Affiliation:
1. Department of Laboratory Medicine Catholic Kwandong University International St. Mary's Hospital Incheon Republic of Korea
2. Department of Laboratory Medicine, Seoul St. Mary's Hospital, College of Medicine The Catholic University of Korea Seoul Republic of Korea
3. Research and Development Institute for In Vitro Diagnostic Medical Devices of Catholic University of Korea Seoul Republic of Korea
4. Department of Biomedicine and Health Sciences, Graduate School The Catholic University of Korea Republic of Korea
5. Division of Nephrology, Department of Internal Medicine, Seoul St. Mary's Hospital, College of Medicine The Catholic University of Korea Seoul Republic of Korea
Abstract
We evaluated the effect of specific HLA alleles and haplotypes on cytomegalovirus (CMV)‐specific cell mediated immunity (CMI) in kidney transplant (KT) candidates. CMV‐specific ELISPOT against pp65 and IE‐1 antigens (hereafter referred to as pp65 and IE‐1, respectively) was performed in 229 seropositive KT candidates. We analyzed the results related to 44 selected HLA alleles (9 HLA‐A, 15 HLA‐B, 9 HLA‐C, and 11 HLA‐DR) and 13 HLA haplotypes commonly found in study participants. The pp65 and IE‐1 results in 229 seropositive candidates were 227.5 (114.5–471.5) and 41.0 (8.8–185.8) (median [interquartile range]) spots/2 × 105 PBMCs, respectively. The pp65 and IE‐1 results showed significant differences between candidates with different HLA alleles (A*02 vs. A*26 [p = 0.016], A*24 vs. A*30 [p = 0.031], B*07 vs. B*46 [p = 0.005], B*54 vs. B*35 [p = 0.041], B*54 vs. B*44 [p = 0.018], B*54 vs. B*51 [p = 0.025], and C*06 vs. C*14 [p = 0.034]). HLA‐A*02 and B*54 were associated with increased pp65 and IE‐1 results, respectively (p = 0.005 and p < 0.001, respectively). In contrast, the HLA‐A*26 and B*46 alleles were associated with a decreased pp65 response, whereas the A*30 allele was associated with a decreased IE‐1 response (p < 0.05). The pp65 results correlated with the HLA‐A allele frequencies (R = 0.7546, p = 0.019) and the IE‐1 results correlated with the HLA‐C allele frequencies of the study participants (R = 0.7882, p = 0.012). Among 13 haplotypes, HLA‐A*30 ~ B*13 ~ C*06 ~ DRB1*07 showed decreased CMV‐CMIs compared to the other HLA haplotypes, probably due to a combination of HLA alleles associated with lower CMV‐CMIs. Our results demonstrated that CMV‐specific CMIs may be influenced by the HLA allele as well as the HLA haplotype. To better predict CMV reactivation, it is important to estimate risk in the context of HLA allele and haplotype information.
Subject
Genetics,Immunology,Immunology and Allergy