Familial Clustering of Selective IgA Deficiency

Abstract

Serum IgA levels of 35 healthy IgA-deficient index cases, of their 180 first-degree relatives, and of 31 other family members were studied. IgA deficiency was detected in 7.2% of the first-degree relatives, which is significantly more than the 0.25% frequency of IgA deficiency in healthy Finnish blood donors. Subnormal serum IgA levels were found in additional 13 (7.2%) first-degree relatives. The familial clustering of IgA deficiency seemed to be controlled by multigenic factors. IgA-deficient persons and their family members were tested for antinuclear and antithyroid antibodies, for rheumatoid factor (by latex test) and for other anti-IgG antibodies (by Ripley test). Antibodies against bovine milk were also studied. The relatives of IgA-deficient persons did not have more of these antibodies than the controls. It is suggested that various serological abnormalities are a consequence of the IgA deficiency rather than of genetic defects per se.

The shared CTLA4-ICOS risk locus in celiac disease, IgA deficiency and common variable immunodeficiency

“…Many multicase families show a dominant transmission of the disorder, whereas in other families, it follows autosomal recessive inheritance. 6,7 No primary genetic factor has been identified and variation in familial inheritance patterns suggests that IgAD may be due to multiple genetic defects. Several studies have shown association of HLA alleles with IgAD, [8][9][10][11] and the extended haplotype HLA-A1-B8-DR3 occurs more frequently in individuals with IgAD than it does in the general population.…”

Fine-Scale Mapping at IGAD1 and Genome-Wide Genetic Linkage Analysis Implicate HLA-DQ/DR as a Major Susceptibility Locus in Selective IgA Deficiency and Common Variable Immunodeficiency

“…Oligonucleotide primers and PCR conditions, Mg 2ϩ concentrations, and annealing temperatures are shown as supplemental information or were reported previously (27,28). 4 Allelic sizes, numbers and their frequencies, observed heterozygosity, and polymorphism information content are shown as supplementary information. 4 In addition, genotypes at three cSNPs in the BTLNL2 gene (939A3 G, 1050G3 A, and 1078A3 G), located ϳ20 kb centromeric of LH1 ( Fig.…”

“…4 Allelic sizes, numbers and their frequencies, observed heterozygosity, and polymorphism information content are shown as supplementary information. 4 In addition, genotypes at three cSNPs in the BTLNL2 gene (939A3 G, 1050G3 A, and 1078A3 G), located ϳ20 kb centromeric of LH1 ( Fig. 1) (29), were determined using nucleotide sequencing with BigDye terminators (Applera, Norwalk, CT) as described (26) to establish a telomeric limit of the candidate region on a subset of haplotypes.…”

“…The pedigree structure of each multiplex family is shown as a supplemental information. 4 In addition, we used a control sample of 256 parent-child trios ascertained through Swedish children with cystic fibrosis and phenylketonurea. These trios would not be expected to show a biased segregation at IGAD1 and were used to estimate the relative risk and attributable fraction conferred by the 5-1-7-6 (AH8.1) haplotype.…”

“…Although IgAD/CVID do not show Mendelian segregation in families, they exhibit a high degree of familial clustering (4,5) and marked differences in the population prevalence among ethnic groups, ranging from ϳ1/500 in Caucasians to 1/18500 in Japanese (for review see Ref.…”