Anti-CD20 antibody therapy and susceptibility to Pneumocystis pneumonia.

Abstract

Anti-CD20 antibody therapy has been a useful medication for managing non-Hodgkin's lymphoma as well as autoimmune diseases characterized by autoantibody generation. CD20 is expressed during most developmental stages of B lymphocytes; thus, CD20 depletion leads to B-lymphocyte deficiency. As the drug has become more widely used, there has been an increase in the number of case reports of patients developing Pneumocystis pneumonia. The role of anti-CD20 in Pneumocystis jirovecii infection is under debate due to the fact that most patients receiving it are on a regimen of multiple immunosuppressive medications. To address the specific role of CD20 depletion in host immunity against Pneumocystis, we examined a murine anti-CD20 depleting antibody. We demonstrated that anti-CD20 alone is permissive for Pneumocystis infection and that anti-CD20 impairs components of type II immunity, such as production of interleukin-4 (IL-4), IL-5, and IL-13 by whole-lung cells, in response to Pneumocystis murina. We also demonstrated that CD4(+) T cells from mice treated with anti-CD20 during Pneumocystis infection are incapable of mounting a protective immune response when transferred into Rag1(-/-) mice. Thus, CD20(+) cells are critical for generating protective CD4(+) T-cell immune responses against this organism.

• Authors: Waleed Elsegeiny, Taylor Eddens, Kong Chen, Jay K Kolls
• Journal: Infection and immunity (Infect Immun) Vol. 83 Issue 5 Pg. 2043-52 (May 2015) ISSN: 1098-5522 [Electronic] United States
• PMID: 25733518 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
• Copyright: Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Chemical References

• Immunologic Factors
• Rituximab

Topics

• Animals
• CD4-Positive T-Lymphocytes (drug effects, immunology)
• Disease Models, Animal
• Disease Susceptibility
• Immunologic Factors (adverse effects, therapeutic use)
• Mice, Inbred C57BL
• Pneumocystis (immunology)
• Pneumonia, Pneumocystis (chemically induced, immunology)
• Rituximab (adverse effects, therapeutic use)