Association of HLA-dependent islet autoimmunity with systemic antibody responses to intestinal commensal bacteria in children
Association of HLA-dependent islet autoimmunity with systemic antibody responses to intestinal commensal bacteria in children
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DOI：
10.1126/sciimmunol.aau8125
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发表时间：
2019-02-01
影响因子：
24.8
通讯作者：
Danska, Jayne S.
中科院分区：
文献类型：
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作者：
Paun, Alexandra;Yau, Christopher;Danska, Jayne S.
微生物组序列分析表明，肠道细菌组成的变化与人类和动物模型中的自身免疫性疾病有关。然而，人们对肠道微生物群影响对远端组织的自身免疫反应的机制知之甚少。在这里，我们评估了针对培养的人肠道细菌菌株的全身抗体应答，以确定在两组儿科研究参与者中观察到的抗人源性抗体（ACAb）应答模式是否与1型糖尿病（T1 D）相关。在第一个队列中，将从T1 D诊断6个月内的参与者收集的血清中的ACAb反应与年龄匹配的健康对照以及近期发作的克罗恩病患者进行比较。ACAb对多种细菌的反应在这三组中有区别。在第二组中，我们询问诊断前存在的ACAb应答是否与随后的T1 D发展相关，以及与随后进展为糖尿病的参与者中的HLA基因型相关。针对Roseburia faecis和针对细菌聚生体的血清IgG 2抗体以HLA DR 3/DR 4单倍型依赖性方式与未来的TlD诊断相关。这些分析揭示了对肠道微生物的抗体应答与HLA-DR基因型和胰岛自身抗体特异性之间的关联以及与T1 D的未来诊断之间的关联。此外，我们提出了一个平台，以调查抗菌抗体的生物液体，适用于自身免疫性疾病的研究和治疗干预的反应。
Microbiome sequence analyses have suggested that changes in gut bacterial composition are associated with autoimmune disease in humans and animal models. However, little is known of the mechanisms through which the gut microbiota influences autoimmune responses to distant tissues. Here, we evaluated systemic antibody responses against cultured human gut bacterial strains to determine whether observed patterns of anticommensal antibody (ACAb) responses are associated with type 1 diabetes (T1 D) in two cohorts of pediatric study participants. In the first cohort, ACAb responses in sera collected from participants within 6 months of T1D diagnosis were compared with age-matched healthy controls and also with patients with recent onset Crohn's disease. ACAb responses against multiple bacterial species discriminated among these three groups. In the second cohort, we asked whether ACAb responses present before diagnosis were associated with later T1 D development and with HLA genotype in participants who were discordant for subsequent progression to diabetes. Serum IgG2 antibodies against Roseburia faecis and against a bacterial consortium were associated with future T1 D diagnosis in an HLA DR3/DR4 haplotype-dependent manner. These analyses reveal associations between antibody responses to intestinal microbes and HLA-DR genotype and islet autoantibody specificity and with a future diagnosis of T1 D. Further, we present a platform to investigate antibacterial antibodies in biological fluids that is applicable to studies of autoimmune diseases and responses to therapeutic interventions.