Sorbonne Université, INSERM, Centre d'Immunologie et des Maladies Infectieuses (CIMI-Paris), Assistance Publique-Hôpitaux de Paris (AP-HP), Groupement Hospitalier Pitié-Salpêtrière, Département d'Immunologie, Paris, France; Université Paris Diderot Paris 7, Department of Clinical Immunology, Hôpital Saint-Louis, Assistance Publique Hôpitaux de Paris (APHP), Paris, France.
Sorbonne Université, INSERM, Centre d'Immunologie et des Maladies Infectieuses (CIMI-Paris), Assistance Publique-Hôpitaux de Paris (AP-HP), Groupement Hospitalier Pitié-Salpêtrière, Département d'Immunologie, Paris, France.
J Allergy Clin Immunol. 2019 Apr;143(4):1575-1585.e4. doi: 10.1016/j.jaci.2018.09.036. Epub 2018 Dec 13.
Commensals induce local IgA responses essential to the induction of tolerance to gut microbiota, but it remains unclear whether antimicrobiota responses remain confined to the gut.
The aim of this study was to investigate systemic and intestinal responses against the whole microbiota under homeostatic conditions and in the absence of IgA.
We analyzed blood and feces from healthy donors, patients with selective IgA deficiency (SIgAd), and patients with common variable immunodeficiency (CVID). Immunoglobulin-coated bacterial repertoires were analyzed by using combined bacterial fluorescence-activated cell sorting and 16S rRNA sequencing. Bacterial lysates were probed by using Western blot analysis with healthy donor sera.
Although absent from the healthy gut, serum antimicrobiota IgG are present in healthy subjects and increased in patients with SIgAd. IgG converges with nonoverlapping secretory IgA specificities to target the same bacteria. Each individual subject targets a diverse microbiota repertoire with a proportion that correlates inversely with systemic inflammation. Finally, intravenous immunoglobulin preparations target CVID gut microbiota much less efficiently than healthy microbiota.
Secretory IgA and systemic IgG converge to target gut microbiota at the cellular level. SIgAd-associated inflammation is inversely correlated with systemic anticommensal IgG responses, which might serve as a second line of defense. We speculate that patients with SIgAd could benefit from oral IgA supplementation. Our data also suggest that intravenous immunoglobulin preparations can be supplemented with IgG from IgA-deficient patient pools to offer better protection against gut bacterial translocations in patients with CVID.
共生菌诱导局部 IgA 反应对于诱导对肠道微生物群的耐受至关重要，但仍不清楚抗微生物反应是否仍然局限于肠道。
本研究旨在研究在稳态条件下和缺乏 IgA 的情况下，针对整个微生物群的全身和肠道反应。
我们分析了健康供体、选择性 IgA 缺乏症（SIgAd）患者和常见可变免疫缺陷症（CVID）患者的血液和粪便。通过结合细菌荧光激活细胞分选和 16S rRNA 测序分析免疫球蛋白包被的细菌库。使用健康供体血清通过 Western blot 分析探测细菌裂解物。
尽管在健康的肠道中不存在，但健康受试者中存在血清抗微生物 IgG，并且在 SIgAd 患者中增加。IgG 与非重叠的分泌型 IgA 特异性收敛，以靶向相同的细菌。每个个体靶向一个多样化的微生物群 repertoire，其比例与系统炎症呈反比。最后，静脉内免疫球蛋白制剂靶向 CVID 肠道微生物群的效率远低于健康微生物群。
分泌型 IgA 和系统性 IgG 在细胞水平上收敛以靶向肠道微生物群。与 SIgAd 相关的炎症与全身性抗共生 IgG 反应呈负相关，这可能作为第二道防线。我们推测 SIgAd 患者可以从口服 IgA 补充中受益。我们的数据还表明，静脉内免疫球蛋白制剂可以用来自 IgA 缺乏患者群体的 IgG 进行补充，以在 CVID 患者中提供更好的保护，防止肠道细菌易位。
