Discordance between IgA switching at the DNA level and IgA expression at the mRNA level in IgA-deficient patients

IgA deficiency is a common immune disorder in Caucasians and is associated with certain MHC conserved extended haplotypes, such as [HLA-BS, SC01, DR3] , which presumably carry a susceptibility gene(s). We applied a competitive digestion-circularization PCR method to quantitate the number of switch (S )mu to S alpha rearrangements in peripheral B cells from IgA-deficient subj ects homozygous for this haplotype and compared their number with the produ ctive C alpha mRNA level to determine C alpha gene expression in IgA-switch ed B cells. Two types of defects, low expression of both secreted and membr ane forms of productive C alpha mRNA in IgA-switched B cells and impaired I gA switching, were characterized in IgA-deficient subjects homozygous for [ HLA-B8, SC01, DR3]. The former defect was also found in another noncarrier subject. It may directly cause low IgA secretion and reflects a blockade in post-IgA switch differentiation of B cells. These results suggest that the heterogeneity of defects in IgA deficiency is not simply ascribable to MHC susceptibility genes. (C) 1999 Academic Press.