ANTI-52 KDA RO(SSA) AUTOANTIBODIES IN DIFFERENT AUTOIMMUNE-DISEASES PREFERENTIALLY RECOGNIZE EPITOPES ON THE CENTRAL REGION OF THE ANTIGEN

Objective. Antibodies against the 52 kDa Ro(SSA) protein are an import ant laboratory variable in autoimmune diseases, most notably in the di agnosis of primary Sjogren's syndrome (SS), congenital heart block (CH B), and certain varieties of systemic lupus erythematosus (SLE). Howev er, there is controversy about the differential reactivity of these se ra, both with regard to immunogenic regions on the target protein and the respective antibody liters. Therefore, sera from various autoimmun e diseases were tested against a broad panel of recombinant 52 kDa Ro( SSA) fusion proteins. Methods. Sera were obtained from 20 patients wit h SLE, 10 with primary SS, 15 children with CHB, 6 healthy anti-52 kDa Ro(SSA) positive infants born to mothers with SLE and 7 anti-52 kDa R o(SSA) positive patients with primary biliary cirrhosis/secondary SS. Epitope mapping was performed using different fusion proteins in ELISA and immunoblot. Results. All sera reacted with whole recombinant anti gen as well as with the protein carrying the aminoacid sequence (AA) 1 -245, The proportion of positive sera against the 52 kDa Ro fusion pro teins tested was found in descending order in patients with CHB, down to primary SS, the healthy infants group, patients with SLE and finall y primary biliary cirrhosis/secondary SS, In general, CHB and primary SS sera exhibited the broadest reactivity against the recombinant prot ein compared to the Limited and lower reactivity of sera from patients with primary biliary cirrhosis. Sera from infants with CHB had signif icantly higher antibody levels to AA 1-245 compared to SLE sera (p < 0 .0005) and to sera from healthy infants born to SLE mothers (p < 0.05) , as well as to serum samples from patients with primary biliary cirrh osis/SS (p < 0.005), The strongest antigenicities recognized by anti-5 2 kDa Ro(SSA) autoantibodies are located within the AA 197-245 region that represents an essential epitope. Further antigenic sites preferen tially recognized by SS, CHB, and healthy infant sera are located with in AA 153-195. Conclusion. Thus, the central region AA 153-245 is the major immunogenic region of the 52 kDa Ro(SSA) antigen containing a st rong antigenic epitope between AA 197-245. The antibody response is di rected to this major antigenic region regardless of the underlying aut oimmune disease. However, the strikingly different quantities of antib ody levels and the recognition of epitopes on AA 153-196 may be associ ated with different disease expressions.