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: their N-terminal halves consist of two adjacent RNA-binding domains, whereas the C-terminal halves contain almost 50%
glycine residues. These
proteins represent a group of novel
autoantigens which are targeted by
autoantibodies from patients with
rheumatoid arthritis (RA),
systemic lupus erythematosus (SLE), and
mixed connective tissue disease (
MCTD): thus, anti-A2/RA33
autoantibodies target the
hnRNP proteins A2, B1, B2 (the 'RA33 complex'), and anti-A1
autoantibodies are directed to the
hnRNP proteins A1 and A1b. In SLE, anti-
hnRNP-A/B
antibodies frequently occur together with
antibodies to two other spliceosome-associated
antigens, U1
small nuclear RNP (U1-snRNP) and Sm.
Epitope-mapping studies have revealed that the major antibody binding sites are located in the
RNA-binding regions. Furthermore, there is some indication of disease-specific
epitope recognition. Studies in animal models have demonstrated the presence of anti-
hnRNP-A/B
antibodies in several 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 components, such as U1-snRNP and Sm
antigens. Therefore, anti-
hnRNP-A/B
autoantibodies are not only valuable diagnostic markers but may also allow additional insights into the pathogenetic mechanisms of rheumatic
autoimmune diseases.