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.
Fernández-Fresnedo
G
G
Nephrology and Immunology Units, Hospital Universitario Marqués de Valdecilla, INSALUD, Santander, Spain.
Ramos
M A
MA
González-Pardo
M C
MC
de Francisco
A L
AL
López-Hoyos
M
M
Arias
M
M
D000293:Adolescent; D000328:Adult; D000368:Aged; D017209:Apoptosis; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D015415:Biomarkers; D002478:Cells, Cultured; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007676:Kidney Failure, Chronic / Q000097:blood* / Q000150:complications / Q000473:pathology / Q000628:therapy; D018655:Lymphocyte Count; D008231:Lymphopenia / Q000097:blood* / Q000209:etiology / Q000473:pathology; D008297:Male; D008875:Middle Aged; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism*; D006435:Renal Dialysis; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D014511:Uremia / Q000097:blood* / Q000150:complications / Q000473:pathology / Q000628:therapy; D019014:fas Receptor / Q000378:metabolism
D015415:Biomarkers; D019253:Proto-Oncogene Proteins c-bcl-2; D019014:fas Receptor