Human leukocyte antigen

Disease

Biology

Gene

Endocrinology

Antigen

Allele

Internal medicine

Autoantibody

Immunology

Type 1 diabetes

Genetics

Medicine

Islet

Autoimmune disease

Genetic predisposition

Locus (genetics)

Antibody

Immune tolerance

Pancreatic islets

Immune system

Autoimmunity

Diabetes mellitus

Nature Reviews Endocrinology

Type 1 diabetes mellitus (T1DM) results from the destruction of pancreatic β-cells that is mediated by the immune system. Multiple genetic and environmental factors found in variable combinations in individual patients are involved in the development of T1DM. Genetic risk is defined by the presence of particular allele combinations, which in the major susceptibility locus (the HLA region) affect T cell recognition and tolerance to foreign and autologous molecules. Multiple other loci also regulate and affect features of specific immune responses and modify the vulnerability of β-cells to inflammatory mediators. Compared with the genetic factors, environmental factors that affect the development of T1DM are less well characterized but contact with particular microorganisms is emerging as an important factor. Certain infections might affect immune regulation, and the role of commensal microorganisms, such as the gut microbiota, are important in the education of the developing immune system. Some evidence also s...

The heterogeneous pathogenesis of type 1 diabetes mellitus