Abstract:
Host non-T cell markers to aid in the diagnosis of cryptococcal meningoencephalitis (CM) have not been identified. In this case-control study, we characterized antibody and B cell profiles in HIV-negative and HIV-positive Vietnamese individuals of the Kinh ethnicity recently diagnosed with CM and controls. The study included 60 HIV-negative with no known immunocompromising condition and 60 HIV-positive individuals, with 30 CM cases and 30 controls in each group. Participants were matched by age, sex, HIV serostatus, and CD4 count in the HIV-positive group. Plasma immunoglobulin (Ig) levels, including IgG1, IgG2, IgM, and IgA, Cryptococcus spp. glucuronoxylomannan (GXM)- and laminarin (branched ${\\rm{\\beta }}$-[1-3]-glucan)-binding IgG, IgM, IgA levels, and peripheral blood B cell subsets were measured. Logistic regression, principal component, and mediation analyses were conducted to assess associations between antibody, B cell levels, and CM. The results showed that GXM-IgG levels were higher and IgG1 and IgG2 were lower in CM cases than controls, regardless of HIV status. In HIV-negative individuals, IgG2 mediated an inverse association between CD19+CD27+CD43+CD5- (B-1b-like) cells and CM. In HIV-positive individuals, lower levels of IgA, laminarin-IgA, and CD19+CD27+IgM+IgD- (IgM+ memory B) cells were each associated with CM. The shared and distinct antibody and B cell profiles identified in HIV-negative and HIV-positive CM cases may inform the identification of non-T-cell markers of CM risk or unsuspected disease, particularly in HIV-negative individuals.
Unlike cryptococcal meningitis (CM) in HIV-positive individuals, there are no known biomarkers of risk in HIV-negative individuals and the diagnosis is often not suspected and delayed. This study identified non-T cells, including antibody and B cell CM-associated profiles that may guide cryptococcal antigen testing in HIV-negative individuals.
摘要:
尚未鉴定出有助于诊断隐球菌性脑膜脑炎(CM)的宿主非T细胞标志物。在这项病例对照研究中,我们对最近诊断为CM的Kinh族HIV阴性和HIV阳性越南个体和对照者的抗体和B细胞谱进行了表征。该研究包括60名HIV阴性,没有已知的免疫受损状况和60名HIV阳性个体,每组30例,对照组30例。参与者按年龄匹配,性别,艾滋病毒血清状态,HIV阳性组的CD4计数。血浆免疫球蛋白(Ig)水平,包括IgG1、IgG2、IgM、还有IgA,隐球菌属。葡糖醛酸木甘露聚糖(GXM)-和海带多糖(支链${\\\rm{\\beta}}$-[1-3]-葡聚糖)-结合IgG,IgM,IgA水平,测定外周血B细胞亚群。Logistic回归,主成分,和调解分析进行评估抗体之间的关联,B细胞水平,和CM。结果显示,CM患者的GXM-IgG水平高于对照组,IgG1和IgG2水平低于对照组,无论艾滋病毒状况如何。在艾滋病毒阴性的个体中,IgG2介导CD19+CD27+CD43+CD5-(B-1b样)细胞与CM之间的反向关联。在艾滋病毒阳性者中,IgA水平较低,laminarin-IgA,CD19+CD27+IgM+IgA-(IgM+记忆B)细胞均与CM相关。在HIV阴性和HIV阳性CM病例中鉴定出的共有和不同的抗体和B细胞谱可能有助于鉴定CM风险或未怀疑的疾病的非T细胞标志物。特别是在HIV阴性个体中。
与HIV阳性个体的隐球菌性脑膜炎(CM)不同,在HIV阴性个体中没有已知的风险生物标志物,诊断通常不会被怀疑和延迟.这项研究确定了非T细胞,包括抗体和B细胞CM相关谱,可以指导HIV阴性个体的隐球菌抗原检测。