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Zhang Z.,Beijing 307 Hospital Affiliated to Academy of Medical science | Zhang Z.,Institute of Beijing 307 Hospital | Dai D.,Beijing 307 Hospital Affiliated to Academy of Medical science | Dai D.,Institute of Beijing 307 Hospital | And 15 more authors.
Tissue Antigens | Year: 2014

This study investigated the genetic polymorphisms of HLA-B27, together with polymorphisms on endoplasmic reticulum aminopeptidase 1 (ERAP1), and susceptibility for ankylosing spondylitis (AS) in the Beijing Han population. A case-control study was carried out for 602 AS patient samples and 619 matched controls of Han Chinese. HLA-B27 genotyping was performed by polymerase chain reaction-sequence specific primers (PCR-SSP), and four ERAP1 SNPs (rs27037, rs27980, rs27582, and rs27434) were selected and genotyped on the Sequenom iPlex platform (Sequenom, San Diego, CA). Association analysis was performed using the likelihood ratio χ2 test. This study identified four HLA-B27 alleles in Beijing Han AS patients, B*27:02, B*27:04, B*27:05, and B*27:07, of which B*27:05 was the most significant geographical different subtype among AS patients in Chinese. Our results confirmed that HLA-B27 was strongly associated with AS (P=1.9×10-150), and the most strongly associated alleles were B*27:04, B*27:05, and B*27:02. Our study also confirmed a weak association between ERAP1 (rs27434) and AS. We also observed that for HLA-B*27:02 and HLA-B*27:04 positive AS patients, rs27434 and rs27582 were associated with AS. In contrast, for HLA-B27-negative and HLA-B*27:05-positive AS patients, this association was not observed. This is the first study to show that both B27 and ERAP1 are AS genetic susceptibility genes in Beijing Han. Interactions between ERAP1 and HLA-B*27:02 and B*27:04 may play an important role in the AS pathogenesis. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd. Source

Zhang Z.,Beijing 307 Hospital Affiliated to Academy of Medical science | Zhang Z.,Institute of Beijing 307 Hospital | Yu K.,Beijing 307 Hospital Affiliated to Academy of Medical science | Yu K.,Institute of Beijing 307 Hospital | And 8 more authors.
Clinical Rheumatology | Year: 2016

This study investigated the role of anthrax toxin receptor 2 (ANTXR2) gene polymorphisms and capillary morphogenesis protein 2 (CMG2) expression in susceptibility and pathogenesis to ankylosing spondylitis (AS) in the Han Chinese in Beijing. A case-control study was performed using 602 AS patient samples meeting the revised New York criterion and 619 matched controls from Han Chinese individuals. Nineteen single-nucleotide polymorphisms (SNPs) of ANTXR2 genes were selected and genotyped using the Sequenom iPlex platform. Real-time polymerase chain reaction and flow cytometry were performed to investigate the impact of SNP polymorphisms on ANTXR2 transcription and CMG2 expression, respectively. The association of variants with AS was examined with UNPHASED 3.1.5. A novel association was observed between AS and three SNPs in the ANTXR2 gene (rs4690127, rs6823031, and rs4333130; P = 0.004, 0.011, and 0.013, respectively), confirming the association between rs433130 and AS in the Han Chinese. The strongest haplotype association was observed with rs4690127-rs6823031-rs4333130 (P = 2.5 × 10−4). rs6534639 and rs4333130 showed a cis-interaction (P = 0.027) in AS. ANTXR2 messenger RNA (mRNA) expression was significantly higher in the AS group than in the control group (P = 0.039). CMG2 expression in the lipopolysaccharide (LPS)-stimulated group was significantly lower than that in the control group (P = 0.018). This study reports a novel association between ANTXR2 and AS in the Han Chinese. ANTXR2 genetic polymorphisms affect ANTXR2 mRNA transcription and CMG2 expression. The opposing results observed for ANTXR2 transcription and CMG2 expression suggest a complex role of ANTXR2 polymorphisms in AS pathogenesis. © 2016 International League of Associations for Rheumatology (ILAR) Source

Luo Y.,Beijing 307 Hospital Affiliated to Academy of Medical science | Liang F.,Beijing 307 Hospital Affiliated to Academy of Medical science | Liu N.,Beijing 307 Hospital Affiliated to Academy of Medical science | Xue H.,Beijing 307 Hospital Affiliated to Academy of Medical science | And 6 more authors.
Journal of Immunotherapy | Year: 2013

A major challenge associated with allogeneic hematopoietic stem cell transplantation is effective prevention and/or attenuation of symptoms associated with acute graft-versus-host disease (aGVHD) that can result from a failure of either host and/or donor CD4CD25 regulatory T (Tr) and CD8CD28 suppressor T (Ts) cells to dampen immunopathogenic responses mediated by alloreactive donor CD4CD28 Th1 (Th1) and CD8CD28 Tc1 (Tc1) cell-mediated inflammatory processes. Considering the crucial role of CD28/B7-1 costimulatory signal pathway in development, activation, differentiation, and function of these T subsets, we developed a targeted DNA vaccine encoding the Pseudomonas exotoxin-A and the B7-1 molecule that could act as both an antagonist to Th1-mediated and Tc1-mediated responses while concomitantly acting as an agonist stimulating Tr-mediated and Ts-mediated responses as a strategy for reducing aGVHD-associated lethality. A single intramuscular injection with this vaccine significantly increased Tr and Ts levels in a murine aGVHD model. In addition, immunized mice presented with significantly diminished Th1-cytokines interferon-γ and interleukin-2 response and a moderately upregulated Th2-cytokine interleukin-10 and Th3-cytokine transforming growth factor-β response. More importantly, vaccination significantly reduced aGVHD, measured by significantly extended mean survival times, decreased mean weight loss, recovery of peripheral leukocyte numbers, disease presentation associated with mild-moderate histopathologic changes, a balanced Th1-Th2-Th3-cytokine responses and functional Tr-mediated and Ts-mediated regulatory/suppressor mechanisms at levels more potent than observed in animals treated with cyclosporine A+methotrexate. Our data first provide the proof-of-principal that B7-1-PE40KDEL targeted DNA vaccine represents a prophylactic approach for reducing alloreactive Th1-mediated and Tc-mediated aGVHD lethality by CD28/B7-1 axis. © 2013 by Lippincott Williams & Wilkins. Source

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