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爱尔兰的巨细胞病毒感染:血清阳性率、HLA I类等位基因及影响

Cytomegalovirus Infection in Ireland: Seroprevalence, HLA Class I Alleles, and Implications.

作者信息

Hassan Jaythoon, O'Neill Derek, Honari Bahman, De Gascun Cillian, Connell Jeff, Keogan Mary, Hickey David

机构信息

From the National Virus Reference Laboratory, University College Dublin, Belfield, Dublin (JH, CDG, JC); National Histocompatibility and Immunogenetics Service for Solid Organ Transplantation, Beaumont Hospital, Dublin (DON, MK); Centre for Support and Training in Analysis and Research, Department of Public Health, Physiotherapy and Population Science, University College Dublin, Belfield, Dublin (BH); and Transplantation Unit, Beaumont Hospital, Dublin, Ireland (DH).

出版信息

Medicine (Baltimore). 2016 Feb;95(6):e2735. doi: 10.1097/MD.0000000000002735.

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 = 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 co-expressed 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 = 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.

摘要

巨细胞病毒(CMV)感染在全球范围内均有发生,初次感染通常发生在儿童早期,且往往没有症状,而成年人的初次感染可能会导致有症状的疾病。CMV会建立一种慢性潜伏感染,并伴有间歇性的再激活期。在免疫功能低下的人群中,初次感染或再激活与死亡率和发病率的增加有关。经胎盘传播可能会导致严重的出生缺陷或长期的感音神经性听力损失。我们开展了一项研究,以确定爱尔兰的CMV血清阳性率以及HLA I类等位基因与CMV感染频率之间的关联。对于1990年至2013年间1849名进行了HLA分型的实体器官移植供者队列,测定了CMV IgG(既往CMV感染的标志物)的存在情况。CMV IgG的存在与HLA类型相关。1990年至2013年期间,实体器官移植供者中的CMV血清阳性率为33.4%(每年范围为22%-48%)。多因素逻辑回归分析表明,年龄和HLA等位基因均与CMV血清阳性有关。观察到年龄与CMV血清阳性之间存在显著的正相关关系(OR = 1.013,P < 0.001,CI [1.007, 1.019])。卡方分析显示,女性性别与CMV血清阳性独立相关(P < 0.01)。育龄期女性(20 - 39岁)的血清阳性率显著高于同年龄男性(37%对26%,P < 0.01)。我们队列中HLA - A1、HLA - A2和HLA - A3的频率分别为40.8%、48.8%和25.9%。逻辑回归分析表明,HLA - A1的存在而非HLA - A2或HLA - A3与CMV血清阴性独立相关(P < 0.01)。有趣的是,共表达HLA - A2和HLA - A3等位基因的个体更有可能为CMV血清阳性(P < 0.02)。我们队列中HLA - B5、HLA - B7和HLA - B8的频率分别为

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fdf2/4753911/bd41a3e638b4/medi-95-e2735-g001.jpg

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