Science子刊:对共生菌的抗体应答与儿童1型糖尿病相关,且受HLA影响
创作:沈志勋 审核:沈志勋 02月11日
  • 纳入32名克罗恩病(CD)患儿、90名健康儿童、49名1型糖尿病(T1D)患儿;
  • 3组儿童的血清抗共生菌群抗体(ACAb)应答之间存在显著差异;
  • 分析诊断出T1D之前的ACAb是否与随后的T1D疾病发展相关;
  • 针对Roseburia faecis及一系列特定细菌的血清IgG2b抗体与随后的T1D诊断相关,而这种相关性依赖于HLA DR3/DR4单体型;
  • 针对特定共生细菌的ACAb应答与胰岛自身免疫反应相关,这种相关性同样受到HLA-DR单体型的影响。
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Science Immunology [IF:10.551]

Association of HLA-dependent islet autoimmunity with systemic antibody responses to intestinal commensal bacteria in children

儿童中,依赖于HLA的胰岛自身免疫与对肠道共生菌的系统性抗体应答相关

10.1126/sciimmunol.aau8125

02-01, Article

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Abstract:收起
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 (T1D) 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 T1D 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 T1D 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 T1D. 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.

First Authors:
Alexandra Paun,Christopher Yau

Correspondence Authors:
Alexandra Paun,Christopher Yau,Jayne S Danska

All Authors:
Alexandra Paun,Christopher Yau,Shahab Meshkibaf,Michelle C Daigneault,Leili Marandi,Steven Mortin-Toth,Amit Bar-Or,Emma Allen-Vercoe,Philippe Poussier,Jayne S Danska

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