T cell numbers relate to bone involvement in Gaucher disease

The major elements of bone pathology in Gaucher disease are a failure of os teoclast and osteoblast function, resulting in osteopenia and also osteonec rosis. T lymphocytes have recently been found to be involved in the regulat ion of osteoblast/osteoclast activity in vitro. In the present report the p eripheral blood T major lymphocyte subsets were investigated in a group of genotyped type 1 Gaucher disease patients, A total of 31 patients were stud ied: 21 non-splenectomized (5 N370S homozygotes) and 10 splenectomized (of whom 1 was a N370S homozygote). The results show that non-splenectomized pa tients present a decrease in absolute numbers of peripheral blood T lymphoc ytes, specially the CD4(+) T subset. However, when patients were analyzed w ith respect to the presence of bone disease, the number of CD8(+) T lymphoc ytes was found to be statistically significantly lower in patients presenti ng bone involvement. Furthermore, lower numbers of CD8(+) T lymphocytes wer e significantly correlated with higher levels of plasma tartrate resistant acid phosphatase (TRAP) activity, a putative marker of osteoclast cell acti vity. These in vivo findings are in agreement with the results reached in v itro by others. They provide an additional marker of disease severity in Ga ucher disease. In the group of genotyped Gaucher disease patients, the majo rity of the N370S homozygous patients presented a clinically milder phenoty pe, including the absence of bone involvement, confirming earlier reports p redicting that a number of these patients may remain undiagnosed. Collectiv ely the homozygosity for the N370S mutation and normal T cell numbers may p rovide additional markers for the clinical heterogeneity of Gaucher disease . (C) 1999 Academic Press.