Comparison of platelet immunity in patients with SLE and with ITP

Abstract

Idiopathic thrombocytopenic purpura (ITP) is characterized by the development of a speci®c anti-platelet autoantibody immune response mediating the development of thrombocytopenia. Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by the production of a wide variety of autoantibodies. In 15±20% of SLE cases, patients develop thrombocytopenia which appears to be autoimmune in nature (SLE-TP). To better understand the pathogenesis of the thrombocytopenia associated with SLE, we investigated the overlapping platelet and cellular immune features between SLE and ITP. Thirty-one patients with SLE, eight with SLE-TP, and 17 with ITP, were studied and compared to 60 healthy controls. We evaluated platelet-associated IgG, platelet microparticles, reticulated platelets, platelet HLA-DR expression, in vivo cytokine levels, lymphocyte proliferation, and the T lymphocyte anti-platelet immune response in these patients. Patients with SLE-TP and those with ITP had increased platelet-associated IgG, an increased percentage of platelet microparticles, a higher percentage of reticulated platelets and larger platelets, suggesting antibody-mediated platelet destruction and increased platelet production. More than 50% of patients with ITP had increased HLA-DR on their platelet surface whereas subjects with SLE-TP did not. Analysis of serum cytokines demonstrated increased levels of IL-10, IL-15 and TNF-a in patients with SLE, but in those with ITP, only increased levels of IL-15 were seen, no increases in any of these cytokines were observed in patients with in SLE-TP. The ability of lymphocytes to proliferate in response to phorbol myristate acetate (PMA) stimulation was increased in SLE-TP, but was normal in both SLE and ITP. Lymphocytes from subjects with ITP displayed an increased ability to proliferate on exposure to platelets, in contrast, those with SLE-TP did not. While the number of subjects evaluated with SLE-TP was small, these data reveal a number of dierences in the immunopathogenesis between SLE-TP and ITP. Ó

Copy number variation of the activating FCGR2C gene predisposes to idiopathic thrombocytopenic purpura

“…This may lead to increased platelet destruction in ITP, in which these cytokines are present in sera of patients. 44,45 In conclusion, we found that FCGR2C-ORF predisposes to ITP. We have shown that Fc␥RIIc is expressed by phagocytes and NK cells and that this enhances effector function toward antibodycoated targets.…”

Adult chronic idiopathic thrombocytopenic purpura (ITP) is the manifestation of a type-1 polarized immune response

“…Significantly reduced serum IL-10 levels have been found in ITP patients with active disease compared with clinically stable patients and healthy controls. 13 Conversely, raised serum IL-10 levels have been described in pediatric patients with chronic ITP, 10,15 whereas in another study 19 IL-10 levels were found to be similar between patients and controls.…”

Prevalence and clinical significance of elevated antinuclear antibody test in children and adult patients with idiopathic thrombocytopenic purpura

“…However, immune thrombocytopenia has been associated with autoimmune disorders such as autoimmune hemolytic anemia [4], SLE [5], and autoimmune thyroiditis [6]. Thrombocytopenia is the major hematological complication in patients with SLE.…”