HLA-B8,DR3 HAPLOTYPE AFFECTS LYMPHOCYTE BLOOD-LEVELS

The number of lymphocytes in the blood is constant, pointing to an eff ective control of circulating lymphocyte values. The mechanisms of thi s regulation are uncertain, although it is likely that the number of b lood lymphocytes is conditioned by hormones, homing factors and cytoki nes whose production is at least partly restrained by genetic factors. Particularly genetic factors linked to major histocompatibility compl ex (MHC) appear to be involved. In human beings a decreased number of blood lymphocytes has been described in healthy subjects carrying the Human Leucocyte Antigens (HLA) haplotype HLA-B8,DR3. In the present st udy, to enquire into the mechanisms of this lymphocyte decreased numbe r, we have performed an analysis of blood subset values in these subje cts. When the absolute values of lymphocytes were analysed according t o HLA phenotype, HLA-B8,DR3 positive subjects (N=26) displayed signifi cantly lower values as compared to HLA-B8,DR3 negative ones (N=282). T he analysis of lymphocyte subpopulations performed by flow cytometry i n 72 subjects did not show significant changes in lymphocyte subset pe rcentages between HLA-B8,DR3 positive subjects and negative ones. Thus , the decrease of circulating lymphocytes seems to be due to a reducti on of cell number affecting all lymphocyte subsets rather than a singl e cell subpopulation. The analysys of in vitro spontaneous apoptosis p erformed by now cytometry in a smaller sample of subjects showed a sig nificant increase of spontaneous apoptosis in lymphocytes from HLA-B8, DR3 positive individuals suggesting a possible explanation for the dev iation from normal lymphocyte count observed in these subjects. Howeve r it is intriguing that a decreased number of blood lymphocytes can be observed in healthy HLA-B8,DR3 positive subjects but also in autoimmu ne diseases linked to this haplotype like systemic lupus erythematosus and insulin-dependent diabetes. Furthermore, in our opininon, this fi nding is to be kept in mind in evaluating hematological parameters in healthy subjects.