Ogola George O, Ouma Collins, Jura Walter G Z O, Muok Erick O, Colebunders Robert, Mwinzi Pauline N
Maseno University, Maseno, Kenya.
BMC Infect Dis. 2014 Jun 10;14:316. doi: 10.1186/1471-2334-14-316.
Human Immunodeficiency Virus (HIV) and Schistosomiasis co-infection is common among residents at the shores of Lake Victoria in Kenya. About 36% of this population initiating antiretroviral therapy (ART) experience Immune Reconstitution Inflammatory Syndrome (IRIS) that complicates recovery. Several IL-23R alleles have been associated with susceptibility to both autoimmune and inflammatory diseases through T-helper type 17 (TH17) cells. However, whether or not variants within the IL-23R increase susceptibility to IRIS in western Kenya is unknown. The objective of the current study was to determine the association between IL-23R gene polymorphisms, CD4+ cell counts and HIV RNA levels and IRIS in HIV and Schistosoma mansoni co-infected patients undergoing highly active anti-retroviral therapy (HAART).
A three-month case-control study was conducted on antiretroviral naïve schistosomiasis/HIV co-infected fishermen starting HAART in Uyoma Rarieda, Siaya County, Kenya. Seventy one patients were sampled at baseline and followed up for three months, to establish if they developed Schistosoma-related IRIS. In addition, the CD4+ cell counts and HIV RNA levels were determined in pre- and post-administration of HAART. Variations at five polymorphic sites of IL-23R (rs1884444, rs11465754, rs6682925, rs7530511 and rs7539625) based on >10% minor allele frequency in Yoruban reference population was determined using Allelic Discrimination Assay. The association between the five variants and susceptibility to IRIS was determined using logistic regression while controlling for potential confounders. In addition, the functional differences between the baseline CD4 + Cell counts and viral loads were determined using medians while across IL-23R genotypes were determined using Kruskal-Wallis tests.
Overall, 26 (36.6%) patients developed schistosomiasis-associated IRIS at a median age of 35.5 years. Carriage of the TT genotype at the non-synonymous rs1884444 T > G relative to GG, was associated with a decreased risk of schistosomiasis-associated IRIS (OR, 0.25, 95% CI, 0.07-0.96, P = 0.043) while both baseline CD4+ cell counts and viral loads had no association with IRIS.
These findings indicate that the non-synonymous variant rs1884444 T > G of IL-23R is associated with a decreased risk to schistosomiasis-associated IRIS. However, additional studies in a larger cohort and with an all inclusive polymorphic variants in the synonymous and non-synonymous regions need to be evaluated.
人类免疫缺陷病毒（HIV）与血吸虫病合并感染在肯尼亚维多利亚湖沿岸居民中很常见。约36%开始接受抗逆转录病毒治疗（ART）的该人群会经历免疫重建炎症综合征（IRIS），这使康复变得复杂。几个白细胞介素23受体（IL-23R）等位基因已通过17型辅助性T细胞（TH17）与自身免疫性疾病和炎症性疾病的易感性相关。然而，在肯尼亚西部，IL-23R内的变异是否会增加对IRIS的易感性尚不清楚。本研究的目的是确定在接受高效抗逆转录病毒治疗（HAART）的HIV与曼氏血吸虫合并感染患者中，IL-23R基因多态性、CD4 +细胞计数、HIV RNA水平与IRIS之间的关联。
在肯尼亚锡亚县拉里达Uyoma对开始接受HAART的未接受过抗逆转录病毒治疗的血吸虫病/HIV合并感染渔民进行了为期三个月的病例对照研究。71名患者在基线时进行采样，并随访三个月，以确定他们是否发生与血吸虫病相关的IRIS。此外，在HAART给药前和给药后测定CD4 +细胞计数和HIV RNA水平。基于约鲁巴参考人群中>10%的次要等位基因频率，使用等位基因鉴别分析确定IL-23R五个多态性位点（rs1884444、rs11465754、rs6682925、rs7530511和rs7539625）的变异。在控制潜在混杂因素的同时，使用逻辑回归确定五个变异与IRIS易感性之间的关联。此外，使用中位数确定基线CD4 +细胞计数和病毒载量之间的功能差异，而使用Kruskal-Wallis检验确定跨IL-23R基因型的差异。
总体而言，26名（36.6%）患者在中位年龄35.5岁时发生了与血吸虫病相关的IRIS。相对于GG，非同义rs1884444 T>G处TT基因型的携带与血吸虫病相关IRIS的风险降低相关（比值比，0.25；95%置信区间，0.07 - 0.96；P = 0.043），而基线CD4 +细胞计数和病毒载量与IRIS均无关联。
这些发现表明，IL-23R的非同义变异rs1884444 T>G与血吸虫病相关IRIS的风险降低相关。然而，需要在更大的队列中进行进一步研究，并评估同义区和非同义区所有包含的多态性变异。
