Mutations in TACI were also found in relatives of patients with CVID who suffered from IgA deficiency (IgAD) as well as in a patient with isolated IgAD.
Common variable immunodeficiency, CVID, is a primary antibody deficiency characterized by decreased levels of serum immunoglobulin G (IgG), decreased IgA and/or IgM and recurrent infections.
Recently, patients with CVID and IGAD have been found to have mutations of the gene TNFRSF13B encoding the TACI (transmembrane activator and calcium-modulator and cyclophilin-ligand interactor), a member of the tumor necrosis factor-receptor superfamily.
A relative predispositional effect (RPE) study showed that in addition to the primary positive association of IgAD with HLA-DRB1*0102, DR3/TNFa2b3, and DR7 carrying haplotypes, DRB1*1501 was a marker of a primary protective factor in the Spanish population.
Our results indicate that the gene frequency of the DRB1*0102 subtype and of the DRB1*0102, DQB1*0501 haplotype is significantly higher in IgA-D than in the general population.
As expected, the risk-conveying HLA alleles A*01, B*08 and DRB1*01 were overrepresented among the IgAD twins and were also associated with significantly lower mean serum IgA concentrations in the twin cohort.
Our results indicate that the gene frequency of the DRB1*0102 subtype and of the DRB1*0102, DQB1*0501 haplotype is significantly higher in IgA-D than in the general population.
As expected, the risk-conveying HLA alleles A*01, B*08 and DRB1*01 were overrepresented among the IgAD twins and were also associated with significantly lower mean serum IgA concentrations in the twin cohort.
A relative predispositional effect (RPE) study showed that in addition to the primary positive association of IgAD with HLA-DRB1*0102, DR3/TNFa2b3, and DR7 carrying haplotypes, DRB1*1501 was a marker of a primary protective factor in the Spanish population.
On day 0, the IgA+ patient expressed interleukin (IL)-4 and IL-10, but not IL-2, IFN-gamma, or IL-6 mRNA; the IgA- patient expressed IL-6 and IL-10 mRNA, but not IL-4, IL-2, or IFN-gamma mRNA.
IgA-D subjects homozygous for HLA DQB1*0201 (DQw2), a marker that has previously been reported to show a strong association with IgA deficiency, showed a similar reduction of serum levels of IgG4 and IgE as compared with DQB1*0201 negative IgA-D subjects.
Similar to the mice, Ig S joints from CVID and IgA deficiency patients carrying disease-associated MSH5 alleles show increased donor/acceptor microhomology, involving pentameric DNA repeat sequences and lower mutation rates than controls.
Preliminary evidences demonstrating that low amounts of human recombinant IL-5 are able to reconstitute IgA production by cells from HLA-B8, DR3 IgA-D subjects, seem to confirm this hypothesis.