Immunological tolerance loss vs. erythrocyte self antigens and cytokine network disregulation in autoimmune hemolytic anaemia.
Recent studies on animal and human autoimmune hemolytic anaemia (AIHA) suggest that the loss of immunological tolerance vs. erythrocyte (Er) self antigens (Ag) may be primed by different mechanisms: ignorance of Er self Ag, molecular mimicry between self and non-self Ag, polyclonal T and/or B cells activation, errors in central or peripheral tolerance, immunoregulatory disturbances including the alteration of cytokines network. In vitro stimulation by synthetic Rh peptides indicates that ignorant T and/or B cells from patients with AIHA may recognize criptic Er self Ag. The AIHA associated with bacterial or viral infections seems to be produced by polyclonal T and/or B cell activation against foreign Ag that mimics protein or carbohydrate epitopes on Er. Polyclonal activation of host B cell clones by donor T cells causes the AIHA in chronic graft-versus-host disease. Mouse lines expressing a transgene with autoantibody (autoAb) activity against murine Er have shown that non-deleted peripheral B cell clones may produce Er autoAb. In human a genetic defect of Fas/FasL autoreactive lymphocyte apoptosis may be associated with AIHA. Th1/Th2 cytokines or IL10/IL12 imbalance may induce AIHA: in NZB mice and in human AIHA there is an increased production of Th2 cytokines such as IL4 and IL10 but INF-gamma and IL12 reduced production. Particularly, IL10 seems to act as critical mediator for the Er autoAb production.
Immunohematology and Blood Transfusion Unit, Catholic University 'Sacro Cuore', Rome, Italy. n.gattavilla@tiscali.it
Enzo
E
Fagiolo
D000743:Anemia, Hemolytic / Q000209:etiology / Q000276:immunology* / Q000378:metabolism; D000818:Animals; D001324:Autoantigens / Q000276:immunology; D001327:Autoimmune Diseases / Q000209:etiology / Q000276:immunology* / Q000378:metabolism; D001402:B-Lymphocytes / Q000276:immunology; D016207:Cytokines / Q000378:metabolism*; D004912:Erythrocytes / Q000276:immunology*; D006801:Humans; D007108:Immune Tolerance / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology
D001324:Autoantigens; D016207:Cytokines