Longitudinal study of frequency of HPRT mutant T cells in patients with multiple sclerosis.
Analysis of somatic mutation in circulating peripheral blood T cells can be used as an index of in vivo T-cell amplification. The ability to assess the frequency of T cells that survive in vitro in the presence of 6-thioguanine is an index of mutation at the HPRT gene locus. In the absence of exposure to mutational agents, elevations of the HPRT mutant frequency (mF) of T cells reflects errors in DNA replication and repair that have become fixed during the process of cell division. We estimated the mF of T cells in MS patients and controls over a period of 36 months and found that the mF was consistently elevated in MS patients of all clinical subgroups. In the chronic progressive group of MS, the mF increased over a 3-year period and appeared to correlate with the clinical worsening of the disease.
Sriram
S
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Department of Neurology, Vanderbilt University Medical Center, Nashville, TN 37212.
D000328:Adult; D005260:Female; D006801:Humans; D007041:Hypoxanthine Phosphoribosyltransferase / Q000235:genetics*; D008137:Longitudinal Studies; D008297:Male; D009103:Multiple Sclerosis / Q000201:enzymology* / Q000235:genetics* / Q000503:physiopathology; D009154:Mutation; D009422:Nervous System Diseases / Q000201:enzymology; D012016:Reference Values; D013601:T-Lymphocytes / Q000201:enzymology*; D013866:Thioguanine / Q000032:analysis
D007041:Hypoxanthine Phosphoribosyltransferase; D013866:Thioguanine