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Distinct Functions of Anti-interferon Autoantibodies in Systemic Lupus Erythematosus: A Comprehensive Analysis of Anticytokine Autoantibodies in Common Rheumatologic Diseases.

Research paper by Sarthak S Gupta, Ioanna P IP Tatouli, Lindsey B LB Rosen, Sarfaraz S Hasni, Ilias I Alevizos, Zerai G ZG Manna, Juan J Rivera, Chao C Jiang, Richard M RM Siegel, Steven M SM Holland, Haralampos M HM Moutsopoulos, Sarah K SK Browne

Indexed on: 28 Jan '16Published on: 28 Jan '16Published in: Arthritis & Rheumatology



Abstract

Anticytokine autoantibodies occur across a range of hematologic, pulmonary and infectious diseases, however, systematic investigation of their presence and significance in autoimmune diseases is lacking.Serum samples from patients with systemic lupus erythematosus (SLE) (n=199), primary Sjögren's syndrome (SS) (n=150), rheumatoid arthritis (RA) (n=149) and healthy controls (n=200) were screened for 24 anticytokine autoantibodies using a multiplex bead-based assay. To evaluate biological activity of anticytokine autoantibodies, their ability to block cytokine-induced signal transduction or protein expression was measured. RNA sequencing was performed on whole blood in subset of controls and SLE patients.SLE and SS patients had striking excess of autoantibodies against interferons and the interferon-responsive chemokine interferon-inducible-protein-10 (IP-10). Only autoantibodies against type I interferon, interleukin (IL)-12 and IL-22 exhibited neutralizing activity. In SLE, anti-interferon-γ autoantibodies tracked with more disease activity, anti-double-stranded-DNA antibodies, and elevated expression of interferon-α/β-inducible genes. Conversely, SLE patients with blocking anti-interferon-α autoantibodies normalized their type I interferon gene expression signature. Anti-type III interferons (λ2, λ3), and anti-IP-10 autoantibodies were newly recognized and autoantibodies against macrophage-colony stimulating factor, IL-4, IL-7, IL-17 and IL-22, that have not been previously identified in rheumatologic conditions, were discovered.Anticytokine autoantibodies were associated with distinct patterns of SLE, SS and RA. Anti-interferon autoantibodies were overrepresented in SLE and SS and fall into distinct functional classes with only a subset of anti-type I interferon antibodies exhibiting neutralizing activity. Anti-interferon-γ autoantibodies correlated with increased disease activity and interferon-related gene expression, suggesting that they may contribute to the pathogenesis of SLE. This article is protected by copyright. All rights reserved.