title: Enhancement of autoantibody pathogenicity by viral infections in mouse models of anemia and thrombocytopenia.
abstract: Viral infections are involved in the pathogenesis of blood autoimmune diseases such as hemolytic anemia and thrombocytopenia. Although antigenic mimicry has been proposed as a major mechanism by which viruses could trigger the development of such diseases, it is not easy to understand how widely different viruses might induce these blood autoimmune diseases by this sole mechanism. In mice infected with lactate dehydrogenase-elevating virus (LDV), or mouse hepatitis virus, and treated with anti-erythrocyte or anti-platelet monoclonal autoantibodies at a dose insufficient to induce clinical disease by themselves, the infection sharply enhances the pathogenicity of autoantibodies, leading to severe anemia or thrombocytopenia. This effect is observed only with antibodies that induce disease through phagocytosis. Moreover, the phagocytic activity of macrophages from infected mice is increased and the enhancing effect of infection on autoantibody-mediated pathogenicity is strongly suppressed by treatment of mice with clodronate-containing liposomes. Finally, the disease induced by LDV after administration of autoantibodies is largely suppressed in animals deficient for gamma-interferon receptor. Together, these observations suggest that viruses may trigger autoantibody-mediated anemia or thrombocytopenia by activating macrophages through gamma-interferon production, a mechanism that may account for the pathogenic similarities of multiple infectious agents.
authors.affiliation: Unit of Experimental Medicine, Institute for Cellular and Molecular Pathology, Université catholique de Louvain, Av. Hippocrate 7430, B-1200 Bruxelles, Belgium.
authors.forename: Andrei
authors.initials: A
authors.lastname: Musaji
authors.forename: Mory
authors.initials: M
authors.lastname: Meite
authors.forename: Laurent
authors.initials: L
authors.lastname: Detalle
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Franquin
authors.forename: Françoise
authors.initials: F
authors.lastname: Cormont
authors.forename: Véronique
authors.initials: V
authors.lastname: Préat
authors.forename: Shozo
authors.initials: S
authors.lastname: Izui
authors.forename: Jean-Paul
authors.initials: JP
authors.lastname: Coutelier
mesh_terms: D000744:Anemia, Hemolytic, Autoimmune / Q000276:immunology* / Q000821:virology*; D000818:Animals; D001323:Autoantibodies / Q000633:toxicity*; D004195:Disease Models, Animal; D007772:Lactate dehydrogenase-elevating virus / Q000472:pathogenicity; D008264:Macrophages / Q000276:immunology; D051379:Mice; D010587:Phagocytosis / Q000276:immunology; D016553:Purpura, Thrombocytopenic, Idiopathic / Q000276:immunology* / Q000821:virology*; D014777:Virus Diseases / Q000150:complications*
chemical_list: D001323:Autoantibodies