This study investigates specificity, sensitivity and concomitant presence of antibodies against histone H1 (H1), nucleosomes (NUC), chromatin (CHR) and dsDNA in patients with systemic lupus erythematosus (SLE), analyses their association with SLE disease activity and characterizes the immunodominant epitope reactivity of anti-H1 antibodies and its relation to SLE disease activity. In a cross-sectional study 394 sera of patients with various rheumatic diseases and healthy subjects were analysed by ELISA for antibodies against H1, NUC, CHR and dsDNA. In addition, a longitudinal analysis was performed that included 121 sequential serum samples derived from 16 SLE patients to assess the relation of these antibodies as well as antibodies to histone H2B to SLE disease activity. To assess epitope reactivity of anti-H1 antibodies overlapping synthetic peptides covering the entire H1 sequence were used. Anti-H1 antibodies yielded a sensitivity of approximately 45% and a specificity of over 98% for SLE, which was comparable to that found for anti-dsDNA antibodies. Anti-CHR and anti-NUC antibodies were of similar sensitivity but slightly (anti-CHR) or considerably (anti-NUC) less specific for SLE (95 and 85%, respectively). The sequential analysis revealed a strong correlation of anti-H1 antibodies with SLE disease activity that was better than the correlation of anti-dsDNA and anti-NUC antibodies, while only weak correlation was found for anti-CHR and anti-H2B antibodies. The immunodominant epitope for anti-H1 was localised between amino acids 204 and 218 (pp204–218) and immune reactivity to this epitope also correlated with disease activity. Anti-H1 is a highly specific marker for SLE with a diagnostic value comparable to anti-dsDNA. A positive testing for anti-H1 indicates increased disease activity, as does the appearance of antibodies to its immunodominant epitope pp204–218.

Testing for RF subtypes did not provide additional diagnostic information. Patients positive for RF50 and/or ACPA had an unfavourable prognosis, irrespectively of changes in the antibody profile during follow-up, whereas anti-RA33 positivity was inversely associated with erosiveness at baseline and at later time points.

Peptide p155-175 encompasses a disease-specific immunodominant epitope of hnRNP-A2. Since antibodies to p155-175 correlate with disease activity and nephritis, they may be useful as markers for active SLE.

Histone H1 constitutes a major B cell and T cell autoantigen in SLE, triggering a proinflammatory Th1 response and driving autoantibody production. This suggests that histone H1 may be of considerable relevance for the pathogenesis of SLE.

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.