Restoring tolerance to β-cells in Type 1 diabetes: Current and emerging strategies

Carroll, Kaitlin; Katz, Jonathan D.

doi:10.1016/j.cellimm.2022.104593

Cited by 2 publications

(1 citation statement)

References 60 publications

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“…While Tregs can have a suppressive effect on autoreactive T cells and prevent the development of autoimmune diseases, they may also exhibit functional defects in AD patients ( 53 ). These defects might limit their ability to effectively control immune responses, ultimately leading to the activation of autoreactive T cells that target pancreatic beta cells and contribute to the development of T1D ( 54 , 55 ). In addition, heightened production of pro-inflammatory cytokines generated by Th17 cells has demonstrated a positive correlation with the emergence of type 1 diabetes (T1D) ( 56 , 57 ).…”

Section: Discussionmentioning

confidence: 99%

Association of atopic dermatitis with autoimmune diseases: A bidirectional and multivariable two-sample mendelian randomization study

Zhou

Cai

et al. 2023

Front. Immunol.

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BackgroundObservational studies have suggested the association between atopic dermatitis (AD) and the risks of autoimmune diseases. It is still unclear, however, whether or in which direction causal relationships exist, because these associations could be confounded.ObjectivesOur study seeks to assess the possibility of AD as a cause of autoimmune diseases, and to estimate the magnitude of the causal effect.MethodsTwo-sample mendelian randomization (MR) analyses were performed using genome-wide association study (GWAS) summary-level statistics. Specifically, bidirectional MR analyses were conducted to examine the direction of association of AD with autoimmune diseases; multivariable MR analyses (MVMR1) were used to test the independence of causal association of AD with autoimmune diseases after controlling other atopic disorders (asthma and allergic rhinitis), while MVMR2 analyses were conducted to account for potential confounding factors such as smoking, drinking, and obesity. Genetic instruments for AD (Ncases=22 474) were from the latest GWAS meta-analysis. The GWAS summary data for asthma and allergic rhinitis were obtained from UK Biobank. The GWAS summary data for smoking, alcohol consumption, obesity and autoimmune diseases (alopecia areata, vitiligo, systemic lupus erythematosus, ankylosing spondylitis, rheumatoid arthritis, and type 1 diabetes) were selected from the largest GWASs available. Causal estimates were derived by the inverse-variance weighted method and verified through a series of sensitivity analyses.ResultsGenetically predicted AD linked to higher risks of rheumatoid arthritis (OR, 1.28; P=0.0068) (ORMVMR1, 1.65; P=0.0020) (ORMVMR2, 1.36; P<0.001), type 1 diabetes (OR, 1.37; P=0.0084) (ORMVMR1, 1.42; P=0.0155) (ORMVMR2, 1.45; P=0.002), and alopecia areata (OR, 1.98; P=0.0059) (ORMVMR1, 2.55; P<0.001) (ORMVMR2, 1.99; P=0.003) in both univariable and multivariable MR. These causal relationships were supported by sensitivity analyses. No causal effect of AD was identified in relation to systemic lupus erythematosus, vitiligo, and ankylosing spondylitis. Concerning the reverse directions, no significant association was noted.ConclusionThe results of this MR study provide evidence to support the idea that AD causes a greater risk of rheumatoid arthritis, type 1 diabetes and alopecia areata. Further replication in larger samples is needed to validate our findings, and experimental studies are needed to explore the underlying mechanisms of these causal effects.

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Section: Discussionmentioning

confidence: 99%

Association of atopic dermatitis with autoimmune diseases: A bidirectional and multivariable two-sample mendelian randomization study

Zhou

Cai

et al. 2023

Front. Immunol.

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Autologous hematopoietic stem cell transplantation as a method of immune prevention of type 1 diabetes mellitus: possibilities and prospects

Chernaya,

Khalimov,

Volkova

et al. 2024

Diabetes mellitus

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Type 1 diabetes mellitus (DM) is one of the most common autoimmune disease that is treated with lifelong insulin therapy. Non-target indicators of glycemic control, which are observed in 71% of patients, lead to the formation and progression of diabetes complications, early disability and mortality. In this regard, the search for new approaches to the treatment and prevention of type 1 DM seems to be relevant. Various methods of immunological prophylaxis for the development of type 1 DM have been studied, in particular, the use of monoclonal antibodies. Thus, in November 2022, teplizumab was approved to slow down the clinical progression of the stage of type 1 DM. The prospects for the use of new options for islet cell transplantation are being studied — in June 2023, an allogeneic donor β-cell transplant obtained from the pancreas of donors after death was approved. Another pathogenetically substantiated method for the prevention and treatment of autoimmune diseases is high-dose immunosuppressive therapy with autologous hematopoietic stem cell transplantation (HDIT-HSCT). HDIT-HSCT demonstrated its effectiveness and cost-effectiveness in various clinical trials. This review provides up-to-date information on modern methods of immunological prophylaxis of type 1 DM.

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Restoring tolerance to β-cells in Type 1 diabetes: Current and emerging strategies

Cited by 2 publications

References 60 publications

Association of atopic dermatitis with autoimmune diseases: A bidirectional and multivariable two-sample mendelian randomization study

Association of atopic dermatitis with autoimmune diseases: A bidirectional and multivariable two-sample mendelian randomization study

Autologous hematopoietic stem cell transplantation as a method of immune prevention of type 1 diabetes mellitus: possibilities and prospects

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