Systemic antibody responses to gut commensal bacteria during chronic HIV-1 infection
Systemic antibody responses to gut commensal bacteria during chronic HIV-1 infection
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DOI：
10.1136/gut.2010.224774
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发表时间：
2011-11-01
期刊：
影响因子：
24.5
通讯作者：
Oxenius, Annette
中科院分区：
文献类型：
--
作者：
Haas, Anna;Zimmermann, Kathrin;Oxenius, Annette
在健康和疾病期间，人类对共生微生物群的全身抗体反应并没有很好地表征。特别有趣的是分析慢性HIV-1感染引起的它们的潜在调节，慢性HIV-1感染与持续的肠病和系统性B细胞紊乱有关，反映在B细胞反应受损和慢性B细胞过度活跃。B细胞过度活化的机制和由此引起的高γ球蛋白血症的特异性尚不清楚。方法采用活细菌FACS（荧光活化细胞分选）技术，本研究调查了健康供体、慢性hiv -1感染者（伴或不伴腹泻）和炎症性肠病（IBD）患者纵向血浆和血清样本中几种肠道和皮肤共生细菌以及白色念珠菌的全身抗体反应。结果数据显示，对共生菌群的全身抗体反应在人体中大量存在，并且多年来保持显著稳定。在慢性HIV-1感染期间，对肠道共生菌的全身抗体反应不受影响，当HIV患者血浆免疫球蛋白G （IgG）水平升高时，抗体滴度下降。相反，在IBD患者中检测到高亲和力抗菌素抗体的滴度增加，这表明已知的肠通透性增加和异常相互作用的条件可以诱导这些检测中观察到的抗体滴度变化。结论hiv相关性肠病和B细胞功能障碍均不影响对肠道共生菌的高亲和力全身抗体反应。因此，hiv相关的高γ -球蛋白血症不太可能是由抗菌素抗体诱导引起的。
Background Human systemic antibody responses to commensal microbiota are not well characterised during health and disease. Of particular interest is the analysis of their potential modulation caused by chronic HIV-1 infection which is associated with sustained enteropathy and systemic B cell disturbances reflected by impaired B cell responses and chronic B cell hyperactivity. The mechanisms underlying B cell hyperactivation and the specificities of the resulting hypergammaglobulinaemia are only poorly understood.Methods By a technique referred to as live bacterial FACS (fluorescence-activated cell sorting), the present study investigated systemic antibody responses to several gut and skin commensal bacteria as well as Candida albicans in longitudinal plasma and serum samples from healthy donors, chronic HIV-1-infected individuals with or without diarrhoea and patients with inflammatory bowel disease (IBD).Results The data show that systemic antibody responses to the commensal microbiota were abundantly present in humans and remained remarkably stable over years. Overall systemic antibody responses to gut commensal bacteria were not affected during chronic HIV-1 infection, with titres decreasing when normalised to elevated plasma immunoglobulin G (IgG) levels found in patients with HIV. In contrast, increases in the titres of high affinity antimicrobiota antibodies were detected in patients with IBD, demonstrating that conditions with known increased intestinal permeability and aberrant mutualism can induce changes in antibody titres observed in these assays.Conclusion Neither HIV-associated enteropathy nor B cell dysfunction impact on the high-affinity systemic antibody responses to gut commensal bacteria. HIV-associated hypergammaglobulinaemia is therefore unlikely to be driven by induction of antimicrobiota antibodies.