Anti-CD20 Antibody Prevents Red Blood Cell Alloimmunization in a Mouse Model

J Immunol. 2017 Dec 1;199(11):3771-3780. doi: 10.4049/jimmunol.1700754. Epub 2017 Oct 20.

Abstract

Alloimmunization against RBCs can cause life-threatening delayed hemolytic transfusion reactions. Anti-CD20 Ab has recently been used to prevent alloimmunization. However, its effects remain unclear, particularly in lymphoid organs. We investigated the impact of murine anti-CD20 Ab in the blood and spleen. We assessed protocols for preventing primary alloimmunization and for abolishing established alloimmunization. Prophylactic protocols prevented alloimmunization. However, anti-CD20 treatment could only limit the further amplification of established alloimmunization. Residual B cell subtype distribution was disrupted in the spleen, but adoptive transfer studies indicated that these cells were neither plasma nor memory cells. Anti-CD20 Ab had a major effect on alloreactive CD4+ T cells, increasing the expansion of this population and its CD40 expression, while lowering its CD134 expression, thereby confirming its role in alloimmunization. In conclusion, this study shows that anti-CD20 immunotherapy can prevent RBC Ab development. However, this immunotherapy is limited by the increase in alloreactive CD4+ T lymphocytes. Nevertheless, treatment with anti-CD20 Abs should be considered for patients requiring transfusion with a very high risk of alloimmunization and life-threatening complications.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Monoclonal / administration & dosage*
  • Antibody Formation
  • Antigens, CD20 / immunology
  • B-Lymphocytes / immunology*
  • Blood Transfusion*
  • CD4-Positive T-Lymphocytes / immunology*
  • Cell Proliferation
  • Cells, Cultured
  • Erythrocytes / immunology*
  • Hemolysis
  • Humans
  • Immunization
  • Immunotherapy / methods*
  • Isoantigens / immunology
  • Mice
  • Mice, Inbred Strains
  • Mice, Transgenic
  • Risk
  • Transfusion Reaction / immunology
  • Transfusion Reaction / therapy*

Substances

  • Antibodies, Monoclonal
  • Antigens, CD20
  • Isoantigens