The relationship of FcγRIIIa genotype to degree of B cell depletion by rituximab in the treatment of systemic lupus erythematosus

作者：Jennifer H. Anolik, Debbie Campbell, Raymond E. Felgar, Faith M Young, Iñaki Sanz, Joseph D. Rosenblatt, Richard John Looney · 发表于：Arthritis & Rheumatism · 年份：2003 · DOI：10.1002/art.10764 · 被引用次数：427 · 研究领域：Monoclonal and Polyclonal Antibodies Research、Systemic Lupus Erythematosus Research、Biosimilars and Bioanalytical Methods

OBJECTIVE: Despite wide use of the anti-CD20 monoclonal antibody rituximab in the treatment of B cell lymphomas, the mechanism by which it causes B cell depletion remains a subject of controversy. As part of an ongoing phase I/II trial of rituximab in the treatment of systemic lupus erythematosus (SLE), we sought to determine whether the effectiveness of B cell depletion was influenced by polymorphisms of Fc receptors (FcR) on effector cells. METHODS: During rituximab treatment of 12 SLE patients, B cell depletion was monitored as a function of the serum rituximab level and FcgammaRIIa and FcgammaRIIIa genotypes at baseline and at 1 month and 2 months after treatment. FcR genotypes were determined by polymerase chain reaction. Serum levels of rituximab were measured by enzyme-linked immunosorbent assay (ELISA). B lymphocyte percentages were assessed by flow cytometry. RESULTS: B cell depletion was highly variable in this patient cohort, with B cell percentages at the 1-2-month posttreatment nadir ranging from undetectable (<0.1 cell/microl) to 16% ( approximately 30 cells/microl) of the total peripheral blood lymphocytes. At 2 months posttreatment, B cell percentages were highly correlated with both the serum rituximab level and the FcgammaRIIIa genotype (R(2) = 0.75, P = 0.002). The FcgammaRIIIa genotype was a significant independent predictor of the efficacy of B cell depletion (P = 0.019). CONCLUSION: These results highlight the potential variability of B cell depletion by...