IgG and IgM Rheumatoid Factors in Rheumatoid Arthritis

Abstract

Penicillamine treatment of patients with rheumatoid arthritis (RA) leads to falling titers of agglutinating IgM rheumatoid factor (RF), but its effect on IgG RF has not been described. Using specific solid phase radioimmunoassays, we have determined serial levels of IgM RF and IgG RF in 18 patients receiving penicillamine for 1 year, and correlated the results with the change in RA activity. Mean IgM RF levels fell to 76 f 10% (mean & SEM) after 3 months, and 30 k 5% of the pretreatment value after 1 year of penicillamine treatment. This decline was greater than that for total IgM (P < O.OOOl), indicating a selective reduction of RF. Patients receiving maintenance doses of 750 mg/day manifested more rapid and greater decreases than did those given 250 mglday.In contrast, serial mean IgG RF levels did not change significantly, and actually increased in 6 of 18 cases. At onset, there was a significant correlation with erythrocyte sedimentation rate for both IgM RF (r = 0.535, P = 0.05) and IgG RF levels (r = 0.570, P = 0.02).

Predictive Value of Antibodies to Citrullinated Peptides and Rheumatoid Factors in Anti‐TNF‐α Treated Patients

“…A reduction of IgM RF, IgG RF, and IgA RF levels after 1 year of methotrexate treatment was also reported by Spadaro and co‐workers 22 . Other studies have evaluated the effect of penicillamine, gold salts, minocycline, and sulphasalazine on RF levels showing that treatment can decrease the production of IgM RF and, to a lesser extent, of IgA RF and IgG RF 7,21–24 . Recently, Mikuls et al showed a good correlation between clinical response and a drop in IgM RF levels in 64 patients treated with different DMARDs for about 1 year 23 …”

Evidence for differential effects of sulphasalazine on systemic and mucosal immunity in rheumatoid arthritis.

“…However, more recent studies have shown that this RF isotype is also present and may be produced in nonmucosal compartments.25 70 71 Furthermore, evidence for local production of both IgAl RF and IgA2 RF subclasses in mucosal (saliva) and in non-mucosal (synovial fluid) compartments has been put forward, and a predominance of IgA2 RF production in salivary glands compared with synovial fluid was observed. 25 Reduction of RF has been demonstrated after treatment with SASP and other antirheumatic agents, for example D-penicillamine, gold, and methotrexate.3 53 55 [72][73][74][75][76] Because the changes in IgA RF and IgM RF did not correlate with the respective changes in serum immunoglobulin concentrations in the SASP treated patients (data not shown), the reductions in RF are not considered to be related to the changes in the overall production of immunoglobulins. Rather, it seems plausible that SASP directly inhibits RF production, an influence that is selective for IgA RF and IgM RF-committed B cells, as synthesis of IgG RF was not affected.…”

Inhibition of the covalent binding reaction of complement component C4 by penicillamine, an anti-rheumatic agent

“…Complement-derived activation fragments, particularly C5a (Wedmore & Williams, 1981), are likely to be important inflammatory mediators in rheumatoid arthritis (Moxley & Ruddy, 1987). D(-)-Penicillamine [D(-)-/fl,-dimethylcysteine] has been used as an anti-rheumatic agent, but its mechanism of action is not clearly established, although reduction of disulphide bridges in Rheumatoid Factor (Wernick et al, 1983) and inhibition of collagen cross-linking (Nimni et al, 1972) have been suggested. One major problem with penicillamine as an anti-rheumatic drug is that there is a high incidence of patients suffering adverse side effects, which include problems in clearance of immune complexes with resulting proteinuria and glomerulonephritis (Andrews et al, 1973;Davison et al, 1977;Kean et al, 1980).…”