Role of Mannose-Binding Lectin Deficiency in HIV-1 and <i>Schistosoma</i> Infections in a Rural Adult Population in Zimbabwe

Background Polymorphism in the MBL2 gene lead to MBL deficiency, which has been shown to increase susceptibility to various bacterial, viral and parasitic infections. We assessed role of MBL deficiency in HIV-1 and schistosoma infections in Zimbabwean adults enrolled in the Mupfure Schistosomiasis and HIV Cohort (MUSH Cohort). Methods HIV-1, S. haematobium and S. mansoni infections were determined at baseline. Plasma MBL concentration was measured by ELISA and MBL2 genotypes determined by PCR. We calculated and compared the proportions of plasma MBL deficiency, MBL2 structural variant alleles B (codon 54A>G), C (codon 57A>G), and D (codon 52T>C) as well as MBL2 promoter variants -550(H/L), -221(X/Y) and +4(P/Q) between HIV-1 and schistosoma co-infection and control groups using Chi Square test. Results We assessed 379 adults, 80% females, median age (IQR) 30 (17–41) years. HIV-1, S. haematobium and S. mansoni prevalence were 26%, 43% and 18% respectively in the MUSH baseline survey. Median (IQR) plasma MBL concentration was 800μg/L (192-1936μg/L). Prevalence of plasma MBL deficiency was 18% with high frequency of the C (codon 57G>A) mutant allele (20%). There was no significant difference in median plasma MBL levels between HIV negative (912μg/L) and HIV positive (688μg/L), p = 0.066. However plasma MBL levels at the assay detection limit of 20μg/L were more frequent among the HIV-1 infected (p = 0.007). S. haematobium and S. mansoni infected participants had significantly higher MBL levels than uninfected. All MBL2 variants were not associated with HIV-1 infection but promoter variants LY and LL were significantly associated with S. haematobium infection. Conclusion Our data indicate high prevalence of MBL deficiency, no evidence of association between MBL deficiency and HIV-1 infection. However, lower plasma MBL levels were protective against both S. haematobium and S. mansoni infections and MBL2 promoter and variants LY and LL increased susceptibility to S. haematobium infection.背景：MBL2基因的多态性可导致甘露聚糖结合凝集素（MBL）缺乏，现有研究证实该情况会增加个体对多种细菌、病毒及寄生虫感染的易感性。本研究针对纳入津巴布韦Mupfure血吸虫病与HIV队列（MUSH队列）的成年人，评估MBL缺乏在HIV-1与血吸虫感染中的作用。 方法：在基线阶段对受试者的HIV-1、埃及血吸虫（S. haematobium）及曼氏血吸虫（S. mansoni）感染情况进行检测。采用酶联免疫吸附试验（ELISA）检测血浆MBL浓度，通过聚合酶链式反应（PCR）确定MBL2基因型。采用卡方检验，计算并比较HIV-1与血吸虫共感染组及对照组的血浆MBL缺乏率、MBL2结构变异等位基因B（密码子54A>G）、C（密码子57A>G）、D（密码子52T>C）以及MBL2启动子变异-550(H/L)、-221(X/Y)和+4(P/Q)的占比。 结果：本研究共纳入379名成年人，其中80%为女性，年龄中位数（四分位间距，IQR）为30（17~41）岁。在MUSH队列基线调查中，HIV-1、埃及血吸虫及曼氏血吸虫的感染率分别为26%、43%与18%。血浆MBL浓度中位数（四分位间距）为800μg/L（192~1936μg/L）。血浆MBL缺乏的发生率为18%，其中C等位基因（密码子57G>A）突变型的携带频率较高（20%）。HIV阴性组与HIV阳性组的血浆MBL水平中位数分别为912μg/L与688μg/L，组间差异无统计学意义（p=0.066）。但当检测下限为20μg/L时，HIV-1感染者的血浆MBL水平达到检测下限的比例更高（p=0.007）。埃及血吸虫与曼氏血吸虫感染者的血浆MBL水平显著高于未感染者。所有MBL2结构变异均与HIV-1感染无显著关联，但启动子变异LY及LL型与埃及血吸虫感染显著相关。 结论：本研究数据显示MBL缺乏的发生率较高，未发现MBL缺乏与HIV-1感染存在关联的证据。然而，较低的血浆MBL水平对埃及血吸虫及曼氏血吸虫感染均具有保护作用，而MBL2启动子变异LY及LL型会增加埃及血吸虫感染的易感风险。