HLA class II homozygosity confers susceptibility to common variable immunodeficiency (CVID)

Most cases of CVID occur sporadically, but familial cases do also occur and 15% of the patients with the disease have first degree relatives with IgA deficiency (IgAD). Our purpose was to study CVID association with HLA class II alleles and to ascertain whether this disease shares a common genetic b ackground with IgAD in our population. Patients with CVID (n = 42), were ty ped using gene amplification and sequence-specific oligonucleotide probing for HLA-DRB1, DRB3, DQA1 and DQB1 loci and their typing compared with that of 96 IgAD and 334 healthy controls. We observed a positive association bet ween non-Asp residues at position 57 of the HLA-DQ beta chain and CVID, alt hough much weaker than in IgAD. Further, we found an association between CV ID and homozygosity for genes encoding HLA class II molecules, especially H LA-DQ, not seen in IgAD. The data support the hypothesis that a restricted diversity of HLA class II molecules may contribute to susceptibility to CVI D.