Association among somatic HPRT mutant frequency, peripheral blood T-lymphocyte clonality, and serologic parameters of disease activity in children with juvenile onset dermatomyositis.
Somatic mutant frequencies (Mf) were determined using the HPRT T-cell cloning assay of peripheral blood T-lymphocytes from 14 children with juvenile onset dermatomyositis (JDM). Serologic parameters, specifically muscle enzyme determinations in JDM subjects, were correlated with residual lnMf (delta) in these patients to compare T-cell activation with clinical parameters associated with JDM. In addition TCR analysis was performed to determine T-cell proliferation and clonality on 12 HPRT mutant isolates from two individuals with JDM. Statistically significant correlations were found between residual lnMf and the following serologic parameters: aldolase (r = 0.771, P = 0.015); CPK (r = 0.602, P = 0.023); and SGOT (r = 0.656, P = 0.011) in children with JDM. In addition, identical TCR gene rearrangements were identified in 86 and 40% of the HPRT mutant isolates from the two patient samples analyzed, which is a significantly higher level of clonality than the 10-15% expected in normal individuals. These data suggest that determining HPRT Mf can be a useful antigen-independent method of selecting clonally expanding T-lymphocytes in autoimmune disease where relevant antigens are unknown. Future analysis of HPRT mutant isolates from children with active myositis may increase our understand of the activated T-cells involved in this disease.
Abramson
L S
LS
Department of Pediatrics and Genetic Toxicology Laboratory, University of Vermont, Burlington 05405, USA.
Albertini
R J
RJ
Pachman
L M
LM
Finette
B A
BA
D000293:Adolescent; D017668:Age of Onset; D001219:Aspartate Aminotransferases / Q000097:blood; D002648:Child; D002675:Child, Preschool; D003114:Colony-Forming Units Assay; D003402:Creatine Kinase / Q000097:blood; D003882:Dermatomyositis / Q000201:enzymology / Q000235:genetics* / Q000276:immunology*; D005260:Female; D005634:Fructose-Bisphosphate Aldolase / Q000097:blood; D005787:Gene Frequency; D015333:Gene Rearrangement, beta-Chain T-Cell Antigen Receptor; D006801:Humans; D007041:Hypoxanthine Phosphoribosyltransferase / Q000235:genetics*; D008213:Lymphocyte Activation; D008297:Male; D009154:Mutation; D013601:T-Lymphocytes / Q000276:immunology*
D007041:Hypoxanthine Phosphoribosyltransferase; D001219:Aspartate Aminotransferases; D003402:Creatine Kinase; D005634:Fructose-Bisphosphate Aldolase