Shengping Hou1, Jian Qi1, Dan Liao1, Jing Fang1, Lu Chen1, Aize Kijlstra2, Peizeng Yang1. 1. The First Affiliated Hospital of Chongqing Medical University, Chongqing, China Chongqing Key Laboratory of Ophthalmology, Chongqing, China Chongqing Eye Institute, Chongqing, China. 2. University Eye Clinic Maastricht, Maastricht, The Netherlands.
Abstract
AIMS: Considering the phenotypical consequences and association of C4 copy number variation (CNV) with various autoimmune diseases, we aimed to examine C4 CNVs for 1027 patients with Vogt-Koyanagi-Harada (VKH) syndrome and 2083 controls. METHODS: C4 CNVs were examined by real-time PCR for 1027 patients with VKH and 2083 controls. Peripheral blood mononuclear cells (PBMC) were prepared from venous blood by Ficoll-Hypaque density-gradient centrifugation for cell culture. Cytokine production was examined by ELISA. RESULTS: The expression of total C4 in serum was significantly decreased in patients with VKH as compared with controls (p=0.0010). A significant positive association between C4 expression with C4 CNVs was found (p=0.0023, r(2)=0.92). CNV analysis identified significantly decreased frequencies of more than two copies of C4A or more than four copies of total C4 in patients with VKH (Pc=1.42×10(-3) to 3.56×10(-4), OR=0.67 to 0.70). Linkage analysis showed the independent association of C4 with VKH syndrome from human leucocyte antigen (HLA)-DR4. No significant association was observed concerning type 1 T helper cell (Th1) cytokines and Th17 cytokine production by stimulated PBMCs and C4A copy number. CONCLUSIONS: Our findings indicate a decreased expression of serum C4 and a decreased frequency of high C4 gene copy number in patients with VKH. TRIAL REGISTRATION NUMBER: Chinese Clinical Trial Registration Number: ChiCTR-CCC-12002184. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.
AIMS: Considering the phenotypical consequences and association of C4 copy number variation (CNV) with various autoimmune diseases, we aimed to examine C4 CNVs for 1027 patients with Vogt-Koyanagi-Harada (VKH) syndrome and 2083 controls. METHODS:C4 CNVs were examined by real-time PCR for 1027 patients with VKH and 2083 controls. Peripheral blood mononuclear cells (PBMC) were prepared from venous blood by Ficoll-Hypaque density-gradient centrifugation for cell culture. Cytokine production was examined by ELISA. RESULTS: The expression of total C4 in serum was significantly decreased in patients with VKH as compared with controls (p=0.0010). A significant positive association between C4 expression with C4 CNVs was found (p=0.0023, r(2)=0.92). CNV analysis identified significantly decreased frequencies of more than two copies of C4A or more than four copies of total C4 in patients with VKH (Pc=1.42×10(-3) to 3.56×10(-4), OR=0.67 to 0.70). Linkage analysis showed the independent association of C4 with VKH syndrome from human leucocyte antigen (HLA)-DR4. No significant association was observed concerning type 1 T helper cell (Th1) cytokines and Th17 cytokine production by stimulated PBMCs and C4A copy number. CONCLUSIONS: Our findings indicate a decreased expression of serum C4 and a decreased frequency of high C4 gene copy number in patients with VKH. TRIAL REGISTRATION NUMBER: Chinese Clinical Trial Registration Number: ChiCTR-CCC-12002184. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.
Authors: Katherine E Lintner; Yee Ling Wu; Yan Yang; Charles H Spencer; Georges Hauptmann; Lee A Hebert; John P Atkinson; C Yung Yu Journal: Front Immunol Date: 2016-02-15 Impact factor: 7.561
Authors: Shengping Hou; Zi Ye; Dan Liao; Lin Bai; Yunjia Liu; Jun Zhang; Aize Kijlstra; Peizeng Yang Journal: Sci Rep Date: 2016-01-28 Impact factor: 4.379