RA33

RA33, also known as heterogeneous nuclear ribonucleoprotein A2/B1 is an autoantigen in human autoimmune diseases.

In 1989, a novel class of autoantibodies were detected in sera of patients with rheumatoid arthritis (RA) which were directed to a protein with an estimated molecular mass of approximately 33 kDa contained in nuclear extracts from HeLa cells [Hassfeld et al.: Demonstration of a new antinuclear antibody (anti-RA33) that is highly specific for rheumatoid arthritis. "Arthritis & Rheumatism 1989" ; 32:1515-20.] . The antigen was therefore given the name RA33. Protein sequencing of highly purified RA33 revealed that it was identical to the hetergoneous nuclear ribonucleoprotein A2 (hnRPA2B1) [Steiner et al.: Purification and partial sequencing of the nuclear autoantigen RA33 shows that it is indistiguishable from the the A2 protein of the heterogeneous nuclear ribonucleoprotein complex. "Journal of Clinical Investigation 1992" ; 90:1061-66] . Nowadays, the name anti-RA33 defines autoantibodies that are directed to hnRNP-A2 and its splice variant hnRNP-B1. Anti-RA33 occur in approximately 30-35% of patients with RA, in 20-25% of patients with systemic lupus erythematosus and in 35-40% of patients with mixed connective tissue disease, being rare or absent in other arthritic conditions with a non-autoimmune etiology [Steiner et al.: Autoantibodies to the A/B proteins of the heterogeneous nuclear ribonucleoprotein complex: Novel tools for the diagnosis of rheumatic diseases. "International Archives of Allergology and Immunology 1996";111:314-19.] . Anti-RA33 can be easily detected by immunoblotting employing crude nuclear extracts or the recombinant antigen. Fo routine diagnostics also ELISA can be employed which is somewhat less sensitive than immunoblotting. The use of indirect immunofluorescence is of limited usefulness for detecting anti-RA33. The pathogenic role of anti-RA33 is not fully understood. Anti-RA33 and T cells directed against RA33, that can be found in about 60% of RA patients might contribute to autoimmune inflammation by immune complex formation or by virtue of secretion of cytokines that may initiate and drive the pathogenic process [Fritsch et al.: Characterization of autoreactive T cells to the autoantigens RA33 (hnRNP A2) and filaggrin in patients with rheumatoid arthritis. "Journal of Immunology 2002" 169:1068-76] . Of note, anti-RA33 are detectable already in the earliest disease stage of RA or even years before the onset of actual clinical disease. The positive predictive value of anti-RA33 is 74%. However, anti-RA33 are not associated with bone erosions or disease activity. In the absence of rheumatoid factor and anti-citrullinated protein antibody they are associated with a milder disease course of RA rather.

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