Involvement of Fcα/μ Receptor in IgM Anti-Platelet, but Not Anti–Red Blood Cell Autoantibody Pathogenicity in Mice

Abstract

IgM anti-mouse platelet autoantibodies cause thrombocytopenia by mediating uptake of opsonized thrombocytes, whereas IgM anti-erythrocyte autoantibodies induce anemia through a phagocytosis-independent cell destruction. In this article, we show that infection with lactate dehydrogenase–elevating virus, a benign mouse arterivirus, exacerbates the pathogenicity of IgM anti-platelet, but not anti-erythrocyte autoantibodies. To define the role of Fcα/μ receptor (Fcα/μR) in IgM-mediated thrombocytopenia and anemia, we generated mice deficient for this receptor. These animals were resistant to IgM autoantibody-mediated thrombocytopenia, but not anemia. However, the lactate dehydrogenase–elevating virus–induced exacerbation of thrombocytopenia was not associated with enhanced Fcα/μR expression on macrophages. These results indicate that Fcα/μR is required for the pathogenicity of IgM anti-platelet autoantibodies but is not sufficient to explain the full extent of the disease in virally infected animals.

Cytomegalovirus-Associated Hemolytic Anemia in an Infant Born to a Mother with Lupus

“…The primary infection and reactivation of CMV could be a trigger at the onset of both bone marrow failure and autoimmune cytopenia with or without underlying disease [3, 5]. In the present case, nonvertical infection might appear to activate macrophages or dendritic cells through the production of type-1 and type-2 interferon, which promoted the phagocytic activity and antigen presentation of these cells, resulting in the augmented destruction of circulating hematopoietic cells [6, 7]. Moreover, endogenous anti-CMV IgG antibodies have been reported to be directed at a non-D portion of the Rh complex, suggesting a pathogenic role of anti-CMV IgG as the anti-erythrocyte antibody leading to postinfectious acute hemolysis [8].…”

Diagnostic and Predictive Contribution of Autoantibodies Screening in a Large Series of Patients With Primary Immunodeficiencies

“…Unlike IgM anti-erythrocyte autoantibody that promotes anemia through a massive agglutination of RBCs in spleen and liver, PA-IgM induces thrombocytopenia through uptake of opsonized platelets ( 19 , 20 ). In the mouse, it has been reported that IgM autoantibody-mediated thrombocytopenia was macrophage dependent and the Fcα/μR was required for macrophage uptake of opsonized thrombocytes ( 21 ). Complement fixation on IgM might also potentially activate phagocytosis involving complement receptors expressed on macrophages ( 16 ).…”