HLA Antigens and Phenotypes Associated with Severe Immunoglobulin — a Deficiency in Coeliac Disease Paediatric Patients

Class I and II HLA antigens were determined by a standard microlymphocyto-toxicity test in 45 paediatric patients with severe Immunoglobulin A deficiency (serum levels of IgA <5mg/d1) and in all first degree relatives of eighteen of them. IgG and IgM serum levels were normal in almost all patients and in all members of the families. This study included two subgroups of IgA deficient (IgA-d) patients: one (CD) composed by 12 coeliac patients (8 girls and 4 boys, mean age at the time of diagnosis (DMA: 3.3) and the other (RTIAG) of 33 patients (22 boys and 11 girls, DMA: 5.7) with frequent respiratory tract infections, allergic diseases or gastrointestinal disorders. It was found that the HLA antigens associated with IgA deficiency were different from one subgroup to the other. When HLA antigen fre-quencies in IgA-d coeliac patients were compared with those present in 51 CD children with normal serum levels of IgA, the frequency of B14 was found to be significantly increased among IgA-d (36.4% vs 7.8%, p=4.0x10−2) and resulted in an elevated relative risk: RR=6.71 and etiological fraction: EF=0.31. Among RTIAG patients: the frequency of DR1 antigen was significantly raised when compared with those of 166 healthy local donors (63.3%, p=2.1x10−4, RR=5.47, EF=0.52). Frequencies of phenotypes: DR1,DR3; B35,DR1; A28,B14,DR1 were also increased with RR of 7.01; 4.96 and 11.10 respectively. Despite the differences found, similarities were observed between both groups of patients: the increasing fre-quencies of shared phenotypes Al,B8,DR3 and DR1, DR3 and the negative associa-tion of DR2 and DR4 antigens. These findings strongly suggest that HLA region gene(s) may be involved in the susceptibility of IgA deficiency and allele of different loci could be related according to the type of associated disease. We conclude that the presence of B14 could increase the risk in coeliac disease and DR1 could play a similar role in patients with respiratory, allergic or gastrointestinal pathologies.