Multiple myeloma patients in long-term complete response after autologous stem cell transplantation express a particular immune signature with potential prognostic implication.

The proportion of multiple myeloma patients in long-term complete response (LTCR-MM) for more than 6 years after autologous stem cell transplantation (ASCT) is small. To evaluate whether this LTCR is associated with a particular immune signature, peripheral blood samples from 13 LTCR-MM after ASCT and healthy blood donors (HBD) were analysed. Subpopulations of T-cells (naïve, effector, central memory and regulatory), B-cells (naïve, marginal zone-like, class-switched memory, transitional and plasmablasts) and NK-cells expressing inhibitory and activating receptors were quantified by multiparametric flow cytometry (MFC). Heavy/light chains (HLC) were quantified by nephelometry. The percentage of CD4+ T-cells was lower in patients, whereas an increment in the percentage of CD4+ and CD8+ effector memory T-cells was associated with the LTCR. Regulatory T-cells and NK-cells were similar in both groups but a particular redistribution of inhibitory and activating receptors in NK-cells were found in patients. Regarding B-cells, an increase in naïve cells and a corresponding reduction in marginal zone-like and class-switched memory B-cells was observed. The HLC values were normal. Our results suggest that LTCR-MM patients express a particular immune signature, which probably reflects a 'high quality' immune reconstitution that could exert a competent anti-tumor immunological surveillance along with a recovery of the humoral immunity.

B lymphopenia in uremia is related to an accelerated in vitro apoptosis and dysregulation of Bcl-2.

BACKGROUND: Lymphopenia has been described in patients with chronic renal failure (CRF). It is postulated that the decline in lymphocytes is due to accelerated apoptosis. We investigated whether dysregulation of programmed cell death plays a role in the immunodeficiency described in CRF. METHODS: Peripheral blood lymphocytes (PBL) from pre-dialysis uraemic patients (nHD) and haemodialysed patients (HD) were cultured with no stimulus for 96 h. Apoptosis of lymphocytes was measured by propidium iodide staining and flow cytometry. Expression of Fas and Bcl-2 was also analysed by flow cytometry. RESULTS: Peripheral blood B cells were significantly lower in pre-dialysis and haemodialysis uraemic patients compared to control. Lymphocytes from both groups of patients had a higher rate of apoptosis in vitro than those from healthy controls. This effect was more pronounced in B lymphocytes and a significant correlation between the B lymphopenia and the percentage of apoptotic B cells after 48 h of culture without stimulus was observed. The increased lymphocyte apoptosis in CRF was accompanied by a significantly lower in vitro Bcl-2 expression. However, Fas did not seem to play a role in spontaneous lymphocyte apoptosis in end-stage renal disease. CONCLUSIONS: Our data indicate that B lymphopenia in CRF may be partially attributed to an increased susceptibility to cell death by apoptosis that is associated with a decreased expression of Bcl-2.