Celiac and Endocrine Autoimmune Disorders in Children
Celiac and Endocrine Autoimmune Disorders in Children
The genetic basis of CD is traditionally split into variants within the Human Leukocyte Antigen (HLA) region and non-HLA variants. HLA heterodimer DQ2 is present in 95% of CD patients, whereas 5–10% carries the DQ8 heterodimer. HLA-DQ2 and HLA-DQ8 were considered the strongest genetic risk factors for CD; however, genome-wide association studies continue to link CD with non-HLA gene variants that control immune response, particularly B- and T-cell function.
Interestingly, many of the susceptibility loci for CD are shared with those for AI with a substantial genetic overlap. The HLA DR3-DQ2 and DR4-DQ8 haplotypes are indeed common in many AI. The genotype DR3-DQ2/DR4-DQ8 is associated with the highest risk of developing Type 1 diabetes but also with thyroid autoimmunity (TA) and Addison's disease (AD). These results underline the important common genetic background of these conditions and suggest that there may be a shared genetic contribution. The common background is modified by a further subset of disease-specific genes and environmental insults leading to either T1D or CD or other AI.
Genetic Aspects
The genetic basis of CD is traditionally split into variants within the Human Leukocyte Antigen (HLA) region and non-HLA variants. HLA heterodimer DQ2 is present in 95% of CD patients, whereas 5–10% carries the DQ8 heterodimer. HLA-DQ2 and HLA-DQ8 were considered the strongest genetic risk factors for CD; however, genome-wide association studies continue to link CD with non-HLA gene variants that control immune response, particularly B- and T-cell function.
Interestingly, many of the susceptibility loci for CD are shared with those for AI with a substantial genetic overlap. The HLA DR3-DQ2 and DR4-DQ8 haplotypes are indeed common in many AI. The genotype DR3-DQ2/DR4-DQ8 is associated with the highest risk of developing Type 1 diabetes but also with thyroid autoimmunity (TA) and Addison's disease (AD). These results underline the important common genetic background of these conditions and suggest that there may be a shared genetic contribution. The common background is modified by a further subset of disease-specific genes and environmental insults leading to either T1D or CD or other AI.