Spliceosomal
small nuclear ribonucleoproteins (U-snRNPs) are frequent and specific targets of
autoantibodies in systemic
rheumatic diseases. The abundant, functionally related
heterogeneous nuclear ribonucleoprotein complexes (hnRNPs) have later defined as a new target of
autoantibodies, of which their immunochemical/immunogenic and pathogenic properties are still under investigation. Among
hnRNP proteins, those belonging to the A/B type are considered as the major
autoantigens targeted by
antibodies in sera of patients suffering with
rheumatoid arthritis (RA),
systemic lupus erythematosus (SLE) and
mixed connective tissue disease (
MCTD). By performing an extensive screening using rat liver 40S
hnRNP antigenic material, we document here the existence of multiple specificities of anti-
hnRNP A/B
autoantibodies in sera of Greek patients suffering with a spectrum of systemic
rheumatic diseases. This included patients with SLE,
Sjogren's syndrome (SS), Scleroderma (SSc) and a specific group of patients mostly with undifferentiated disease (UD patients). In total, four distinct types of anti-
hnRNP A/B
autoantibodies have been recognized. The first two referred to the known anti-hnRNPA2(RA33) and anti-
hnRNP A1; the latter appearing very rarely. The third was of the new type selectively reacting with
hnRNP B2 and an
hnRNP A3 variant, while the fourth was a rare case of anti-
hnRNP B2 alone. In addition, a novel specificity of
autoantibodies against
hnRNP L protein was identified in association with anti-
hnRNP A/B
antibodies. The co-existence within a serum of
autoantibodies having variable specificity for
hnRNP A/B and L
autoantigens was shown. Specific immunochemical features of the identified
autoantibodies are presented and a possible mechanism of autoepitope spreading within
protein components of
hnRNP complexes is discussed.