Title |
Discerning Risk of Disease Transition in Relatives of Systemic Lupus Erythematosus Patients Utilizing Soluble Mediators and Clinical Features
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Published in |
Arthritis & Rheumatology, February 2017
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DOI | 10.1002/art.40004 |
Pubmed ID | |
Authors |
Melissa E. Munroe, Kendra A. Young, Diane L. Kamen, Joel M. Guthridge, Timothy B. Niewold, Karen H. Costenbader, Michael H. Weisman, Mariko L. Ishimori, Daniel J. Wallace, Gary S. Gilkeson, David R. Karp, John B. Harley, Jill M. Norris, Judith A. James |
Abstract |
Systemic lupus erythematosus (SLE) and other autoimmune diseases cause significant morbidity. Identifying populations at risk of developing SLE is essential to curtail irreversible inflammatory damage. The objective of this study was to identify factors associated with transition to classified disease that inform SLE risk. Previously identified lupus patient blood relatives with < 4 American College of Rheumatology SLE classification criteria at baseline (n=409) were enrolled in this follow-up study. Participants provided detailed family, demographic, and clinical information, including the SLE-specific portion of the Connective Tissue Disease Screening Questionnaire (SLE-CSQ). Plasma samples were tested for the presence of lupus-associated autoantibodies and 52 soluble mediators. Generalized estimating equations (GEE) were applied to identify factors anticipating disease transition. Forty-five relatives (11%) transitioned to classified SLE during follow-up (mean time=6.4 years). Relatives who transitioned displayed more lupus-associated autoantibody specificities and higher SLE-CSQ scores (p<0.0001) at baseline than non-transitioned relatives. Importantly, they also had elevated baseline plasma levels of inflammatory mediators, including B-lymphocyte stimulator (BLyS), stem cell factor (SCF), and interferon-associated chemokines (p≤0.02), with concurrent decreases in levels of regulatory mediators, tumor growth factor (TGF)-β and interleukin (IL)-10 (p≤0.03). GEE revealed that baseline SLE-CSQ or ACR scores and plasma levels of SCF and TGF-β (p≤0.03), but not autoantibodies, were significant and independent predictors of SLE transition. Altered levels of soluble mediators anticipate transition to classified disease in lupus relatives. Thus, immune perturbations precede SLE classification and can help identify high-risk relatives for rheumatology referral and potential enrollment in prevention trials. This article is protected by copyright. All rights reserved. |
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United States | 3 | 25% |
Canada | 1 | 8% |
Chile | 1 | 8% |
Spain | 1 | 8% |
United Kingdom | 1 | 8% |
Bulgaria | 1 | 8% |
Unknown | 4 | 33% |
Demographic breakdown
Type | Count | As % |
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Members of the public | 8 | 67% |
Science communicators (journalists, bloggers, editors) | 2 | 17% |
Scientists | 1 | 8% |
Practitioners (doctors, other healthcare professionals) | 1 | 8% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
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Unknown | 35 | 100% |
Demographic breakdown
Readers by professional status | Count | As % |
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Student > Ph. D. Student | 4 | 11% |
Other | 3 | 9% |
Student > Doctoral Student | 2 | 6% |
Student > Bachelor | 2 | 6% |
Lecturer | 2 | 6% |
Other | 8 | 23% |
Unknown | 14 | 40% |
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Medicine and Dentistry | 9 | 26% |
Immunology and Microbiology | 5 | 14% |
Pharmacology, Toxicology and Pharmaceutical Science | 1 | 3% |
Biochemistry, Genetics and Molecular Biology | 1 | 3% |
Mathematics | 1 | 3% |
Other | 2 | 6% |
Unknown | 16 | 46% |