrianto, Indra, Nordmark, Gunnel, Lessard, Christopher J., Khatri, Bhuwan, Tessneer, Kandice L., Rasmussen, Astrid, Aghakhanian, Farhang, Reksten, Tove Ragna, Adler, Adam, Alevizos, Ilias, Anaya, Juan-Manuel, Aqrawi, Lara A., Baecklund, Eva, Brun, Johan G., Bucher, Sara Magnusson, Eloranta, Maija-Leena, Engelke, Fiona, Forsblad-dElia, Helena, Glenn, Stuart B., Hammenfors, Daniel, Imgenberg-Kreuz, Juliana, Jensen, Janicke Liaaen, Johnsen, Svein Joar Auglaend, Jonsson, Malin V., Kvarnstrom, Marika, Kelly, Jennifer A., Li, He, Mandl, Thomas, Martin, Javier, Nocturne, Gaetane, Norheim, Katrine Braekke, Palm, Oyvind, Skarstein, Kathrine, Stolarczyk, Anna M., Taylor, Kimberly E., Teruel, Maria, Theander, Elke, Venuturupalli, Swamy, Wallace, Daniel J., Grundahl, Kiely M., Hefner, Kimberly S., Radfar, Lida, Lewis, David M., Stone, Donald U., Kaufman, C. Erick, Brennan, Michael T., Guthridge, Joel M., James, Judith A., Scofield, R. Hal, Gaffney, Patrick M., Criswell, Lindsey A., Jonsson, Roland, Eriksson, Per, Bowman, Simon J., Omdal, Roald, Ronnblom, Lars, Warner, Blake, Rischmueller, Maureen, Witte, Torsten, Farris, A. Darise, Mariette, Xavier, Alarcon-Riquelme, Marta E., Shiboski, Caroline H., Wahren-Herlenius, Marie, Ng, Wan-Fai, Sivils, Kathy L., Adrianto, Indra, Nordmark, Gunnel, and Lessard, Christopher J.

Published
2022
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23. X Chromosome Dose and Sex Bias in Autoimmune Diseases: Increased Prevalence of 47,XXX in Systemic Lupus Erythematosus and Sjögrenʼs Syndrome

Author

Liu, Ke, Kurien, Biji T., Zimmerman, Sarah L., Kaufman, Kenneth M., Taft, Diana H., Kottyan, Leah C., Lazaro, Sara, Weaver, Carrie A., Ice, John A., Adler, Adam J., Chodosh, James, Radfar, Lida, Rasmussen, Astrid, Stone, Donald U., Lewis, David M., Li, Shibo, Koelsch, Kristi A., Igoe, Ann, Talsania, Mitali, Kumar, Jay, Maier-Moore, Jacen S., Harris, Valerie M., Gopalakrishnan, Rajaram, Jonsson, Roland, Lessard, James A., Lu, Xianglan, Gottenberg, Jacques-Eric, Anaya, Juan-Manuel, Cunninghame-Graham, Deborah S., Huang, Andrew J. W., Brennan, Michael T., Hughes, Pamela, Illei, Gabor G., Miceli-Richard, Corinne, Keystone, Edward C., Bykerk, Vivian P., Hirschfield, Gideon, Xie, Gang, Ng, Wan-Fai, Nordmark, Gunnel, Eriksson, Per, Omdal, Roald, Rhodus, Nelson L., Rischmueller, Maureen, Rohrer, Michael, Segal, Barbara M., Vyse, Timothy J., Wahren-Herlenius, Marie, Witte, Torsten, Pons-Estel, Bernardo, Alarcón-Riquelme, Marta E., Guthridge, Joel M., James, Judith A., Lessard, Christopher J., Kelly, Jennifer A., Thompson, Susan D., Gaffney, Patrick M., Montgomery, Courtney G., Edberg, Jeffrey C., Kimberly, Robert P., Alarcón, Graciela S., Langefeld, Carl L., Gilkeson, Gary S., Kamen, Diane L., Tsao, Betty P., McCune, Joseph W., Salmon, Jane E., Merrill, Joan T., Weisman, Michael H., Wallace, Daniel J., Utset, Tammy O., Bottinger, Erwin P., Amos, Christopher I., Siminovitch, Katherine A., Mariette, Xavier, Sivils, Kathy L., Harley, John B., and Scofield, Hal R.

Published
2016
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24. Identification of a Systemic Lupus Erythematosus Risk Locus Spanning ATG16L2, FCHSD2, and P2RY2 in Koreans

Author

Lessard, Christopher J., Sajuthi, Satria, Zhao, Jian, Kim, Kwangwoo, Ice, John A., Li, He, Ainsworth, Hannah, Rasmussen, Astrid, Kelly, Jennifer A., Marion, Miranda, Bang, So-Young, Joo, Young Bin, Choi, Jeongim, Lee, Hye-Soon, Kang, Young Mo, Suh, Chang-Hee, Chung, Won Tae, Lee, Soo-Kon, Choe, Jung-Yoon, Shim, Seung Cheol, Oh, Ji Hee, Kim, Young Jin, Han, Bok-Ghee, Shen, Nan, Howe, Hwee Siew, Wakeland, Edward K., Li, Quan-Zhen, Song, Yeong Wook, Gaffney, Patrick M., Alarcón-Riquelme, Marta E., Criswell, Lindsey A., Jacob, Chaim O., Kimberly, Robert P., Vyse, Timothy J., Harley, John B., Sivils, Kathy L., Bae, Sang-Cheol, Langefeld, Carl D., and Tsao, Betty P.

Published
2016
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25. Genome-Wide Association Study in an Amerindian Ancestry Population Reveals Novel Systemic Lupus Erythematosus Risk Loci and the Role of European Admixture

Author

Alarcón-Riquelme, Marta E., Ziegler, Julie T., Molineros, Julio, Howard, Timothy D., Moreno-Estrada, Andrés, Sánchez-Rodríguez, Elena, Ainsworth, Hannah C., Ortiz-Tello, Patricia, Comeau, Mary E., Rasmussen, Astrid, Kelly, Jennifer A., Adler, Adam, Acevedo-Vázquez, Eduardo M., Mariano Cucho-Venegas, Jorge, García-De la Torre, Ignacio, Cardiel, Mario H., Miranda, Pedro, Catoggio, Luis J., Maradiaga-Ceceña, Marco, Gaffney, Patrick M., Vyse, Timothy J., Criswell, Lindsey A., Tsao, Betty P., Sivils, Kathy L., Bae, Sang-Cheol, James, Judith A., Kimberly, Robert P., Kaufman, Kenneth M., Harley, John B., Esquivel-Valerio, Jorge A., Moctezuma, José F., García, Mercedes A., Berbotto, Guillermo A., Babini, Alejandra M., Scherbarth, Hugo, Toloza, Sergio, Baca, Vicente, Nath, Swapan K., Aguilar Salinas, Carlos, Orozco, Lorena, Tusié-Luna, Teresa, Zidovetzki, Raphael, Pons-Estel, Bernardo A., Langefeld, Carl D., and Jacob, Chaim O.

Published
2016
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28. Brief Report: Patients With Primary Sjögrenʼs Syndrome Who Are Positive for Autoantibodies to Tripartite Motif–Containing Protein 38 Show Greater Disease Severity

Author

Wolska, Nina, Rybakowska, Paulina, Rasmussen, Astrid, Brown, Michael, Montgomery, Courtney, Klopocki, Arkadiusz, Grundahl, Kiely, Scofield, Robert H., Radfar, Lida, Stone, Donald U., Anaya, Juan M., Ice, John A., Lessard, Christopher J., Lewis, David M., Rhodus, Nelson L., Gopalakrishnan, Rajaram, Huang, Andrew J. W., Hughes, Pamela J., Rohrer, Michael D., Weisman, Michael H., Venuturupalli, Swamy, Guthridge, Joel M., James, Judith A., Sivils, Kathy L., Bagavant, Harini, and Deshmukh, Umesh S.

Published
2016
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29. Defining disease activity states and clinically meaningful improvement in primary Sjögrenʼs syndrome with EULAR primary Sjögrenʼs syndrome disease activity (ESSDAI) and patient-reported indexes (ESSPRI)

Author

Seror, Raphaèle, Bootsma, Hendrika, Saraux, Alain, Bowman, Simon J, Theander, Elke, Brun, Johan G, Baron, Gabriel, Le Guern, Véronique, Devauchelle-Pensec, Valérie, Ramos-Casals, Manel, Valim, Valeria, Dörner, Thomas, Tzioufas, Athanasios, Gottenberg, Jacques-Eric, Solans Laqué, Roser, Mandl, Thomas, Hachulla, Eric, Sivils, Kathy L, Ng, Wan-Fai, Fauchais, Anne-Laure, Bombardieri, Stefano, Priori, Roberta, Bartoloni, Elena, Goeb, Vincent, Praprotnik, Sonja, Sumida, Takayuki, Nishiyama, Sumusu, Caporali, Roberto, Kruize, Aike A, Vollenweider, Cristina, Ravaud, Philippe, Meiners, Petra, Brito-Zerón, Pilar, Vitali, Claudio, Mariette, Xavier, Gerli, Roberto, Kallenberg, Cees, Brun, Johan G, De Vita, Salvatore, Devauchelle, Valerie, Gottenberg, Jacques Eric, Demoulins, Frederic, Montecucco, Carlomaurizio, Tomsic, Matija, Casals, Manel Ramos, Scofield, Hal, Valesini, Guido, Devauchelle, Valerie, Saraux, Alain, Dubost, Jean-Jacques, Fauchais, Anne-Laure, Sibilia, Jean, Hayem, Gilles, Hatron, Pierre- Yves, Larroche, Claire, Guern, Veronique Le, Puéchal, Xavier, Morel, Jacques, Pedriger, Aleth, Rist, Stephanie, Sene, Damien, and Vittecoq, Olivier

Published
2016
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31. Validation of EULAR primary Sjögrenʼs syndrome disease activity (ESSDAI) and patient indexes (ESSPRI)

Author

Seror, Raphaèle, Theander, Elke, Brun, Johan G, Ramos-Casals, Manel, Valim, Valeria, Dörner, Thomas, Bootsma, Hendrika, Tzioufas, Athanasios, Solans-Laqué, Roser, Mandl, Thomas, Gottenberg, Jacques-Eric, Hachulla, Eric, Sivils, Kathy L, Ng, Wan-Fai, Fauchais, Anne-Laure, Bombardieri, Stefano, Valesini, Guido, Bartoloni, Elena, Saraux, Alain, Tomsic, Matija, Sumida, Takayuki, Nishiyama, Susumu, Caporali, Roberto, Kruize, Aike A, Vollenweider, Cristina, Ravaud, Philippe, Vitali, Claudio, Mariette, Xavier, Bowman, Simon J, Gerli, Roberto, Kallenberg, Cees, Meiners, Petra, De Vita, Salvatore, Devauchelle, Valerie, Demoulins, Frederic, Montecucco, Carlomaurizio, Praprotnik, Sonja, and Scofield, Hal

Published
2015
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32. Defective Efferocytosis in a Murine Model of Sjögren’s Syndrome Is Mediated by Dysfunctional Mer Tyrosine Kinase Receptor

Author

Witas, Richard, primary, Rasmussen, Astrid, additional, Scofield, Robert H., additional, Radfar, Lida, additional, Stone, Donald U., additional, Grundahl, Kiely, additional, Lewis, David, additional, Sivils, Kathy L., additional, Lessard, Christopher J., additional, Farris, A. Darise, additional, and Nguyen, Cuong Q., additional

Published
2021
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35. Comparison of the American-European Consensus Group Sjögrenʼs syndrome classification criteria to newly proposed American College of Rheumatology criteria in a large, carefully characterised sicca cohort

Author

Rasmussen, Astrid, Ice, John A, Li, He, Grundahl, Kiely, Kelly, Jennifer A, Radfar, Lida, Stone, Donald U, Hefner, Kimberly S, Anaya, Juan-Manuel, Rohrer, Michael, Gopalakrishnan, Rajaram, Houston, Glen D, Lewis, David M, Chodosh, James, Harley, John B, Hughes, Pamela, Maier-Moore, Jacen S, Montgomery, Courtney G, Rhodus, Nelson L, Farris, A Darise, Segal, Barbara M, Jonsson, Roland, Lessard, Christopher J, Scofield, R Hal, and Sivils, Kathy L Moser

Published
2014
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37. Transcriptomic and Network Analysis of Minor Salivary Glands of Patients With Primary Sjögren’s Syndrome

Author

Oyelakin, Akinsola, primary, Horeth, Erich, additional, Song, Eun-Ah Christine, additional, Min, Sangwon, additional, Che, Monika, additional, Marzullo, Brandon, additional, Lessard, Christopher J., additional, Rasmussen, Astrid, additional, Radfar, Lida, additional, Scofield, R. Hal, additional, Lewis, David M., additional, Stone, Donald U., additional, Grundahl, Kiely, additional, De Rossi, Scott S., additional, Kurago, Zoya, additional, Farris, A. Darise, additional, Sivils, Kathy L., additional, Sinha, Satrajit, additional, Kramer, Jill M., additional, and Romano, Rose-Anne, additional

Published
2021
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38. Sjögren’s Syndrome Minor Salivary Gland CD4+ Memory T Cells Associate with Glandular Disease Features and Have a Germinal Center T Follicular Helper Transcriptional Profile

Author

Joachims, Michelle L., primary, Leehan, Kerry M., additional, Dozmorov, Mikhail G., additional, Georgescu, Constantin, additional, Pan, Zijian, additional, Lawrence, Christina, additional, Marlin, M. Caleb, additional, Macwana, Susan, additional, Rasmussen, Astrid, additional, Radfar, Lida, additional, Lewis, David M., additional, Stone, Donald U., additional, Grundahl, Kiely, additional, Scofield, R. Hal, additional, Lessard, Christopher J., additional, Wren, Jonathan D., additional, Thompson, Linda F., additional, Guthridge, Joel M., additional, Sivils, Kathy L., additional, Moore, Jacen S., additional, and Farris, A. Darise, additional

Published
2020
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39. American Indians Have a Higher Risk of Sjögren's Syndrome and More Disease Activity Than European Americans and African Americans

Author

Scofield, R. Hal, primary, Sharma, Rohan, additional, Pezant, Nathan, additional, Kelly, Jennifer A., additional, Radfar, Lida, additional, Lewis, David M., additional, Kaufman, C. Erick, additional, Cioli, Sarah, additional, Harris, Judy, additional, Grundahl, Kiely, additional, Rhodus, Nelson L., additional, Wallace, Daniel J., additional, Weisman, Michael H., additional, Venuturupalli, Swamy, additional, Brennan, Michael T., additional, Koelsch, Kristi A., additional, Lessard, Christopher J., additional, Montgomery, Courtney G., additional, Sivils, Kathy L., additional, and Rasmussen, Astrid, additional

Published
2020
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40. Sjögren’s syndrome minor salivary gland CD4+ T cells associate with glandular disease features and have a germinal center T follicular helper transcriptional profile

Author

Farris, A. Darise, primary, Joachims, Michelle L, additional, Leehan, Kerry M, additional, Dozmorov, Mikhail G, additional, Georgescu, Constantin, additional, Pan, Zijian, additional, Rasmussen, Astrid, additional, Radfar, Lida, additional, Lewis, David M, additional, Stone, Donald U, additional, Grundahl, Kiely, additional, Scofield, R. Hal, additional, Lessard, Christopher J, additional, Wren, Jonathan D, additional, Thompson, Linda F, additional, Sivils, Kathy L, additional, and Moore, Jacen S, additional

Published
2020
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42. How immunological profile drives clinical phenotype of primary Sjögren’s syndrome at diagnosis: analysis of 10.500 patients (Sjögren Big data project

Author

Retamozo, Soledad, Acar-Denizli, Nihan, Ng, Wan-Fai, Rasmussen, Astrid, Mandl, Thomas, Seror, Raphaele, Li, Xiaomei, Baldini, Chiara, Gottenberg, Jacques-Eric, Danda, Debashish, Quartuccio, Luca, Priori, Roberta, Hernandez-Molina, Gabriala, Armagan, Berkan, Kruize, Aike A, Kwok, Seung-Ki, Kvarnström, Marika, Praprotnik, Sonja, Sène, Damien, Bartoloni, Elena, Solans, Roser, Rischmueller, Maureen, Suzuki, Yasunori, Isenberg, David A, Valim, Valeria, Wiland, Piotr, Nordmark, Gunnel, Fraile, Guadalupe, Bootsma, Hendrika, Nakamura, Takashi, Giacomelli, Roberto, Devauchelle-Pensec, Valérie, Knopf, Andreas, Bombardieri, Michele, Trevisani, Virginia Fernandes, Hammenfors, Daniel S, Pasoto, Sandra G, Gheita, Tamer A, Atzeni, Fabiola, Morel, Jacques, Vollenveider, Cristina, Horvath, Ildiko-Fanny, Sivils, Kathy L, Olsson, Peter, De Vita, Salvatore, Sánchez-Guerrero, Jorge, Kilic, Levent, Wahren-Herlenius, Marie, Mariette, Xavier, Ramos-Casals, Manuel, Brito-Zerón, Pilar, INICSA, UNC, CONICED, Cordoba, Rheumatology Unit, Cordoba (Institute University of Biomedical Sciences University of Cordoba (IUCBC), Department of Statistics, Istanbul, Mimar Sinan Üniversitesi, Institute of Cellular Medicine [Newcastle], Newcastle University [Newcastle], Oklahoma Medical Research Foundation (OMRF), Department of Rheumatology, Skane University Hospital, Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), Departement of Rheumatology and Immunology, Hefei (Anhui Provincial Hospital), Rheumatology Unit (Rheum Unit - PISA), University of Pisa - Università di Pisa, Immuno-Rhumatologie Moléculaire, Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Department of Clinical Immunology and Rheumatology, Vellore (Christian Medical College & Hospital), Rheumatology Clinic, Academic Hospital S.M. Della Misericordia, Udine, Department of Internal Medicine [Rome, Italy] (DMISM), Università degli Studi di Roma 'La Sapienza' = Sapienza University [Rome], Immunology and Rheumatology Department, Mexico City, Rheumatology, Hacettepe University Faculty of Medicine, Ankara, Hacettepe University = Hacettepe Üniversitesi, University Medical Center [Utrecht], Seoul St Mary's Hospital, Seoul, Unit of Experimental Rheumatology, Stockhom (Department of Medicine), Department of Rheumatology (Dep Rheumato - Ljubljana - SLOVENIE), University Medical Centre Slovenia, Hôpital Lariboisière, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Lariboisière-Fernand-Widal [APHP], Department of Medicine [Perugia, Italy] (Rheumatology, Unit), Università degli Studi di Perugia (UNIPG), Vall d'Hebron University Hospital [Barcelona], The Queen Elizabeth Hospital, Adelaide, Human Information Processing Laboratory - Japanese Advances Institute of Science and Technology [Ishikawa] (HIP/JAIST), JAIST - Ishikawa - Japon, Centre for Rheumatology and Connective Tissue Diseases (University College London, Royal Free Hospital), Centre for Rheumatology - London, Department of Medicine, Universidade Federal do Espirito Santo, Vitoria, Department of Rheumatology and Internal Medicine, Wroclaw, Department of Medical Sciences, Uppsala (Section of Rheumatology), Department of Internal Medicine, Madrid, Department of Rheumatology and Clinical Immunology Groningen (Dep Rheum - GRONINGEN), University Medical Center Groningen [Groningen] (UMCG), Department of Radiology and Cancer Biology, Nagasaki, University of L'Aquila [Italy] (UNIVAQ), Lymphocyte B et Auto-immunité (LBAI), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO), CHRU Brest - Service de Rhumatologie (CHU - BREST - Rhumato), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Otorhinolaryngology/Head and Neck Surgery, Munich, Centre for Experimental Medicine and Rheumatology, London, Federal University of São Paulo, Department of Clinical Science and Department of Rheumatology, Bergen, Rheumatology Division, Hospital das Clinicas, Sao Paulo (HCFMUSP), Rheumatology Department, Cairo, Istituto Ortopedico Galeazzi-IRCCS, Département de Rhumatologie[Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Lapeyronie, German Hospital, Buenos Aires, Department of Immunology [Debrecen, Hungary], University of Debrecen [Hungary], Department of Rheumatology (Dep Rheumato - Malmo - SUEDE), Skåne University Hospital, Department of Medical Area, University Hospital Santa Maria della Misericordia, Udine, Ospedale 'Santa Maria della Misericordia' = University Hospital 'Santa Maria della Misericordia', Department of Immunology [Mexico City], Natl Inst Pediat, Immunodeficiencies Res Unit, Mexico City, DF, Mexico, Rheumatology, Hacetttepe University Faculty of Medicine, Ankara, Department of Medicine Solna, CHU Le Kremlin-Bicêtre (Rheumatology Department), Department of Rheumatology, University of Barcelona, CELLEX-IDIBAPS Department of Autoimmune Diseases, Barcelona, Systemic Autoimmune Disease Unit, Department of Internal Medicine, Vall d'Hebron University Hospital, Barcelona, Spain, Department of Medicine, Universitat Autonòma, Barcelona, CHU Cochin [AP-HP], Sapienza University [Rome], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Lariboisière, University Hospital 'Santa Maria della Misericordia', and Michel, Geneviève

Subjects
[SDV] Life Sciences [q-bio], [SDV]Life Sciences [q-bio], ComputingMilieux_MISCELLANEOUS
Abstract

International audience

Published
2018

43. Evidence for Alternate Modes of B cell Activation Involving Fab Acquired-N-Glycosylations in Antibody Secreting Cells Infiltrating the Labial Salivary Glands of Sjögren’s Syndrome Patients

Author

Koelsch, Kristi A., Cavett, Joshua, Smith, Kenneth, Moore, Jacen S., Lehoux, Sylvain D., Jia, Nan, Mather, Tim, Quadri, Syed M. S., Rasmussen, Astrid, Kaufman, C. Erick, Lewis, David M., Radfar, Lida, Scordino, Teresa A., Lessard, Christopher J., Kurien, Biji T., Cummings, Richard D., James, Judith A., Sivils, Kathy L., Farris, A. Darise, and Scofield, R. Hal

Subjects
Adult, Male, B-Lymphocytes, Glycosylation, Middle Aged, Lymphocyte Activation, Article, Salivary Glands, Sjogren's Syndrome, Humans, Female, Somatic Hypermutation, Immunoglobulin, Antibody-Producing Cells, Aged, Cell Proliferation
Abstract

To better understand the role of B cells, the potential mechanisms responsible for their aberrant activation, and the production of autoantibodies in the pathogenesis of Sjögren's syndrome (SS), this study explored patterns of selection pressure and sites of N-glycosylation acquired by somatic mutation (acN-glyc) in the IgG variable (V) regions of antibody-secreting cells (ASCs) isolated from the minor salivary glands of patients with SS and non-SS control patients with sicca symptoms.A novel method to produce and characterize recombinant monoclonal antibodies (mAb) from single cell-sorted ASC infiltrates was applied to concurrently probe expressed genes (all heavy- and light-chain isotypes as well as any other gene of interest not related to immunoglobulin) in the labial salivary glands of patients with SS and non-SS controls. V regions were amplified by reverse transcription-polymerase chain reaction, sequenced, and analyzed for the incidence of N-glycosylation and selection pressure. For specificity testing, the amplified regions were expressed as either the native mAb or mutant mAb lacking the acN-glyc motif. Protein modeling was used to demonstrate how even an acN-glyc site outside of the complementarity-determining region could participate in, or inhibit, antigen binding.V-region sequence analyses revealed clonal expansions and evidence of secondary light-chain editing and allelic inclusion, of which neither of the latter two have previously been reported in patients with SS. Increased frequencies of acN-glyc were found in the sequences from patients with SS, and these acN-glyc regions were associated with an increased number of replacement mutations and lowered selection pressure. A clonal set of polyreactive mAb with differential framework region 1 acN-glyc motifs was also identified, and removal of the acN-glyc could nearly abolish binding to autoantigens.These findings support the notion of an alternative mechanism for the selection and proliferation of some autoreactive B cells, involving V-region N-glycosylation, in patients with SS.

Published
2018

44. Unique Sjögren’s syndrome patient subsets defined by molecular features

Author

James, Judith A, primary, Guthridge, Joel M, primary, Chen, Hua, primary, Lu, Rufei, primary, Bourn, Rebecka L, primary, Bean, Krista, primary, Munroe, Melissa E, primary, Smith, Miles, primary, Chakravarty, Eliza, primary, Baer, Alan N, primary, Noaiseh, Ghaith, primary, Parke, Ann, primary, Boyle, Karen, primary, Keyes-Elstein, Lynette, primary, Coca, Andreea, primary, Utset, Tammy, primary, Genovese, Mark C, primary, Pascual, Virginia, primary, Utz, Paul J, primary, Holers, V. Michael, primary, Deane, Kevin D, primary, Sivils, Kathy L, primary, Aberle, Teresa, primary, Wallace, Daniel J, primary, McNamara, James, primary, Franchimont, Nathalie, primary, and St. Clair, E. William, primary

Published
2019
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45. Reproducibility of Ocular Surface Staining in the Assessment of Sjögren Syndrome–Related Keratoconjunctivitis Sicca: Implications on Disease Classification

Author

Rasmussen, Astrid, primary, Stone, Donald U., additional, Kaufman, C. Erick, additional, Hefner, Kimberly S., additional, Fram, Nicole R., additional, Siatkowski, Rhea L., additional, Huang, Andrew J. W., additional, Chodosh, James, additional, Rasmussen, Pablo T., additional, Fife, Dustin A., additional, Pezant, Nathan, additional, Grundahl, Kiely, additional, Radfar, Lida, additional, Lewis, David M., additional, Weisman, Michael H., additional, Venuturupalli, Swamy, additional, Wallace, Daniel J., additional, Rhodus, Nelson L., additional, Brennan, Michael T., additional, Montgomery, Courtney G., additional, Lessard, Christopher J., additional, Scofield, R. Hal, additional, and Sivils, Kathy L., additional

Published
2019
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47. Epidemiologic subsets drive a differentiated clinical and immunological presentation of primary Sjögren syndrome: analysis of 9302 patients from the big data International Sjögren Cohort

Author

Retamozo, Soledad, Brito-Zeron, Pilar, Zeher, Margit, Sivils Kathy, L, Seror, Raphaele, Mandl, Thomas, Li, Xiaomei, Baldini, Chiara, Gottenberg, Jacques-Eric, Danda, Debashish, Priori, Roberta, Quartuccio, Luca, Hernandez-Molina, Gabriela, Kruize Aike, A., Kwok, Seung-Ki, Wahren-Herlenius, Marie, Sene, Damien, Gerli, Roberto, Solans, Roser, Suzuki, yasunori, Isenberg David, A., Rischmueller, Maureen, Nordmark, Gunnel, Fraile, Guadalupe, Wiland, Piotr, Bootsma, Hendrika, Nakamura, Takashi, Valim, Valeria, Giacomelli, Roberto, Devauchelle-Pensec, Valérie, Hofauer, Benedikt, Bombardieri, Michèle, Fernandes Moça Trevisani, Virginia, Hammenfors, Daniel S., Carsons Steven, E., Pasoto, Gofinet, Morel, Jacques, Gheita, Tamer, Atzeni, Fabiola, Vollenweider, Cristina F., Kostov, Belchin, Mariette, Xavier, Ramos-Casals, Manuel, Rheumatology Unit, Cordoba (Institute University of Biomedical Sciences University of Cordoba (IUCBC), Autoimmune Diseases Unit, Barcelona (Department of Medicine), Department of Immunology [Debrecen, Hungary], University of Debrecen [Hungary], Oklahoma Medical Research Foundation, Medical Research Foundation, Center for Immunology of Viral Infections and Autoimmune Diseases, Le Kremlin Bicêtre, Department of Rheumatology, Skane University Hospital, Department of Rheumatology and Immunology, Hefei, Anhui, Rheumatology Unit (Rheum Unit - PISA), University of Pisa - Università di Pisa, Rheumatology [CHU Strasbourg], CHU Strasbourg, Clinical Immunology & Rheumatology, Vellore, UO Complessa Reumatologia, Rome, Rheumatology Clinic, Udine (DSMB), Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán - National Institute of Medical Science and Nutrition Salvador Zubiran [Mexico], University Medical Center [Utrecht], Division of Rheumatology, Seoul (Department of Internal Medicine), Unit of Experimental Rheumatology, Stockhom (Department of Medicine), Département de Médecine interne [Lariboisière], Université Paris Diderot - Paris 7 (UPD7)-Hôpital Lariboisière-Fernand-Widal [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), University and Azienda Ospedaliera of Perugia, Autoimmune Systemic Diseases Unit, Barcelona (Department of Internal Medicine), Division of Rheumatology Kanazawa University Graduate School of Medicine, Kanazawa, Centre for Rheumatology and Connective Tissue Diseases (University College London, Royal Free Hospital), Centre for Rheumatology - London, The Queen Elizabeth Hospital, Adelaide, Department of Medical Sciences, Uppsala (Section of Rheumatology), Autoimmune Diseases Department, Madrid, Wroclaw Medical University, University of Groningen [Groningen], Department of Radiology and Cancer Biology, Nagasaki, Department of Medicine, Universidade Federal do Espirito Santo, Vitoria, University of L'Aquila [Italy] (UNIVAQ), CHRU Brest - Service de Rhumatologie (CHU - BREST - Rhumato), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Lymphocyte B et Auto-immunité (LBAI), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO), Hals-Nasen-Ohrenklinik und Poliklinik, Munchen, The William Harvey Research Institute, Barts and The London School of Medicine, Queen Mary University of London (QMUL), Université Fédérale de São Paulo (Unifesp), University of Bergen (UiB), New York University Langone Medical Center (NYU Langone Medical Center), NYU System (NYU), Department of Internal Medicine. Faculty of Medicine. University of São Paulo-RP, Département de Rhumatologie[Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Lapeyronie, Rheumatology Department, Cairo, Rheumatology Unit, Milano (ASST Fatebenefratelli-Sacco), Rheumatology, Buenos Aires, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Universitat de Barcelona (UB), Université Paris-Sud - Paris 11 (UP11), CELLEX-IDIBAPS Department of Autoimmune Diseases, Barcelona, Michel, Geneviève, Hôpital Lariboisière-Fernand-Widal [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), Lymphocytes B, Autoimmunité et Immunothérapies (LBAI), and Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-LabEX IGO Immunothérapie Grand Ouest-Institut Brestois Santé Agro Matière (IBSAM)

Subjects
[SDV] Life Sciences [q-bio], [SDV]Life Sciences [q-bio], ComputingMilieux_MISCELLANEOUS
Abstract

International audience

Published
2017

48. Transancestral mapping and genetic load in systemic lupus erythematosus

Author

Langefeld, C. D., Ainsworth, H. C., Kelly, J. A., Comeau, M. E., Marion, M. C., Howard, T. D., Ramos, P. S., Croker, J. A., Morris, D. L., Sandling, J. K., Almlöf, J. C., Pons-Estel, Bernardo A., Pope, Janet, Raj, Prithvi, Ramsey-Goldman, Rosalind, Reveille, John D., Russell, Laurie P., Sabio, José Mario, Aguilar-Salinas, Carlos A., Scherbarth, Hugo R., Scorza, Raffaella, Seldin, Michael F., Sjowall, Christopher, Svenungsson, Elisabet, Thompson, Susan D., Toloza, Sergio M. A., Truedsson, Lennart, Tusie-Luna, Teresa, Vasconcelos, C., Vilá, Luis M., Wallace, Daniel J., Weisman, Michael H., Wither, Joan E., Bhangale, Tushar, Oksenberg, Jorge R., Rioux, John D., Gregersen, Peter K., Syvanen, Ann-Christine, Ronnblom, Lars, Criswell, Lindsey A., Jacob, Chaim O., Sivils, Kathy L., Tsao, Betty P., Schanberg, Laura E., Behrens, Timothy W., Silverman, Earl D., Alarcón-Riquelme, M. E., Kimberly, Robert P., Harley, John B., Wakeland, Edward K., Graham, Robert R., Gaffney, P. M., Vyse, Timothy J., Acevedo-Vásquez, E. M., Alarcón, G. S., Babini, A. M., Baca, V., Bengtsson, A. A., Berbotto, G. A., Bij, l. M., Brown, E. E., Brunner, H.I., Cardiel, Mario H., Catoggio, Luis, Cervera, Ricard, Cucho-Venegas, Jorge M., Dahlqvist, Solbritt Rantapaa, D'Alfonso, Sandra, Da Silva, Berta Martins, de la Rua Figueroa, Inigo, Doria, Andrea, Edberg, Jeffrey C., Endreffy, Emoke, Esquivel-Valerio, Jorge A., Fortin, Paul R., Freedman, Barry I., Frostegård, Johan, García, Mercedes A., García de la Torre, Ignacio, Gilkeson, G. S., Gladman, Dafna D., Gunnarsson, Iva, Guthridge, Joel M., Huggins, Jennifer L., James, Judith A., Kallenberg, Cees G. M., Kamen, D. L., Karp, David R., Kaufman, Kenneth M, Kottyan, Leah C., Kovacs, Laszlo, Laustrup, Helle, Lauwerys, Bernard R., Li, Quan-Zhen, Maradiaga-Cecena, Marco A., Martín, J., McCune, Joseph M., McWilliams, David R, Merrill, Joan T, Miranda, Pedro, Moctezuma, Jose F., Nath, Swapan K., Niewold, Timothy B., Orozco, Lorena, Ortego-Centeno, N., Petri, Michelle, Pineau, Christian A., National Institute for Health Research (UK), Arthritis Research UK, Alliance for Lupus Research, Junta de Andalucía, National Institute of Arthritis and Musculoskeletal and Skin Diseases (US), National Institutes of Health (US), RILITE Foundation, and Genentech Foundation

Subjects
skin and connective tissue diseases
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 (similar to 50% of these regions have multiple independent associations); these include 24 novel SLE regions (P < 5 x 10(-8)), refined association signals in established regions, extended associations to additional ancestries, and a disentangled complex HLA multigenic effect. The risk allele count (genetic load) exhibits an accelerating pattern of SLE risk, leading us to posit a cumulative hit hypothesis for autoimmune disease. Comparing results across the three ancestries identifies both ancestry-dependent and ancestry-independent contributions to SLE risk. Our results are consistent with the unique and complex histories of the populations sampled, and collectively help clarify the genetic architecture and ethnic disparities in SLE., We gratefully acknowledge the Alliance for Lupus Research for funding and support. The research was supported in part by awards from the Arthritis Research UK Special Strategic Award (ref. 19289) and from George Koukis (T.J.V.). In addition, the research was funded/supported by the National Institute for Health Research (NIHR) Biomedical Research Centre based at Guy's and St Thomas' NHS Foundation Trust and King's College London (T.J.V.). The work would not be possible without funding from the NIH grants AR049084 (RPK, EEB); the International Consortium on the Genetics of Systemic Lupus Erythematosus (SLEGEN) AI083194 (J.B.H.); CA141700, AR058621 Proyecto de Excelencia, Consejeria de Andalucia (M.E.A.R.); AR043814 and AR-065626 (B.P.T.); AR060366, MD007909, AI107176 (S.K.N.); AR-057172 (C.O.J.); RC2 AR058959, U19 A1082714, R01 AR063124, P30 GM110766, R01 AR056360 (P.M.G.); P60 AR053308 (L.A.C.), MUSC part is from UL1RR029882 (G.S.G., D.L.K.) and 5P60AR062755 (G.S.G., D.L.K., P.R.R.). Oklahoma Samples U19AI082714, U01AI101934, P30GM103510, U54GM104938 and P30AR053483 (J.A.J., J.M.G.); Northwestern P60 AR066464 and 1U54TR001018 (R.R.G.); This study was supported by the US National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health (NIH) under Award Numbers K01 AR067280 and P60 AR062755 (PSR); N01AR22265 (funded collection of APPLE samples) (LES) and the APPLE Investigators; R01AR43727, NIH AR 043727 and 069572 (M.P.); NIAMS/NIH P50-AR055503 (D.R.K.). We would like to also thank the RILITE foundation for financial support (C.D.L.). Additional funding for Immunochip genotyping was provided by Genentech.

Published
2017

49. Validation of EULAR primary Sjogren's syndrome disease activity (ESSDAI) and patient indexes (ESSPRI)

Author

Seror, Raphaèle, Theander, Elke, Brun, Johan G, Ramos-Casals, Manel, Valim, Valeria, Dörner, Thomas, Bootsma, Hendrika, Tzioufas, Athanasios, Solans-Laqué, Roser, Mandl, Thomas, Gottenberg, Jacques-Eric, Hachulla, Eric, Sivils, Kathy L, Ng, Wan-Fai, Fauchais, Anne-Laure, Bombardieri, Stefano, Valesini, Guido, Bartoloni, Elena, Saraux, Alain, Tomsic, Matija, Sumida, Takayuki, Nishiyama, Susumu, Caporali, Roberto, Kruize, Aike A, Vollenweider, Cristina, Ravaud, Philippe, Vitali, Claudio, Mariette, Xavier, Bowman, Simon J, EULAR Sjögren's Task Force, Service de rhumatologie, AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), Department of Rheumatology, Lund University [Lund], Klinik für Dermatologie, Venerologie und Allergologie, Department of Pathophysiology, Medical School, University of Athens, Immuno-Rhumatologie Moléculaire, Université de Strasbourg ( UNISTRA ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Université de Lille, Droit et Santé, University of Northumbria at Newcastle [United Kingdom], Service de Médecine interne A et polyclinique médicale [CHU Limoges], CHU Limoges, Department of Internal Medicine, Lupus Clinic, Sapienza University [Rome], Immunologie et Pathologie ( EA2216 ), Université de Brest ( UBO ) -IFR148, Centre d'Investigation Clinique ( CIC - Brest ), Université de Brest ( UBO ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Faculty of Chemistry and Chemical Technology, University of Ljubjana, University of Tsukuba, Equipe 5 : METHODS - Méthodes de l’évaluation thérapeutique des maladies chroniques ( CRESS - U1153 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité ( CRESS (U1153 / UMR_A 1125) ), Institut National de la Recherche Agronomique ( INRA ) -Université Sorbonne Paris Cité ( USPC ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Institut National de la Recherche Agronomique ( INRA ) -Université Sorbonne Paris Cité ( USPC ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Department of Internal Medicine and section of Rheumatology, Villamarina Hospital, Immunologie des Maladies Virales et Autoimmunes ( IMVA - U1184 ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Paris-Sud - Paris 11 ( UP11 ) -Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Immunologie et Pathologie (EA2216), Université de Brest (UBO)-IFR148, Centre d'Investigation Clinique (CIC - Brest), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM), Equipe 5 : METHODS - Méthodes de l’évaluation thérapeutique des maladies chroniques (CRESS - U1153), Université Paris Descartes - Paris 5 (UPD5)-Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), Institut National de la Recherche Agronomique (INRA)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Recherche Agronomique (INRA)-Université Paris Diderot - Paris 7 (UPD7)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Immunologie des Maladies Virales et Autoimmunes (IMVA - U1184), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Sud - Paris 11 (UP11)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Recherche Agronomique (INRA)-Université Paris Descartes - Paris 5 (UPD5)-Université Sorbonne Paris Cité (USPC)-Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Recherche Agronomique (INRA)-Université Sorbonne Paris Cité (USPC), Università degli Studi di Roma 'La Sapienza' = Sapienza University [Rome] (UNIROMA), University of Ljubljana, Université de Tsukuba = University of Tsukuba, Université Paris-Sud - Paris 11 (UP11)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Strasbourg (UNISTRA), Università degli Studi di Roma 'La Sapienza' = Sapienza University [Rome], Université Paris Diderot - Paris 7 (UPD7)-Université Sorbonne Paris Cité (USPC)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Recherche Agronomique (INRA)-Université Paris Diderot - Paris 7 (UPD7)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Recherche Agronomique (INRA), Université Paris-Sud - Paris 11 (UP11)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), and Translational Immunology Groningen (TRIGR)

Subjects
Male, [SDV]Life Sciences [q-bio], Sjögren's Syndrome, Severity of Illness Index, law.invention, RESPONSIVENESS, Randomized controlled trial, law, EUROPEAN LEAGUE, Immunology and Allergy, Prospective Studies, Disease Activity, Outcomes research, Non-U.S. Gov't, Prospective cohort study, Fatigue, primary Sjögren ’ s syndrome, Research Support, Non-U.S. Gov't, Middle Aged, 3. Good health, Europe, Sjogren's Syndrome, REPORTED INDEX, [SDV.MHEP.RSOA]Life Sciences [q-bio]/Human health and pathology/Rhumatology and musculoskeletal system, Female, Adult, medicine.medical_specialty, Immunology, Pain, Research Support, CONTROLLED-TRIAL, Xerostomia, General Biochemistry, Genetics and Molecular Biology, [ SDV.MHEP.RSOA ] Life Sciences [q-bio]/Human health and pathology/Rhumatology and musculoskeletal system, Rheumatology, Internal medicine, Severity of illness, Xerophthalmia, medicine, Journal Article, Humans, Validation Studies, RITUXIMAB, Aged, [ SDV ] Life Sciences [q-bio], business.industry, Gold standard, Construct validity, Reproducibility of Results, HEALTH-STATUS INSTRUMENTS, medicine.disease, Physical therapy, Self Report, business, Rheumatism
Abstract

Objectives To validate the two recently developed disease activity indexes for assessment of primary Sjogren's syndrome (SS): the European League Against Rheumatism (EULAR) SS Patient Reported Index (ESSPRI) and the EULAR SS Disease Activity Index (ESSDAI).Methods A prospective international 6-month duration validation study was conducted in 15 countries. At each visit, physicians completed ESSDAI, SS disease activity index (SSDAI), Sjogren's Systemic Clinical Activity Index (SCAI) and physician global assessment (PhGA); and patients completed ESSPRI, Sicca Symptoms Inventory (SSI), Profile of Fatigue and Discomfort (PROFAD) and patient global assessment (PGA). Psychometric properties (construct validity, responsiveness and reliability) were evaluated and compared between scores.Results Of the 395 patients included, 145 (37%) and 251 (64%) had currently active or current or past systemic manifestations, respectively. EULAR scores had higher correlation with the gold standard than other scores (ESSDAI with PhGA: r= 0.59; ESSRPI with PGA: r= 0.70). Correlations between patient and systemic scores were very low (ranging from 0.07 to 0.29). All systemic scores had similar large responsiveness in improved patients. Responsiveness of patient scores was low but was significantly higher for ESSPRI compared with SSI and PROFAD. Reliability was very good for all scores.Conclusions ESSDAI and ESSPRI had good construct validity. All scores were reliable. Systemic scores had a large sensitivity to change in patients whose disease activity improves. Patient scores had a small sensitivity to change, however, significantly better for ESSPRI. Systemic and patient scores poorly correlated, suggesting that they are 2 complementary components that should be both evaluated, but separately.

Published
2014
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