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 cloni ng assay of peripheral blood T-lymphocytes from 14 children with juvenile o nset dermatomyositis (JDM). Serologic parameters, specifically muscle enzym e determinations in JDM subjects, were correlated with residual lnMf (delta ) in these patients to compare T-cell activation with clinical parameters a ssociated with JDM. In addition TCR analysis was performed to determine T-c ell proliferation and clonality on 12 HPRT mutant isolates from two individ uals with JDM. Statistically significant correlations were found between re sidual 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 ch ildren with JDM. In addition, identical TCR gene rearrangements were identi fied 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 10-1 5% expected in normal individuals. These data suggest that determining HPRT Mf can be a useful antigen-independent method of selecting clonally expand ing T-lymphocytes in autoimmune disease where relevant antigens are unknown . Future analysis of HPRT mutant isolates from children with active myositi s may increase our understand of the activated T-cells involved in this dis ease. (C) 1999 Academic Press.