AUTOIMMUNITY

Prog Retin Eye Res. 2018 Jul;65:107-126. doi: 10.1016/j.preteyeres.2018.02.003. Epub 2018 Feb 27. Research Support, Non-U.S. Gov't; Review

Specialized immune cell subsets are involved in autoimmune disease, cancer immunity, and infectious disease through a diverse range of functions mediated by overlapping pathways and signals. However, subset-specific responses may not be detectable in analyses of whole blood samples, and no efficient approach for profiling cell subsets at high throughput from small samples is available. We present a low-input microfluidic system for sorting immune cells into subsets and profiling their gene expression. We validate the system’s technical performance against standard subset isolation and library construction protocols and demonstrate the importance of subset-specific profiling through in vitro stimulation experiments. We show the ability of this integrated platform to identify subset-specific disease signatures by profiling four immune cell subsets in blood from patients with systemic lupus erythematosus (SLE) and matched control subjects. The platform has the potential to make multiplexed subset-specific analysis routine in many research laboratories and clinical settings.

HLA haplotypes in conjunction with serum anticommensal antibody responses are predictive of type 1 diabetes progression. See related Research Article by [Paun et al .][1]

[1]: http://immunology.sciencemag.org/content/4/32/eaau8125.full

Research Highlight

Studies in humans and mice have identified associations between intestinal microbiome composition and development of autoimmune diseases, including type 1 diabetes (T1D). How these microbes exert influence on immune responses in distant tissues is unknown. By studying pediatric cohorts, Paun et al. examined whether serum antibody responses to intestinal commensal bacteria were associated with T1D status. They report that antibody responses against specific commensals measured before T1D diagnosis distinguished individuals with islet autoantibodies from healthy controls in a human leukocyte antigen haplotype–dependent manner. Their results link immune responses to gut microbes with later T1D development and suggest that they may be predictive of T1D when analyzed with genetic risk factors.

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.

The immune system normally defends the body against everything from microscopic viruses to meters-long parasitic worms. But sometimes, it sets its sights on the wrong target: the body's own cells.

Studies in humans and mice have identified associations between intestinal microbiome composition and development of autoimmune diseases, including type 1 diabetes (T1D). How these microbes exert influence on immune responses in distant tissues is unknown. By studying pediatric cohorts, Paun et al. examined whether serum antibody responses to intestinal commensal bacteria were associated with T1D status. They report that antibody responses against specific commensals measured before T1D diagnosis distinguished individuals with islet autoantibodies from healthy controls in a human leukocyte antigen haplotype–dependent manner. Their results link immune responses to gut microbes with later T1D development and suggest that they may be predictive of T1D when analyzed with genetic risk factors.

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.