Neoantigenic group on Fc fragments in rheumatoid arthritis synovial fluids

Expression of neoantigens during denaturation of IgG by oxygen radicals or proteolysis was assumed to be a possible mechanism for stimulation of rheumatoid factor (RF) formation and/or granulocyte dependent inflammative joint destruction. The so-called human leukocyte elastase (HLE) regularly released by stimulated neutrophils f.e. into the RA synovial fluid is known to split IgG in vitro into papain like fragments and low molecular weight peptides. The n-terminal site of the HLE related Fc is bearing a neoantigenic group which is located near the hinge region but not expressed by the native IgG. The neoantigen itself is represented by the low molecular weight peptides produced by prolonged HLE-IgG proteolysis. Detection of HLE generated Fc in synovial fluids was performed by radioimmunoassay specific for the neoantigen. Patients were divided into the three groups; I RA (n = 23), II inflammative joint effusions except RA (n = 23), III osteoarthritis and trauma (n = 19). The biological effect of the neoantigen on to granulocyte oxidative metabolism was tested by Cytochrome C reduction and chemiluminescence. Neoantigen bearing Fc could be detected in 15 of 23 cases of group I, in group II in 11 of 23 cases and only in 7 of 19 cases in group III. The median concentrations were 0.62 micrograms in group I and zero in II and III. The HLE derived Fc were able to inhibit the oxidative metabolism of activated granulocytes in vitro. The O2- production of stimulated granulocytes was depressed dose dependent by the neoantigen. The neoantigenic group itself does not react with RF as proved by nephelometric titration of HLE derived Fc, neoantigenic peptide and native IgG against a RF standard.