title: IgA-mediated human autoimmune hemolytic anemia as a result of hemagglutination in the spleen, but independent of complement activation and FcαRI.
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.
authors.affiliation: Etablissement Français du Sang, Ile de France, Henri Mondor Hospital, Créteil, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Chadebech
authors.forename: Marc
authors.initials: M
authors.lastname: Michel
authors.forename: Daniel
authors.initials: D
authors.lastname: Janvier
authors.forename: Kazunori
authors.initials: K
authors.lastname: Yamada
authors.forename: Christiane
authors.initials: C
authors.lastname: Copie-Bergman
authors.forename: Gwellaouen
authors.initials: G
authors.lastname: Bodivit
authors.forename: Armand
authors.initials: A
authors.lastname: Bensussan
authors.forename: Jean-Jacques
authors.initials: JJ
authors.lastname: Fournie
authors.forename: Bertrand
authors.initials: B
authors.lastname: Godeau
authors.forename: Philippe
authors.initials: P
authors.lastname: Bierling
authors.forename: Shozo
authors.initials: S
authors.lastname: Izui
authors.forename: France
authors.initials: F
authors.lastname: Noizat-Pirenne
mesh_terms: D000328:Adult; D000744:Anemia, Hemolytic, Autoimmune / Q000276:immunology* / Q000473:pathology; D000920:Antibody-Dependent Cell Cytotoxicity / Q000276:immunology; D015703:Antigens, CD / Q000276:immunology*; D017209:Apoptosis; D001323:Autoantibodies / Q000276:immunology; D003167:Complement Activation / Q000276:immunology*; D004912:Erythrocytes / Q000276:immunology / Q000473:pathology; D005260:Female; D006384:Hemagglutination / Q000276:immunology*; D006801:Humans; D007070:Immunoglobulin A / Q000276:immunology*; D016131:Lymphocyte Subsets / Q000276:immunology; D009000:Monocytes / Q000166:cytology / Q000276:immunology; D010587:Phagocytosis / Q000276:immunology; D011961:Receptors, Fc / Q000276:immunology*; D013154:Spleen / Q000276:immunology*
chemical_list: D015703:Antigens, CD; D001323:Autoantibodies; C036832:Fc(alpha) receptor; D007070:Immunoglobulin A; D011961:Receptors, Fc