Exacerbation of autoantibody-mediated thrombocytopenic purpura by infection with mouse viruses.
Antigenic mimicry has been proposed as a major mechanism by which viruses could trigger the development of immune thrombocytopenic purpura (ITP). However, because antigenic mimicry implies epitope similarities between viral and self antigens, it is difficult to understand how widely different viruses can be involved by this sole mechanism in the pathogenesis of ITP. Here, we report that in mice treated with antiplatelet antibodies at a dose insufficient to induce clinical disease by themselves, infection with lactate dehydrogenase-elevating virus (LDV) was followed by severe thrombocytopenia and by the appearance of petechiae similar to those observed in patients with ITP. A similar exacerbation of antiplatelet-mediated thrombocytopenia was induced by mouse hepatitis virus. This enhancement of antiplatelet antibody pathogenicity by LDV was not observed with F(ab')2 fragments, suggesting that phagocytosis was involved in platelet destruction. Treatment of mice with clodronate-containing liposomes and with total immunoglobulin G (IgG) indicated that platelets were cleared by macrophages. The increase of thrombocytopenia triggered by LDV after administration of antiplatelet antibodies was largely suppressed in animals deficient for gamma-interferon receptor. Together, these results suggest that viruses may exacerbate autoantibody-mediated ITP by activating macrophages through gamma-interferon production, a mechanism that may account for the pathogenic similarities of multiple infectious agents.
Musaji
Andrei
A
Unit of Experimental Medicine, Institute for Cellular Pathology, Université Catholique de Louvain, Brussels, Belgium.
Cormont
Françoise
F
Thirion
Gaëtan
G
Cambiaso
César L
CL
Coutelier
Jean-Paul
JP
D000818:Animals; D000906:Antibodies / Q000737:chemistry; D000911:Antibodies, Monoclonal / Q000737:chemistry; D001323:Autoantibodies; D001327:Autoimmune Diseases / Q000821:virology; D001792:Blood Platelets / Q000276:immunology* / Q000378:metabolism; D007128:Immunoglobulin Fragments; D007074:Immunoglobulin G / Q000737:chemistry; D007371:Interferon-gamma / Q000378:metabolism; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D007772:Lactate dehydrogenase-elevating virus / Q000378:metabolism*; D008081:Liposomes / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008808:Mice, Inbred CBA; D008819:Mice, Nude; D010587:Phagocytosis; D010976:Platelet Count; D016553:Purpura, Thrombocytopenic, Idiopathic / Q000276:immunology* / Q000821:virology*; D013154:Spleen / Q000166:cytology
D000906:Antibodies; D000911:Antibodies, Monoclonal; D001323:Autoantibodies; D007128:Immunoglobulin Fragments; D007074:Immunoglobulin G; D008081:Liposomes; D007371:Interferon-gamma; D007770:L-Lactate Dehydrogenase