Cellular immune response to β 2 -glycoprotein-I valine/leucine 247 phenotypes in Mexican patients with primary antiphospholipid syndrome.

Autor: Núñez-Álvarez CA; Department of Immunology and Rheumatology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico., Hernández-Ramírez DF; Department of Immunology and Rheumatology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico., Martinez-Castillo A; Department of Immunology and Rheumatology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico., Pascual Ramos V; Department of Immunology and Rheumatology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico., Cabiedes J; Department of Immunology and Rheumatology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico., Ortega A; Department of Biochemistry, School of Medicine, Universidad Nacional Autónoma de México, Mexico City, Mexico; Department of Biochemistry, Instituto Nacional de Perinatología, Mexico City, Mexico. Electronic address: aortega@unam.mx., Cabral AR; Department of Immunology and Rheumatology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico. Electronic address: arcabral1952@gmail.com.
Jazyk: angličtina
Zdroj: Human immunology [Hum Immunol] 2017 Feb; Vol. 78 (2), pp. 146-152. Date of Electronic Publication: 2016 Dec 27.
DOI: 10.1016/j.humimm.2016.12.008
Abstrakt: Homozygote genotype V 247 of the β 2 -glycoprotein-I (β 2 GP-I) gene has been associated with anti-β 2 GP-I and thrombosis in patients with primary anti-phospholipid syndrome APS (PAPS). However, the cellular immune response to β 2 GP-I 247 has been little studied.
Objective: To evaluate the immune cellular proliferation in response to native and non-native β 2 GP-I 247 valine/leucine phenotype from Mexican patients with PAPS.
Methods: We studied 10 patients with PAPS and 10 healthy control subjects (HC). The polymorphism at position 247 of the β 2 GP-I gene was determined by PCR-RFLP and the corresponding β 2 GP-I protein was subsequently purified from normal human plasma by affinity chromatography. PBMC purified from patients and controls were stimulated with β 2 GP-I under native and in non native (reduced) conditions. We also determined the anti-β 2 GP-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 β 2 GP-I 247 valine/leucine isoforms. Cytokine profile (IL-2, IL-4, IL-6, TNFα, INFγ) was evaluated in culture supernatants.
Results: PAPS and healthy control PBMCs had a higher proliferative response when stimulated with β 2 GP-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 β 2 GP-I 247 valine/leucine or valine isoforms in non-native conditions. In contrast, this response was not significant against β 2 GP-I 247 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 β 2 GP-I 247 valine. No differences were found in anti-β 2 GP-I production, but high levels of IL-6 in vitro were identified. The structural analysis of both β 2 GP-I 247 isoforms by DSC showed a major conformational change due to a single mutation in the β 2 GP-I variants.
Conclusions: PAPS PBMCs had a higher cellular response against β 2 GP-I 247 in non-native culture conditions preferentially to the β 2 GP-I 247 valine phenotype. This effect is T CD4 + dependent and appears to be driven by tertiary structural changes adopted by β 2 GP-I 247 polymorphism.
(Copyright © 2016 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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