Platelet‐associated immunoglobulins IgG, IgM, IgA and complement C3 in immune and nonimmune thrombocytopenic disorders

Abstract

A two-stage radioactive antiglobulin test--using unlabelled antisera specific for IgG, IgA, IgM and C3 followed by binding of 125I-staphylococcal protein A--was applied to determine platelet-associated immunoglobulins (PAIg) and complement (PAC3) in thrombocytopenias of various etiologies. One hundred and one patients with immune thrombocytopenia (chronic autoimmune, 48; acute autoimmune, 37; Evans syndrome, nine; connective tissue diseases, seven) and 20 patients with presumed nonimmune thrombocytopenia (bone marrow aplasia or malignancy, six; septicemia, five; hypersplenism, five; cirrhosis of liver, three; others, one) were studied. Increased levels of PAIg/C3 were found in 76% of patients with immune thrombocytopenia. PAIgG was raised in 66%, PAIgM in 57%, PAIgA in 44%, and PAC3 in 29%. Isolated elevation of PAIgG and of PAIgM was found in four and three cases, respectively; PAIgA and PAC3 were elevated in one case each. PAIgG was associated with PAIgM in 56%, with PAIgA in 34%, and with PAC3 in 27%. Both patients with Evans' syndrome and patients with connective tissue diseases had significantly higher PAIgM levels than the other patients with immune thrombocytopenia. In patients with nonimmune thrombocytopenia, increased rates of PAIg/C3 were also encountered. Positive test results were found in 88% (PAIgG 88%, PAIgM 47%, PAIgA 35%, and PAC3 24%). In immune-mediated thrombocytopenia, we observed a significant inverse correlation between platelet counts and PAIgG, PAIgA, and PAC3, but not with PAIgM. In contrast, no such correlation was found in patients with nonimmune thrombocytopenia. Our data indicate that the evaluation of neither parameter alone nor the combination of PAIg/C3 will discriminate between immune and nonimmune thrombocytopenia. Preferential coating with certain immunoglobulins, however, may be present in some subgroups of immune thrombocytopenias.

Prospective evaluation of a new platelet glycoprotein (GP)-specific assay (PakAuto) in the diagnosis of autoimmune thrombocytopenia (AITP)

“…Kelton et al [9] compared four different types of Phase II assays prospectively in patients in whom TP was caused by both immune and nonimmune conditions and showed that, while highly sensitive, these assays lacked sufficient specificity to be clinically useful. The findings in other studies were similar, showing an overall sensitivity of 76-91%, and specificity of 12-27%, for Phase II assays [10][11][12].…”

Idiopathic autoimmune thrombocytopenia: Evidence for redistribution of platelet antibodies into the circulation after immunoadsorption treatment

“…A positive correlation between P-selectin-positive platelets and PAIgG was demonstrated previously, suggesting that activated platelets bind more antibodies than non-activated platelets [10]. Levels of PAIgG are inversely correlated with platelet counts [11,12]. We therefore assume that our cases with severe thrombocytopenia had high PAIgG levels.…”

Complement activation on platelets: Implications for vascular inflammation and thrombosis

“…Both humoral and cell mediated mechanisms have been described, but the role of the complement system has not been well defined (McMillan 2000). Limited studies of plasma complement deficiencies in patients with ITP (Trent et al, 1980; Ohali et al, 2005) and elevated levels of platelet associated complement, particularly C3 (Kayser et al, 1983; Foster et al, 1989; Panzer et al, 1986) have been reported. The observed association between platelet associated IgG/IgM and C3 suggests the potential for classical pathway complement activation on the platelet surface.…”