The role of complement regulatory proteins (CD55 and CD59) in the pathogenesis of autoimmune hemocytopenias.
Mammalian cells are provided with surface-bound complement regulatory proteins that protect them from uncontrolled complement-mediated lysis. Two of these regulators in humans, CD55 and CD59, are glycosylphosphatidylinositol-anchored, type I cell surface proteins, which inhibit formation of the C3 convertases and prevent the terminal polymerization of the membrane attack complex, respectively. Paroxysmal nocturnal hemoglobinuria is a genetic disorder due to the impaired conformation of the glycosylphosphatidylinositol-anchor, that results in the deficient expression of CD55 and CD50 which leads to excessive destruction of red cells and leukocytes. We have studied the expression of these two molecules in patients with autoimmune hemolytic anemia, autoimmune thrombocytopenia, and patients with systemic lupus erythematosus showing lymphopenia, and found that all three types of cytopenias are associated to deficient expression of CD55 and CD59 on the involved hematopoietic lineage. These are the first descriptions of acquired deficiencies of complement regulatory molecules in human disease, and it seems, from our results, that such deficiencies might play a pathogenic role in the mechanism of cell destruction. Although autoantibodies appeal as the best candidates to cause underexpression of CD55 and CD59, the search for an association to the presence and titers of most frequent self-reactive antibodies has proved non-existent.
Ruiz-Argüelles
Alejandro
A
Department of Immunology, Laboratorios Clínicos de Puebla, Diaz Ordaz 808, Puebla, PUE 72530, Mexico. aruiz@clinicaruiz.com <aruiz@clinicaruiz.com>
Llorente
Luis
L
D000744:Anemia, Hemolytic, Autoimmune / Q000097:blood / Q000209:etiology* / Q000276:immunology*; D018958:CD55 Antigens / Q000276:immunology*; D018957:CD59 Antigens / Q000276:immunology*; D006801:Humans; D008231:Lymphopenia / Q000097:blood / Q000209:etiology* / Q000276:immunology; D016553:Purpura, Thrombocytopenic, Idiopathic / Q000097:blood / Q000209:etiology* / Q000276:immunology
D018958:CD55 Antigens; D018957:CD59 Antigens