[en] BACKGROUND: Heterogeneous nuclear ribonucleoproteins (hnRNP) are abundant nucleoplasmic pre-mRNA-binding proteins. The aim of this study was to unravel the mosaic of autoantibodies to hnRNP's in systemic rheumatic diseases. METHODS: Recombinant human hnRNP A1, B1, C1, E1, F, Gi, H1, I, K, and P2 were prepared. Antibodies to these antigens were determined by Western blotting and ELISA (for hnRNP B1, E1, F, and H1) in controls (chronic fatigue syndrome) and in patients with various connective tissue disorders. RESULTS: Western blotting analysis on 106 controls and 298 patients with a connective tissue disorder revealed that antibodies to all tested hnRNP antigens, except hnRNP Gi, were significantly more prevalent in Sjogren's syndrome (SS) than in controls. The highest reactivity was found for hnRNP B1, E1, F, and H1 (reactivity in >45% of patients with SS and in 2.8% of controls). Reactivity to hnRNP B1, E1, F, and H1 was also evaluated by ELISA in controls and in 228 patients with a connective tissue disease. Reactivity to at least 2 of the 4 tested antigens was found in 1.1% of controls, 16% of patients with systemic lupus erythematosus (SLE), and 18% of patients with SS. Reactivity to at least 3 of the 4 antigens was found in none of the controls, in 3.2% of patients with SLE, and in 15% of patients with SS. CONCLUSIONS: several hnRNP's are target antigens in SS. The combined presence of antibodies to several hnRNP's was strongly associated with connective tissue disease in general and SS in particular.