Abstract
Purpose :
Purpose: Cytomegalovirus (CMV) infection is associated with recurrent anterior uveitis (AU) in immunocompetent individuals. As the Major Histocompatibility Complex Class I restricted CD8 T-cell response is an important immune defense mechanism against CMV infection, we hypothesize that human leukocyte antigen (HLA) class I proteins may confer susceptibility towards or protection against CMV ocular infection. We compared class I allelic frequencies of immunocompetent Chinese individuals with CMV AU disease with that of reported Chinese population controls.
Methods :
Methods: Genomic DNA was isolated from venous blood samples of 124 immunocompetent Singaporean Chinese individuals with aqueous humor PCR proven CMV AU. HLA class I A, B, C typing was performed by Next Generation
Sequencing on a MiSeq using Conexio’s Capture HLATM protocol and Assign MPS (Conexio Genomics PTE LTD, Perth, Australia). Allelic frequencies were compared with that of Chinese population controls (total N=18,413) on database from Southern China, Hong Kong, Taiwan, Malaysia and Singapore using Pearson’s χ2 or Fisher’s Exact test with Bonferroni correction. Haplotype inference was performed using Arlequin V3.5.
Results :
Results: HLA-B*5101 and C*1402 were significantly associated with CMV uveitis patients compared to Chinese population controls (allelic frequencies 0.1048 vs 0.0424, P-value with Bonferroni correction Pc=4.0e-05; 0.0726 vs 0.0357, Pc=0.039 respectively). On the contrary, HLA-A*0201 was less common among patients (0.0726 vs 0.1601, Pc=0.003). The second and fourth most frequent haplotypes among CMV uveitis patients showed a strong association with the disease compared to controls (A*1101-B*4001-C*0702: 7.9 vs 3.6%, P=0.008, relative risk RR=2.38; and A*1101-B*5101-C*1402: 4.1 vs 1.1%, P=0.002, RR=3.87).
Conclusions :
Conclusions: Our data suggests that B51:01-C*14:02 haplotype may indicate susceptibility towards CMV uveitis among Chinese, in keeping with its higher reported frequencies among Orientals populations (3.6-4.7%), compared to Caucasians (≤1.9%), Hispanics (≤1.3%) and African Americans (≤0.04%) populations. Further studies are necessary to understand its impact on the immune response against CMV.B*51:01 and C*14:02 are in strong linkage disequilibrium and our result implies this haplotype may affect anti-CMV immunity.
This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.