Neue Autoantikörper in der Diagnostik der rheumatoiden Arthritis

Abstract

The diagnosis of rheumatoid arthritis has been hampered by the lack of a truly disease-specific serologic marker. Thus, despite its moderate specificity rheumatoid factor (RF) is still the only established marker antibody for RA and among the diagnostic criteria of the American College of Rheumatology the only serologic one. However, in recent years, several newly characterized autoantibodies have been described that may have the potential to become diagnostic indicators for RA. In particular, antibodies to citrullinated targets (anti-keratin or anti-filaggrin antibodies, respectively, antibodies to synthetic citrullinated peptides) appear to be highly specific for RA. Other potentially useful antibodies include anti-RA33 autoantibodies and antibodies to the stress protein BiP which seem to have higher specificity for RA than RF. Apart from being promising diagnostic markers these autoantibodies or the underlying cellular autoimmune reactions, respectively, may also play a role in the pathogenesis of RA.

Mass Spectrometric and Peptide Chip Epitope Mapping of Rheumatoid Arthritis Autoantigen RA33

“…HnrNP proteins are associated with pre-mrNAs in the nucleus in complex 4 which forms part of the spliceosome. 6 they are involved in pre-mrNA processing and other aspects of mrNA metabolism and transport.…”

“…In conjunction with anticcP antibody level determination, measuring antirA33 autoantibody levels in rA patients and in other autoimmune patients has become important, in particular for diagnosing rA in the absence of rf and for estimating the severity of the disease. 6,7 Predicting the severity of disease development is directing on-going and future therapy.…”

A Novel Mass Spectrometric Epitope Mapping Approach without Immobilization of the Antibody

“…Similarly, the RA33 auto-antigen, present in rheumatic autoimmune diseases, carries its name according to its migration behavior in sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE), and has been found to be identical to the protein named hnRNP A2/B1 (RefSeq accessions NP_002128 and NP_112533; Uniprot Accession number P22626). HnRNP proteins are associated with pre-mRNAs in the nucleus in complex 4 which forms part of the spliceosome (Steiner and Smolen, 2002). They are involved in pre-mRNA processing and other aspects of mRNA metabolism and transport.…”

“…Therefore they can provide diagnostic help early in disease, particularly when Rheumatoid factor (RF) is negative in patient samples. In conjunction with anti-cyclic citrullinated peptide antibody (antiCCP antibody) level determination, measuring anti-RA33 autoantibody levels in RA patients and in other autoimmune patients has become important in particular for diagnosing RA in the absence of RF and for estimating severity of the disease (Feist et al, 2007;Steiner and Smolen, 2002). As both proteins play their roles in autoimmune diseases it is of interest to identify epitopes to which autoantibodies from individual patients are directed.…”