Heterogeneous Nuclear Ribonucleoprotein H1, a Novel Nuclear Autoantigen

BACKGROUND: Serum samples from patients with autoimmune connective tissue diseases that show a finely speckled antinuclear antibody (ANA) on indirect immune-fluorescence often have antibodies against unknown nuclear target antigens. To search for such autoantigens we applied a proteomic approach using sera from patients with a high ANA titer (>= 640) and Finely speckled fluorescence but in whom no antibodies to extractable nuclear antigens (ENA) could be identified. METHODS: Using an immunoproteomics approach we identified heterogeneous nuclear ribonucleoprotein HI (hnRNP HI) as a novel nuclear target of autoantibody response. RESULTS: Recombinant rat hnRNP H I reacted in Western blot analyses with 48% of 93 sera from patients with primary Sjogren syndrome and with 5.2% of 153 sera from patients with other connective tissue diseases (diseased controls). For comparison, the diagnostic sensitivity and specificity of anti-Sjogren syndrome A (SSA) antibodies for primary Sjogren syndrome in the same patient cohort were 88.2% and 76.3%, respectively. Interestingly, 5 of 11 primary Sjogren syndrome patients with no anti-SSA or anti-SSB antibodies had anti-hnRNP HI antibodies. Anti-hnRNP H1 antibodies were preabsorbed by hnRNP H1, as demonstrated by indirect immunofluorescence. In an evaluation of the presence of anti-hnRNP H I antibodies in 188 consecutive samples submitted to the clinical laboratory with positive ANA (titer >= 160), anti-hnRNP H1 antibodies were found in 3 of 7 (2 primary and 5 secondary) Sjogren syndrome patients and in 8.3% of the diseased controls. CONCLUSIONS: HnRNP H1 is a newly discovered autoantigen that could become an additional diagnostic marker. (C) 2009 American Association for Clinical Chemistry