|کد مقاله||کد نشریه||سال انتشار||مقاله انگلیسی||ترجمه فارسی||نسخه تمام متن|
|5666290||1407794||2017||7 صفحه PDF||سفارش دهید||دانلود کنید|
Homozygote genotype V247 of the Î²2-glycoprotein-I (Î²2GP-I) gene has been associated with anti-Î²2GP-I and thrombosis in patients with primary anti-phospholipid syndrome APS (PAPS). However, the cellular immune response to Î²2GP-I247 has been little studied.ObjectiveTo evaluate the immune cellular proliferation in response to native and non-native Î²2GP-I247 valine/leucine phenotype from Mexican patients with PAPS.MethodsWe studied 10 patients with PAPS and 10 healthy control subjects (HC). The polymorphism at position 247 of the Î²2GP-I gene was determined by PCR-RFLP and the corresponding Î²2GP-I protein was subsequently purified from normal human plasma by affinity chromatography. PBMC purified from patients and controls were stimulated with Î²2GP-I under native and in non native (reduced) conditions. We also determined the anti-Î²2GP-I production in vitro by B cell clones (EBV) generated in cocultures experiments. Differential Scanning Calorimetry (DSC) was studied to determine the structural differences between the Î²2GP-I247 valine/leucine isoforms. Cytokine profile (IL-2, IL-4, IL-6, TNFÎ±, INFÎ³) was evaluated in culture supernatants.ResultsPAPS and healthy control PBMCs had a higher proliferative response when stimulated with Î²2GP-I under reduced cultures conditions compared to non-denatured conditions. PBMCs response from PAPS patients was higher. We observed more cell proliferation in response to Î²2GP-I247 valine/leucine or valine isoforms in non-native conditions. In contrast, this response was not significant against Î²2GP-I247 leucine. These findings were T CD4+-dependent. Similar results were obtained with B cell clones derived from PAPS patients, which showed more pronounced proliferation in non native conditions and higher against Î²2GP-I247 valine. No differences were found in anti-Î²2GP-I production, but high levels of IL-6 in vitro were identified. The structural analysis of both Î²2GP-I247 isoforms by DSC showed a major conformational change due to a single mutation in the Î²2GP-I variants.ConclusionsPAPS PBMCs had a higher cellular response against Î²2GP-I247 in non-native culture conditions preferentially to the Î²2GP-I247 valine phenotype. This effect is T CD4+ dependent and appears to be driven by tertiary structural changes adopted by Î²2GP-I247 polymorphism.
Journal: Human Immunology - Volume 78, Issue 2, February 2017, Pages 146-152