One Link Found, Many To Go

Researchers at the UK's Cambridge Institute of Medical Research (CIMR) and Merck & Co. reported a link between cytotoxic T lymphocyte-associated protein 4 (CTLA-4) and autoimmunity (H. Ueda et al., "Association of the T-cell regulatory gene CTLA4 with susceptibility to autoimmune disease," Nature, e-pub ahead of print, doi:10.1038/nature01621, April 30, 2003).

The researchers used positional cloning to search a 330 kb region surrounding the CTLA4 gene for polymorphisms linked to Graves disease, type 1 diabetes, and autoimmune hypothyroidism. The haplotype implicated in all three disorders affected not the amino acid sequence of CTLA-4, which is a negative immune regulator, but rather the relative amounts of mRNA isoforms. The researchers found that the nonobese diabetic mouse phenotype also correlates with an altered ratio of CTLA-4 splice variants. "It points the finger at a form of CTLA-4 that had been recognized before but hadn't been tied...

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