Autoantibodies to the translational suppressors T cell intracytoplasmic antigen 1 and T cell intracytoplasmic antigen 1–related protein in patients with rheumatic diseases: Increased prevalence in systemic lupus erythematosus and systemic sclerosis and correlation with clinical features
✍ Scribed by Esther Jimenez-Boj; Nancy Kedersha; Makiyeh Tohidast-Akrad; Franz M. Karlhofer; Georg Stummvoll; Christof Zimmermann; Walter Ulrich; Serena Guiducci; Elisabeth Hoefler; Martin Aringer; Georg Schett; Marco Matucci-Cerinic; Josef S. Smolen; Günter Steiner
- Publisher
- John Wiley and Sons
- Year
- 2008
- Tongue
- English
- Weight
- 850 KB
- Volume
- 58
- Category
- Article
- ISSN
- 0004-3591
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✦ Synopsis
Abstract
Objective
T cell intracytoplasmic antigen 1 (TIA‐1) and TIA‐1–related protein (TIAR) are involved in posttranscriptional regulation of the expression of tumor necrosis factor α (TNFα) and other proteins. Given the pivotal role of TNFα in chronic inflammatory diseases, this study was undertaken to analyze sera from patients with systemic autoimmune diseases for the presence of autoantibodies to TIA proteins and to investigate the expression of these proteins in inflamed tissue.
Methods
The presence of autoantibodies to TIA proteins in sera from 385 patients with rheumatic diseases and healthy controls was determined by immunoblotting using recombinant antigens. Expression of TIA proteins in skin and kidney tissue was analyzed by immunohistochemistry. Serum levels of TNFα were measured by enzyme‐linked immunosorbent assay.
Results
Autoantibodies to TIA‐1 and/or TIAR were detected in 61% of patients with systemic lupus erythematosus (SLE), 42% of patients with systemic sclerosis (SSc), 15–31% of patients with other rheumatic diseases, and 6% of healthy controls. Compared with patients negative for anti‐TIA antibody, anti‐TIA antibody–positive SLE patients had higher disease activity (P = 0.01), elevated antibodies to double‐stranded DNA (P = 0.0003), and increased serum TNFα levels (P = 0.018). In SLE patients, anti‐TIAR antibodies were associated with lupus nephritis (P = 0.02), while in patients with SSc, anti–TIA‐1 was associated with lung involvement (P = 0.02). Immunohistochemical analysis of skin and kidney tissue revealed aberrant expression of TIA proteins in skin lesions from SLE and SSc patients, as well as in glomerular cells from SLE patients.
Conclusion
Aberrant expression of TIA proteins in inflammatory tissue may lead to systemic autoantibody responses, particularly in SLE and SSc. Increased occurrence of anti‐TIA autoantibodies in patients with severe organ involvement may point to a possible pathogenetic role.