Mechanisms of immunological tolerance loss versus erythrocyte self-antigens and autoimmune hemolytic anemia.
Recent studies on animal and human autoimmune hemolytic anemia (AIHA) suggest that immunological tolerance loss toward red blood cells (RBC) self-antigens may be originate by different, non-mutually exclusive, mechanisms. According to now available data the identified mechanisms may be: ignorance against RBC self-antigens; molecular mimicry; polyclonal T and/or B cells activation; errors in central or peripheral tolerance; immunoregulatory disorders including cytokine network alteration. In some patients with AIHA, stimulation of PMBC by synthetic Rh peptides indicate that ignorant T and/or B cell clones may recognize cryptic RBC self-antigens. AIHA associated with bacterial or viral infections seems to be produced by polyclonal T and/or B cells activation against foreign antigens which mimic protein or carbohydrate epitopes on RBC. Polyclonal activation of host B cell clones by donor alloreactive T cells causes the AIHA in chronic GVHD. As the tolerance loss is concerned, experiments on mouse lines expressing a transgene with autoantibody activity against murine RBC have shown that non-deleted peripheral B cell clones may produce RBC autoantibodies. In humans a genetic defect of Fas/FasL autoreactive lymphocytes apoptosis may be associated to AIHA. Immunoregulatory disorders due to depletion of CD4+ CD25+ T cells or Th1/Th2 cytokines imbalance may induce autoimmune diseases. In mice AIHA may be induced or improved by cytokines or anticytokine antibodies administration. In NZB/W mice and human AIHA there is an increased production of Th2 cytokines as IL4 and IL10 but INF-gamma reduced production. In addition in human AIHA has been shown a downregulation of IL12 and therefore, an IL10/IL12 immunoregulatory circuit imbalance which might facilitate the RBC autoantibodies production.
Fagiolo
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E
Laboratory of Immunohematology, Catholic University of Sacro Cuore, Rome, Italy.
Toriani-Terenzi
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C
D000744:Anemia, Hemolytic, Autoimmune / Q000209:etiology*; D000818:Animals; D001324:Autoantigens / Q000276:immunology*; D015551:Autoimmunity / Q000276:immunology; D004912:Erythrocytes / Q000276:immunology*; D006801:Humans; D007108:Immune Tolerance / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D008814:Mice, Inbred NZB; D018716:Molecular Mimicry / Q000276:immunology
D001324:Autoantigens