Molecular analysis of the IGHA and MHC class III region genes in one family with IgA and C4 deficiencies.

We report molecular studies in 2 IgA-deficient persons. One of them had an unusual association with an acute lymphoblastic leukaemia; his sister was also IgA deficient and shared an HLA haplotype and a complotype known to be associated to IgA deficiencies. The 2 IgA-deficient siblings also had low C4 serum levels due to C4AQ0 allele. We showed that both defects were transmitted independently in the family. Molecular analysis revealed no major structural defects of the IGHA coding and switch regions, whereas a broad C4A-21-OHA deletion was responsible for the C4AQ0 phenotype. These results confirm previous data showing that IgA deficiencies seem to be, in most cases, a regulatory defect rather than a structural defect of the coding IGHA region itself. These data were further supported by another molecular study in a patient with a recurrent Landry-Guillain-Barre syndrome who showed total absence of serum IgA and sIgA+B cells with no major structural defect of the IGHA region.