Background Asymptomatic cryptococcal antigenemia (positive blood cryptococcal antigen [CrAg]) is associated with increased mortality in HIV-positive individuals even after adjusting for CD4 count and despite receiving antifungal treatment. The association of antibody immunity with mortality in HIV-positive adults with cryptococcal antigenemia is unknown. Methods Cryptococcus spp. capsular glucuronoxylomannan (GXM)- and naturally occurring β-glucans (laminarin, curdlan)-binding antibodies were measured in blood samples of 197 South Africans living with HIV who underwent CrAg screening and were prospectively followed up to 6 months. Associations between antibody titers, CrAg status and all-cause mortality were sought using logistic and Cox proportional hazards regression, respectively. Results Compared to CrAg-negative (n = 130), CrAg-positive individuals (n = 67) had significantly higher IgG1 (median, 6,672 [interquartile range, IQR, 4,696-10,414] vs. 5,343 [3,808-7,722]μg/ml; P = 0.007), IgG2 (1,467 [813-2,607] vs. 1,036 [519-2,012]μg/ml; P = 0.01), GXM-IgG (1:170 [61-412] vs. 1:117 [47-176]; P = 0.0009) and lower curdlan-IgG (1:47 [11-133] vs. 1:93 [40-206]; P = 0.01) titers. GXM-IgG associated directly with cryptococcal antigenemia adjusted for CD4 count and antiretroviral therapy use (odds ratio, 1.64 for each log increase in titer; 95% confidence interval [CI], 1.21-2.22). Among CrAg-positive individuals, GXM-IgG inversely associated with mortality at 6 months adjusted for CD4 count and active or prevalent tuberculosis (hazard ratio, 0.50; a two-fold reduction per log increase in titer; 95% CI, 0.33-0.77). Conclusions The finding of an inverse association of GXM-IgG with mortality in CrAg-positive individuals suggests that GXM-IgG titer may have prognostic value in such individuals. Prospective longitudinal studies of antibody levels to investigate this hypothesis and identify mechanisms by which antibody may protect against mortality are warranted.

中文翻译：

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南非晚期艾滋病患者队列中抗体免疫与隐球菌抗原血症和死亡率的关系


背景 无症状隐球菌抗原血症（血液隐球菌抗原 [CrAg] 阳性）与 HIV 阳性个体的死亡率增加相关，即使在调整 CD4 计数并接受抗真菌治疗后也是如此。抗体免疫与隐球菌抗原血症 HIV 阳性成人死亡率的关系尚不清楚。方法隐球菌属。在 197 名南非 HIV 感染者的血液样本中测量了荚膜葡糖醛酸木甘露聚糖 (GXM) 和天然存在的 β-葡聚糖（昆布多糖、凝乳多糖）结合抗体，这些人接受了 CrAg 筛查，并进行了长达 6 个月的前瞻性随访。分别使用 Logistic 和 Cox 比例风险回归来寻找抗体滴度、CrAg 状态和全因死亡率之间的关联。结果 与 CrAg 阴性 (n = 130) 相比，CrAg 阳性个体 (n = 67) 的 IgG1 显着较高（中位数为 6,672 [四分位距，IQR，4,696-10,414] vs. 5,343 [3,808-7,722]μg/ml ；P = 0.007)，IgG2 (1,467 [813-2,607] 对比 1,036 [519-2,012]μg/ml；P = 0.01)，GXM-IgG (1:170 [61-412] 对比 1:117 [47 -176]；P = 0.0009）和较低的凝乳聚糖-IgG（1:47 [11-133] vs. 1:93 [40-206]；P = 0.01）滴度。 GXM-IgG 与隐球菌抗原血症直接相关，根据 CD4 计数和抗逆转录病毒治疗的使用进行调整（比值比，滴度每次对数增加为 1.64；95% 置信区间 [CI]，1.21-2.22）。在 CrAg 阳性个体中，GXM-IgG 与根据 CD4 计数和活动性或流行性结核病调整后的 6 个月死亡率呈负相关（风险比，0.50；滴度每增加对数，减少两倍；95% CI，0.33-0.77） 。 结论 GXM-IgG 与 CrAg 阳性个体死亡率呈负相关的发现表明，GXM-IgG 滴度可能对此类个体具有预后价值。有必要对抗体水平进行前瞻性纵向研究，以调查这一假设并确定抗体可以预防死亡的机制。