Skip to Main content Skip to Navigation
Journal articles

IgA-mediated human autoimmune hemolytic anemia as a result of hemagglutination in the spleen, but independent of complement activation and FcαRI

Abstract : Abstract Autoimmune hemolytic anemia (AIHA) due to warm-acting IgA autoantibodies is rare. We explored the pathogenic mechanisms underlying destruction of red blood cells (RBCs) in a patient with severe AIHA mediated exclusively by polymeric immunoglobulin A (pIgA) anti-Band 3 autoantibodies. The follow-up period was 17 months. RBCs were not destroyed by complement activation as no deposition of complement was observed on the patient's RBCs. pIgA eluted from the patient's RBCs did not induce RBC destruction through phagocytosis by monocytes or antibody–dependent cell–mediated cytotoxicity by natural killer cells. Induction of eryptosis (ie, RBC apoptosis) due to direct alteration of the RBC membrane by pIgA autoantibodies was also excluded. By contrast, upon incubation with pIgA-opsonized RBCs, substantial RBC membrane transfers (ie, trogocytosis) to monocytes were observed that might contribute to RBC immune destruction. This effect was poorly inhibited by blockers of Fc receptors, excluding a major contribution of FcαRI to this process. Histologic analysis revealed a massive accumulation of agglutinated RBCs with little sign of erythrophagocytosis in the spleen. These results, together with the efficacy of splenectomy 17 months after AIHA onset, suggest that the trapping and subsequent sequestration of agglutinated RBCs in the spleen are the principal pathogenic mechanisms of pIgA-mediated AIHA.
Complete list of metadata

https://www.hal.inserm.fr/inserm-03241603
Contributor : Philippe Chadebech <>
Submitted on : Friday, May 28, 2021 - 5:44:27 PM
Last modification on : Thursday, September 16, 2021 - 10:44:08 AM
Long-term archiving on: : Sunday, August 29, 2021 - 7:45:10 PM

File

 Restricted access
To satisfy the distribution rights of the publisher, the document is embargoed until : jamais

Please log in to resquest access to the document

Identifiers

Citation

Philippe Chadebech, Marc Michel, Daniel Janvier, Kazunori Yamada, Christiane Copie-Bergman, et al.. IgA-mediated human autoimmune hemolytic anemia as a result of hemagglutination in the spleen, but independent of complement activation and FcαRI. Blood, American Society of Hematology, 2010, 116 (20), pp.4141-4147. ⟨10.1182/blood-2010-03-276162⟩. ⟨inserm-03241603⟩

Share

Metrics

Record views

25