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

Chadebech, Philippe
Michel, Marc
Janvier, Daniel
Yamada, Kazunori
Copie-Bergman, Christiane
Bodivit, Gwellaouen
Bensussan, Armand
Fournie, Jean-Jacques
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Published in Blood. 2010, vol. 116, no. 20, p. 4141-4147
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 FcalphaRI 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.
Keywords AdultAnemia, Hemolytic, Autoimmune/*immunology/pathologyAntibody-Dependent Cell Cytotoxicity/immunologyAntigens, CD/*immunologyApoptosisAutoantibodies/immunologyComplement Activation/*immunologyErythrocytes/immunology/pathologyFemaleHemagglutination/*immunologyHumansImmunoglobulin A/*immunologyLymphocyte Subsets/immunologyMonocytes/cytology/immunologyPhagocytosis/immunologyReceptors, Fc/*immunologySpleen/*immunology
PMID: 20644119
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Research group Lupus érythémateux systémique, de l'anémie hémolytique et de la glomérulonéphrite (168)
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CHADEBECH, Philippe et al. IgA-mediated human autoimmune hemolytic anemia as a result of hemagglutination in the spleen, but independent of complement activation and FcalphaRI. In: Blood, 2010, vol. 116, n° 20, p. 4141-4147. doi: 10.1182/blood-2010-03-276162 https://archive-ouverte.unige.ch/unige:20835

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Deposited on : 2012-05-23

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