Rheumatoid Arthritis: Milosević-Jovcić N

Cirić D, Milosević-Jovcić N, Ilić V, Petrović S. · Institute for Medical Research, Belgrade, Serbia and Montenegro. · Autoimmunity. · Pubmed #16278145 No free full text.

Abstract: Although IgG with reduced content of galactose has been implicated as important in the autoimmune rheumatoid factor (RF) response in rheumatoid arthritis (RA), relatively little is known about the temporal relationship between RF and the degree of galactosylation of IgG in vivo. We established an experimental model for studying the dynamic association between changes in the relative extent of galactosylation of IgG antigen(s) and the main parameters of RF activity, such as the titer, specificity and functional affinity/avidity. Rabbits hyperimmunized with BSA were used for examining the influence of long-term antigenic stimulation on the galactosylation status of IgG and rheumatoid factor production. The results showed that the galactosylation profile of IgG varied during the humoral anti-BSA response in rabbits and that the accompanying RF response fluctuated in titer and binding avidity for differently galactosylated IgG. The immune complexes (IC) were found to be composed of differently galactosylated IgG differing in capacity to inhibit the agglutination activity of RF. Moreover, the ability of circulating RF to react avidly with rather small IC was associated with a lower content of galactose in complexed IgG. The results suggest that a certain dynamic relationship exists between the oligosaccharide moiety of IgG and the titer and avidity of RF during the normal anti-BSA response of rabbits.

Milosević-Jovcić N, Cirić D, Hajduković-Dragojlović L, Mircetić V. · Institute for Medical Research, Clinical Center of Serbia, Belgrade, Serbia and Montenegro. · Rheumatology (Oxford). · Pubmed #15238645 links to  free full text

Abstract: OBJECTIVE: To determine if there are the differences in titre and functional affinity for immunoglobulin (Ig) G subclasses and glycoforms between the Ga- and pan-specific IgM rheumatoid factors (RFs) present in the sera of patients with rheumatoid arthritis (RA), and to determine whether these two broad specificities have different functional roles in RA. METHODS: We used direct ELISA and modified ELISA to study the binding of IgM RF in the sera of 32 patients with RA with a range of RF titres to a panel of 14 IgG paraproteins of all four subclasses, some allotypes and different glycosylation patterns. RESULTS: Pan-specific RFs were mostly found in RA sera with high RF titres, and these RFs generally had higher avidity. A trend towards higher avidity of RFs with higher titre was observed for pan-specific, but not for Ga-specific RFs. With increasing titre, pan-specific RFs tended to react strongly with fucosylated and bisected variants of hypogalactosylated IgG3 of G3m(b1) allotype and hypergalactosylated IgG4 of 4a allotype. CONCLUSION: Among high-titred pan-specific IgM RFs, there is a subpopulation responsible for strong anti-IgG activity in RA. The possible mechanisms of production of pan- and Ga-specific RFs are discussed.