HLA‐DR antigens and phenotypes in Dutch coeliac children and their families

Abstract

In a study on the HLA‐DR antigens and phenotypes in a series of Dutch coeliac children and their first‐degree relatives, the B‐cell antigens of 36 unrelated coeliac children, 110 first‐degree relatives of 33 of them, and 201 controls were typed with the two‐colour fluorescence test. The most frequent antigen was HLA‐DR3 (69%), followed by DR7 (36%). The distribution of DR phenotypes showed that the most frequent was DR3/other DR (25%), followed by DR3/DR7 (17%), DR3/DR4 (14%), and DR3/DR3 (14%). However, due to the frequency of certain antigens in the controls, only phenotypes DR3/DR3 (relative risk = 6.2), DR3/DR7 (relative risk = 6.4), and DR3/DR4 (relative risk = 6.2) were significantly associated with CD. The family study confirmed the segregation of the disease with phenotypes DR3/DR3 and DR3/DR7. The present results show that the association between CD and phenotypes DR3/DR3 and DR3/DR7 is not an exclusive characteristic of Southern coeliac children.

Allelic distribution and the effect of haplotype combination for HLA type II loci in the celiac disease population of the Valencian community (Spain)

“…This latter haplotype is present in almost all the cases (except in 3) associated with DR7-DQ2 or DRB1*11 (serological DR5)-DQA1*0505-DQB1*0301 (35/185; 18.9%), although none of these last alleles, by themselves, present a statistically significant association with CD. This distribution of haplotypes has been previously reported in other Mediterranean countries such as Italy, France or Tunisia where a larger number of CD patients carry the DRB1*07-DQB1*0202-DQA1*0201 haplotype associated with DRB1*11-DQA1*0505-DQB1*0301, compared with North European populations that present a higher number of the DRB1*03-DQB1*0201-DQA1*0501 haplotype (25)(26)(27). Although isolated alleles have no statistical association with CD, haplotype DR4-DQ8 is found in 5.4% of patients (60% together with DQ2) and is the most frequent among the DQ2 negatives.…”

Phenotypic variance in childhood coeliac disease and the HLA-DQ/DR dose effect

“…The strong relationship between HLA genetic factors and CD is illustrated by the impact of the HLA-DQ2 gene dose on the chance of disease development: HLA-DQ2 homozygous individuals have an at least five times higher risk of disease development compared with HLA-DQ2 heterozygous individuals [21,22]. In addition, the gene dosage is determined by the amount of expressed HLA-DQ2/DQ8 in the small intestine, caused by the combination of the ab chains of the DQ2 (A1*0501, B1*0201 or A1*0201, B1*0202) and DQ8 (A1*0301, B1*0302) heterodimers.…”

Prevalence of Genetic Susceptibility for Celiac Disease in Blood Donors in São Paulo, Brazil

“…The 12th tube of the reaction identifies the DQB1*02 allele in homozygous, which is an important information, because studies reveal that homozygous haplotype, increases patient´s susceptibility to develop CD (17,21,22) .…”