Serologic changes following B lymphocyte depletion therapy for rheumatoid arthritis

Abstract

Objective. To explore the changes in serologic variables and clinical disease activity following B lymphocyte depletion in 22 patients with rheumatoid arthritis (RA).Methods. B lymphocyte depletion was attained using combination therapy based on the monoclonal anti-CD20 antibody rituximab. Levels of a serologic indicator of inflammation, C-reactive protein (CRP), of antimicrobial antibodies, of autoantibodies including IgA-, IgM-, and IgG-class rheumatoid factors (RF), and of antibodies to cyclic citrullinated peptide (anti-CCP) were assayed.Results. The majority of patients showed a marked clinical improvement after treatment with rituximab, with benefit lasting up to 33 months. Levels of total serum immunoglobulins fell, although the mean values each remained within the normal range. Whereas the IgM-RF response paralleled the changes in total serum IgM levels, the levels of IgA-RF, IgG-RF, and IgG and anti-CCP antibodies decreased significantly more than did those of their corresponding total serum immunoglobulin classes. The kinetics for the reduction in CRP levels also paralleled the decreases in autoantibody levels. In contrast, levels of antimicrobial antibodies did not change significantly. B lymphocyte return occurred up to 21 months posttreatment. The time to relapse after B lymphocyte return was often long and unpredictable (range 0-17 months). Relapse was, however, closely correlated with rises in the level of at least one autoantibody. Increased autoantibody levels were rarely observed in the absence of clinical change.Conclusion. Following B lymphocyte depletion in patients with RA, a positive clinical response occurred in correlation with a significant drop in the levels of CRP and autoantibodies. Antibacterial antibody levels were relatively well maintained. B lymphocyte return preceded relapse in all patients. There was also a temporal relationship between clinical relapse and rises in autoantibody levels. Although these observations are consistent with a role for B lymphocytes in the pathogenesis of RA, the precise mechanisms involved remain unclear.

Rituximab in relapsing Graves' disease, a phase II study

“…Apparently, no clear relation exists between the degree of depletion of MS4A1 positive cells from peripheral blood and the therapeutic effect. The relation between circulating levels of MS4A1 positive lymphocytes, serological markers of autoimmune disease and effectiveness of rituximab in autoimmune disease is complex, but a number of studies suggest an inverse relationship between proportions of B-cells, autoantibody titres and therapeutic effect in rheumatoid arthritis and lupus (10,17,26,27). In our study, the proportion of CD-20 positive lymphocytes was not associated with TBII levels.…”

Marginal zone B cells are naturally reactive to collagen type II and are involved in the initiation of the immune response in collagen-induced arthritis

“…6 This is also evident in rheumatoid arthritis, where B-cell depletion therapy contributes to a positive clinical response in correlation with a significant drop in auto-Abs. 7 Importantly, low levels of auto-Abs can be detected in the serum many years before clinical symptoms of rheumatoid arthritis, 8 suggesting that an early break in B-cell tolerance is underlying the disease.…”

MS and clinically isolated syndromes: Shared specificity but diverging clonal patterns of virus‐specific IgG antibodies produced in vivo and by CSF B cells in vitro

“…Of interest, a single case report on an SPS patient demonstrated a rapid decline of intrathecal GAD65 IgG antibodies following anti-CD20 treatment, which suggested a successful targeting and elimination of autoantibody producing B cells within the CNS (Baker 2005). Furthermore, clinical trials with B cell depletion in other autoimmune diseases, such as RA and SLE, reported that certain autoantibodies, anti-DNA and rheumatoid factor, decayed after anti-CD20 B cell therapy (Cambridge 2003;Sfikakis 2005;. It is tempting to speculate that the continuously produced GAD65 IgG antibodies in SPS patients are being generated rapidly from renewing CD20 + B cell precursors, most consistent with the short-lived plasmablasts pathway.…”