Heterogeneous nuclear ribonucleoprotein (
hnRNP) complexes are major constituents of the spliceosome. They are composed of approximately 30 different
proteins which can bind to nascent
pre-mRNA. Among these, the
hnRNP-A/B proteins form a subgroup of highly related
proteins consisting of two adjacent RNA binding domains (RBD) within the N-terminal parts, whereas the C-terminal halves contain almost 50%
glycine residues. These
proteins, in particular A2/RA33, are targeted by
autoantibodies from patients with
rheumatoid arthritis (RA),
systemic lupus erythematosus (SLE), and
mixed connective tissue disease (
MCTD). In SLE anti-
hnRNP antibodies frequently occur together with
antibodies to U1
small nuclear RNP (U1-snRNP) and Sm, other
proteins of the spliceosome. Preliminary
epitope mapping studies have revealed major antibody binding sites in the
RNA binding regions for all three diseases. Nevertheless, there is some indication of disease specific
epitope recognition. Studies in animal models have demonstrated anti-RA33/
hnRNP-A/B
antibodies in lupus-prone mouse strains. Thus,
autoantibodies to the spliceosomal
hnRNP-A/B proteins are a common feature of RA, SLE, and
MCTD. However, these diseases differ in their reactivities to other spliceosomal
proteins, especially anti-U1
snRNP and Sm. Therefore, anti-RA33/
hnRNP-A/B
autoantibodies are not only valuable diagnostic markers but may also allow additional insights into the pathogenesis of rheumatic
autoimmune diseases.