IgA-mediated human autoimmune hemolytic anemia as a result of hemagglutination in the spleen, but independent of complement activation and FcαRI.
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.
Chadebech
Philippe
P
Etablissement Français du Sang, Ile de France, Henri Mondor Hospital, Créteil, France.
Michel
Marc
M
Janvier
Daniel
D
Yamada
Kazunori
K
Copie-Bergman
Christiane
C
Bodivit
Gwellaouen
G
Bensussan
Armand
A
Fournie
Jean-Jacques
JJ
Godeau
Bertrand
B
Bierling
Philippe
P
Izui
Shozo
S
Noizat-Pirenne
France
F
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*
D015703:Antigens, CD; D001323:Autoantibodies; C036832:Fc(alpha) receptor; D007070:Immunoglobulin A; D011961:Receptors, Fc