Rheumatoid arthritis (RA) is characterized by the occurence of autoreactive antibodies and T cells. RA is heterogneous disease also with respect to these autoreactivities, since none of them is present in every RA patient and they are additionally also present - although to a considerably lesser extent - in other autoimmune diseases and even in healthy individuals. It has now been analyzed if there are clusters of autoreactivites that are absolutely specific for RA.
Therefore, the RA-associated autoantigens RA33 (hnRNP A2), cit-rulline, rheumatoid factor (RF), the stress protein BiP (heavy chain binding protein), calpastatin (Calp) and calreticulin (Calr) have either been biochemically purified or used as a kit of of recombinant antigen or chemically synthesized peptides. These antigens have been applied to screen sera and PBMCs from RA and control patients for reactivity and the data have subsequently been subjected to cluster analyses.
Analyzing the reactivities of 100 RA and 100 control patients, the following patterns of the three combined autoreactivities were determined to be absolutly specific for RA: RF+Cit+BiP+, RF-Cit+BiP+. RA-specific patterns composed of four autoreactivities are RA33+RF+Cit+BiP+, RA33-RF+Cit+BiP+, RA33+RF+Cit+ BiP-, RA33+RF-Cit+BiP+, RA33+RF+Cit-BiP+, RA33-RF+Cit-BiP+. RA-specific patterns composed of five autoreactivites are RA33+RF+Cit+BiP+Calp+, RA33-RF+Cit+BiP+Calp+, RA33+ RF+Cit+BiP-Calp+, RA33+RF-Cit+BiP+Calp+, RA33+RF+ Cit+BiP+Calp-, RA33+RF+Cit+BiP-Calp-. RA-specific autoreactiv-ities composed of six autoreactivities are RA33+RF+ Cit+BiP+Calp+Calr+, RA33-RF+Cit+BiP+Calp+Calr+, RA33+ RF+Cit+BiP-Calp-Calr+, RA33-RF+Cit+BiP-Calp+Calr+, RA33-RF+Cit-BiP-Calp+Calr-. Other patterns also occured exclusively in RA patients, but the differences did not reach statistical significance. Patterns including p205-reactivity have yet to be analyzed and will be presented. Summing up the RA-specific patterns that are complementary to each other, the sensitivity of the analysis for RA is 54%.
It appears evident that analyzing other known and unknown RA-associated autoantigens will further increase the sensitivity of the autoreactivity cluster analysis. The diagnostic confidence will markedly improve by testing autoreactivity patterns that clearly distinguish RA from other rheumatic diseases. The composition of the autoreactivity patterns will also improve our understanding of the pathogenesis.