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

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 ␣ (TNF␣) and other proteins. Given the pivotal role of TNF␣ 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 TNF␣ 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 TNF␣ 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.

Selected growth factors and diffusing capacity of the lung for carbon monoxide in patients with systemic lupus erythematosus

“…The significant positive correlation between serum TNF-α and bFGF levels seen in the whole patient group and HRCT-negative subjects and the lack of similar correlation in HRCT-positive patients might support such hypothesis in the light of the role of bFGF in fibrosis [15]. The results concerning the level of TNF-α in our study differ from the earlier ones obtained by other authors who observed increased serum level of this factor in SLE patients [16,17] especially in SLE subjects with pulmonary involvement [17]. The demonstrated differences could be partially explained by lower disease activity in our patients (calculated on the day of blood sampling SLEDAI score was <10 or slightly higher) [18].…”

B cell epitopes of the heterogeneous nuclear ribonucleoprotein A2: identification of a new specific antibody marker for active lupus disease

“…Sera from patients with other rheumatic diseases (n = 147) diagnosed in previous studies according to established clinical criteria7 21 24 and healthy subjects (n = 29) were randomly selected from our serum bank in Vienna (see below for details). The person selecting the samples was not aware of the analyses performed in this study.…”

Autoantibodies in Autoimmune Diseases

“…The T cell intracytoplasmic antigen 1 (TIA-1) is another interesting target for autoantibodies in SLE [70]. An investigation of 385 patients with rheumatic diseases and healthy controls revealed, that 61% of the SLE-patients sera contained anti-TIA-1 antibodies, whereas only 6% of the healthy control sera were positive for this autoantibody.…”

“…Patients with systemic sclerosis exhibit 42% and patients with other rheumatic diseases 15-31% of TIA-1 positive sera. Furthermore, there was an increased occurrence of this autoantibody with severe organ involvement, which might be of prognostic relevance [70].…”