The autoimmune response to chromatin antigens in systemic lupus erythematosus: autoantibodies against histone H1 are a highly specific marker for SLE associated with increased disease activity

Abstract

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.

Histone H1/MBP hydrolysing antibodies - novel potential marker in diagnosis of disease severity in systematic lupus erythematosus patients

“…Possessing a cross reactivity to different protein autoantigens, these auto-AB can be involved in various mechanisms of pathogenesis, apoptosis of including immunocompetent cells, which is a decisive factor in the development of autoimmune syndrome and the disease in general. It is known that anti-DNA AB of IgG classes of blood serum of SLE patients are also capable of hydrolyzing DNA and different types of RNA (having DNase and RNase activity) [10,11]. It was also found that DNA/RNA hydrolyzing AB (DNAabzymes) possess high cytotoxicity and their level in the blood serum of SLE patients correlates with the disease severity [12,13].…”

“…Hereby, antinuclear auto-AB serves as molecular markers for the disease severity prognosis, as well as for its treatment efficiency [6,7]. Among antinuclear auto-AB especially attract attention anti-DNA AB and antihistone AB [8][9][10]. Possessing a cross reactivity to different protein autoantigens, these auto-AB can be involved in various mechanisms of pathogenesis, apoptosis of including immunocompetent cells, which is a decisive factor in the development of autoimmune syndrome and the disease in general.…”

New Biotechnologycal Approaches for Immunotherapy of Autoimmune Diseases

“…Systemic lupus erythematosus is a complex autoimmune disease characterized by the generation of IgG auto-antibodies specific to nuclear antigens -double-stranded (ds) DNA (42), histones (67), nucleosomes (52), etc. the primary auto-antigen that drives the autoimmune response in Sle is not known.…”

Anticorpos antinucleossomo e síndrome antifosfolipídica: estudo observacional

“…4 The frequency of autoantibodies against nucleosome (anti-NCS) and H1 stripped chromatin (anti-chromatin) in SLE varies from 50%-100% and the specifi city for SLE diagnosis has been reported from 90%-99%. [5][6][7][8][9][10][11][12][13][14][15] Anti-NCS/chromatin antibodies have been associated with active glomerulonephritis in SLE patients. [6][7][8][9][10] Although considered specifi c for SLE, anti-NCS/chromatin antibodies have been reported in other autoimmune conditions such as systemic sclerosis, Sjögren's syndrome, mixed connective tissue disease, and type 1 autoimmune hepatitis.…”

“…[5][6][7][8][9][10][11][12][13][14][15] Anti-NCS/chromatin antibodies have been associated with active glomerulonephritis in SLE patients. [6][7][8][9][10] Although considered specifi c for SLE, anti-NCS/chromatin antibodies have been reported in other autoimmune conditions such as systemic sclerosis, Sjögren's syndrome, mixed connective tissue disease, and type 1 autoimmune hepatitis. 6,8,9,16,17 There is some controversy in the literature and some authors believe that the fi nding of positive reactivity in non-lupus patients is due to heterogeneity in NCS/chromatin preparations and other reagents used in enzyme-linked immunosorbent assay (ELISA) tests.…”