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

Jennifer H. Anolik, Debbie Campbell, Raymond E. Felgar, Faith Young, Inaki Sanz, Joseph Rosenblatt, R. John Looney

Research output: Contribution to journalArticle

375 Scopus citations


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 FcγRIIa and FcγRIIIa 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/μl) to 16% (∼30 cells/μl) of the total peripheral blood lymphocytes. At 2 months posttreatment, B cell percentages were highly correlated with both the serum rituximab level and the FcγRIIIa genotype (R2 = 0.75, P = 0.002). The FcγRIIIa 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 rituximab in the treatment of autoimmune disease and indicate that Fc receptors are an important determinant of that variability. The findings further suggest the importance of antibody-dependent cell-mediated cytotoxicity and/or apoptosis induction via FcγRIIIa-expressing effector cells in the mechanism of B cell depletion by this widely used monoclonal antibody.

Original languageEnglish (US)
Pages (from-to)455-459
Number of pages5
JournalArthritis and rheumatism
Issue number2
StatePublished - Feb 1 2003


ASJC Scopus subject areas

  • Immunology and Allergy
  • Rheumatology
  • Immunology
  • Pharmacology (medical)

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