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Jay Jyh-Kuen Siak, Nobuyo Yawata, Xinru Lim, Kaing Woon, Anne Jansen, Samanthila Waduthantri, Soon-Phaik Chee; Human Leukocyte Antigen Risk Alleles among Chinese with Cytomegalovirus Anterior Uveitis. Invest. Ophthalmol. Vis. Sci. 2017;58(8):2146. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
Cytomegalovirus (CMV) infection is associated with recurrent acute or chronic anterior uveitis (AU) in immunocompetent individuals, especially among Chinese populations. Major Histocompatibility Complex Class I restricted CD8 T-cell response is a major immune defense against CMV reactivation, and different human leukocyte antigen (HLA) class I alleles can confer different levels of CD8+T-cell protection against CMV-associated diseases. To test our hypothesis that recurrent CMV AU might be related to an impaired immune defense, we compared HLA class I alleles of immunocompetent Chinese individuals with CMV AU against the reported allele frequencies of Chinese population controls to identify HLA allelic associations.
Genomic DNA was isolated from venous blood samples of 104 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). Haplotype inference was performed using Arlequin V3.5 and haplotype frequencies were compared with that of Chinese population controls on Database using Pearson’s Chi-square test with Bonferroni correction.
HLA-B*3501, B*5101, B*5401, C*0403 and C*1402 were more frequent among CMV AU patients compared to population controls (3.8 vs 0%, 11.4 vs 3.4%, 7.1 vs 0%, 2.9 vs 0%, 8.7 vs 2.9%; Pc-values after Bonferroni correction=0.009, 0.004, <0.001, 0.031, 0.036 respectively). A significant difference was not found between CMV AU patients and controls for frequencies of HLA-A (P>0.05). A1101-B5101-C1402, the fourth most frequent haplotype in CMV-AU, showed a strong association with CMV-AU compared to the database (4.3 versus 1.1%, Pc-value=0.0004).
Conclusion: Our data suggests that HLA-B*3501, B*5101, B*5401, C*0403, C*1402 and, A1101-B5101-C1402 haplotypes are associated with CMV AU, and these are more dominant among Chinese compared to Caucasians. Considering that B5101-C1402 is also associated with Posner Schlossman syndrome, the haplotype may have significant impact on the immune response of the disease entity. Further studies are needed to validate our observation.
This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.
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