Genetic Association in Familial Common Variable Immunodeficiency (CVID) and IgA Deficiency (IgAD)

Common variable immunodeficiency (CVID) is a heterogeneous syndrome described by defective antibody production and occurrence of multiple clinical manifestations including autoimmune, lymphoproliferative, and granulomatous diseases. Genes within the major histocompatibility complex (MHC) region have previously been reported to be involved in the pathogenesis of the disease.

To elucidate the human leukocyte antigen (HLA) association, PCR was performed to clarify type HLA B, DR, and DQ alleles in a large sample of Iranian and Swedish CVID patients.

No HLA association was observed between Iranian patients with “sporadic” CVID (n=50) and controls. A slight HLA association (B8, DR3, DQ2) was found in Swedish CVID patients (n=95). However, the latter was entirely due to an association in the familial form of the disease. Using 13 informative multiplex families with patients affected by CVID and IgA deficiency (IgAD), shared haplotypes such as HLA-B8-DR3-DQ2; HLA-DR1-DQ5; HLA- DR4- DQ3, and HLA-DR7-DQ2 were observed.

Based on our results, we hypothesize that only the familial form of CVID/IgAD may have a common HLA-associated genetic background, whereas “sporadic” cases show no HLA association.