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Defective Gene Linked to Two Inherited Immune Deficiencies

cific role in orchestrating the immune response. Defects in TACI were found in 4 of 19 unrelated patients with CVID and in 1 of 16 unrelated patients with IgA deficiency. None of 50 healthy people they studied had a TACI mutation. The scientists believe that it is likely that as yet unidentified genetic defects underlie CVID and IgA deficiency in those cases where TACI was not mutated.

When the scientists further examined four of the five individuals with TACI mutations, they found all four had relatives with the same mutations. Eleven of the 12 identified relatives with CVID or IgA deficiency reported a history of recurrent infections and were also found to have low levels of IgA and/or low levels of another type of antibody, immunoglobulin G (IgG).

TACI mutations interfere with two aspects of the immune response that involve maturation of B cells. Normally, TACI triggers B cells to switch from making immunoglobulin M (IgM), an antibody produced early in the immune response, to making other antibodies such as IgA and IgG. More important, TACI signals B cells to produce antibodies against specific invading bacteria and viruses.

Because TACI mutations are genetically dominant, a person with TACI mutations in one of the two TACI genes he or she inherits is unable to mount a strong antibody response. Each child of a person so affected has a 50 percent chance of inheriting the mutation and being predisposed to IgA deficiency and CVID.

“A test for TACI defects would enable the diagnosis of more children and their relatives with these immune deficiencies,?says Dr. Geha, senior author of the study and the James Gamble Professor of Pediatrics at Harvard Medical School. “Many children who are sick with these disorders are now missed, because they can have normal IgA and IgG levels, yet they still have poor antibody responses and get the same bacterial and virus infections again and again.?/p>

But the gene discovery will not immediately cha
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Source:NIH


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