The effect of anti-CD40 ligand antibody on B cells in human systemic lupus erythematosus

Arthritis Rheum. 2002 Jun;46(6):1554-62. doi: 10.1002/art.10273.


Objective: To determine the immunologic effects of anti-CD40 ligand (anti-CD40L) therapy in 5 patients with systemic lupus erythematosus nephritis who participated in an open-label study of a humanized anti-CD40L monoclonal antibody.

Methods: Serum and peripheral blood mononuclear cells were obtained before, during, and after treatment, and the frequency of Ig and anti-DNA antibody-secreting B cells was analyzed by enzyme-linked immunospot assay and by analysis of Epstein-Barr virus (EBV)-transformed B cell lines. To determine the effect of treatment on somatic mutation of Ig genes, reverse transcriptase-polymerase chain reaction was performed on messenger RNA from 4 patients, using primers specific for the DP-47 heavy chain gene and for IgG. Finally, B cell phenotype was investigated using flow cytometry.

Results: Even a brief period of treatment with anti-CD40L markedly reduced the frequency of IgG and IgG anti-DNA antibody-producing B cells, and these changes persisted for several months after cessation of treatment. To confirm these findings, EBV-transformed B cell lines were screened from each of 3 patients, and a 10-fold decrease in anti-DNA antibody-secreting cell lines was found after treatment in all 3 patients. Few differences in mutation patterns were observed before and after treatment; however, the frequency of germline-encoded DP-47 sequences was significantly increased before treatment and normalized following treatment. Flow cytometric analysis of B cells revealed expansion of a CD27-/IgD- B cell subset in some of the patients, which did not change with treatment.

Conclusion: These are the first mechanistic studies of the effect of anti-CD40L therapy in human autoimmune disease. The results suggest that further studies of CD40L blockade are warranted.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Antibodies, Antinuclear / genetics
  • Antibodies, Antinuclear / immunology
  • Antibodies, Monoclonal / pharmacology*
  • B-Lymphocytes / immunology*
  • Biomarkers
  • CD40 Ligand / immunology*
  • Cell Line, Transformed
  • Female
  • Flow Cytometry
  • Herpesvirus 4, Human / genetics
  • Humans
  • Immunoenzyme Techniques
  • Immunoglobulin G / genetics
  • Immunoglobulin G / immunology
  • In Vitro Techniques
  • Lupus Nephritis / immunology*
  • Lupus Nephritis / therapy*
  • Male
  • Mutation / immunology
  • RNA, Messenger / analysis


  • Antibodies, Antinuclear
  • Antibodies, Monoclonal
  • Biomarkers
  • Immunoglobulin G
  • RNA, Messenger
  • CD40 Ligand