Cytomegalovirus infection in Ireland: Seroprevalence, HLA Class I alleles and implications

Abstract

Cytomegalovirus (CMV) infections occur worldwide and primary infection usually occurs in early childhood and is often asymptomatic whereas primary infection in adults may result in symptomatic illness. CMV establishes a chronic latent infection with intermittent periods of reactivation. Primary infection or reactivation associate with increased mortality and morbidity in those who are immunocompromised. Transplacental transmission may result in significant birth defects or long-term sensorineural hearing loss.We performed a study to determine the CMV seroprevalence and the association between HLA Class I alleles and frequency of CMV infection in Ireland. The presence of CMV IgG, a marker of previous CMV infection, was determined for a cohort of 1849 HLA typed solid organ transplant donors between 1990 and 2013. The presence of CMV IgG was correlated with HLA type.The CMV seroprevalence in solid organ transplant donors was 33.4% (range 22-48% per annum) over the time period 1990 to 2013. Multivariate logistic regression analysis showed that both age and HLA alleles were associated with CMV seropositivity. A significant and positive relationship between age and CMV seropositivity was observed (OR ¼ 1.013, P < 0.001, CI [1.007, 1.019]). Chi-square analysis revealed that the female gender was independently associated with CMV seropositivity (P < 0.01). Seroprevalence in women of reproductive age (20-39 years) was significantly higher than men of the same age (37% vs 26%, P < 0.01). The frequencies of HLA-A1, HLA-A2, and HLA-A3 in our cohort were 40.8%, 48.8%, and 25.9%, respectively. Logistic regression analysis showed that the presence of HLA-A1 but not HLA-A2 or HLA-A3 was independently associated with CMV seronegativity (P < 0.01). Interestingly, individuals who coexpressed HLA-A2 and HLA-A3 alleles were significantly more likely to be CMV seropositive (P < 0.02). The frequencies of HLA-B5, HLA-B7, and HLA-B8 in our cohort were 6.1%, 31.2%, and 30.8%, respectively. The presence of the most common inherited haplotype in the Irish population, HLA-A1, B8 was significantly associated with CMV seronegativity (OR ¼ 1.278, P < 0.001, CI [1.049, 1.556]).CMV seroprevalence is lower in Ireland compared with other countries. The high frequency of HLA-A1 in the Irish population may, in part, have a role in the reduced susceptibility to CMV infection.(Medicine 95(6):e2735)Abbreviations: CI = confidence interval, CMV = cytomegalovirus, HLA = human leucocyte antigen, IFN = interferon, Ig = immunoglobulin, OR = odds ratios.

HLA-C*04:01 Affects HLA Class I Heterozygosity and Predicted Affinity to SARS-CoV-2 Peptides, and in Combination With Age and Sex of Armenian Patients Contributes to COVID-19 Severity

“…HLA molecules play a pivotal role in the development and regulation of immune response and are shown to be associated with the predisposition to multiple viral diseases, such as HIV (7,8), HBV, HCV (9), CMV (10), and SARS-CoV-1 (11)(12)(13)(14). Several studies have reported a link between HLA alleles and COVID-19 infection in different populations (15)(16)(17)(18)(19)(20), some of which also indicated the association between an HLA-C allele and the severe clinical course of the disease (17,19,21,22).…”

The effect of human leukocyte antigen A1 and B35‐Cw4 on sustained BK polyomavirus DNAemia after renal transplantation

“…The effect of HLA-A1 has been shown in post-transplant viral infections such as the Epstein-Barr virus (EBV), 47 herpes simplex virus (HSV), 48 and cytomegalovirus (CMV). 49 HLA-A1 is known as a ligand of KIRs. 50 Further studies are required to show the effect of HLA-A1 relative to other gene alleles in the vicinity of the A1 gene.…”

“…In this cohort, HLA‐A1 was also significantly associated with post‐transplant sustained BKPyV DNAemia and this effect remained considerable in multivariate analysis. The effect of HLA‐A1 has been shown in post‐transplant viral infections such as the Epstein‐Barr virus (EBV), 47 herpes simplex virus (HSV), 48 and cytomegalovirus (CMV) 49 . HLA‐A1 is known as a ligand of KIRs 50 .…”

Clinical Features and Diagnosis of Anterior Segment Inflammation Related to Cytomegalovirus in Immunocompetent African, Asian, and Caucasian Patients

“…5,34 Most genotypes determined so far are probably distributed worldwide. 5,32,[34][35][36][37][38][39][40][41] In this study, a long period of time was observed (67 months) between symptom onset and diagnosis of HCMV infection. In France, when the condition becomes chronic after each episode, HCMV anterior uveitis is diagnosed by aqueous tap analysis, mainly using GWc testing.…”