Association among SomaticHPRTMutant 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 theHPRTT-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 12HPRTmutant 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 theHPRTmutant 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 determiningHPRTMf can be a useful antigen-independent method of selecting clonally expanding T-lymphocytes in autoimmune disease where relevant antigens are unknown. Future analysis ofHPRTmutant isolates from children with active myositis may increase our understand of the activated T-cells involved in this disease.