Leukocyte proliferation and immune modulator production in patients with chronic kidney disease.
BACKGROUND
In Chronic Kidney Disease (CKD), immune cells are affected by uremic retention toxins. Given this effect, we analyzed lymphocyte proliferative response and immune modulators production following in vitro stimulation.


METHODS
Whole blood was drawn from healthy controls, patients with eGFR <20 ml/min/1.73 m(2) (Pre-dialysis, CKD stages 4 and 5) and hemodialysis patients (stage 5D). Peripheral cells were incubated for six days with pokeweed mitogen, concanavalin A, Staphylococcus enterotoxin A or influenza A vaccine. Peripheral lymphocyte proliferation was then analyzed by the "Flow-cytometric Assay of Specific Cell-mediated Immune response in Activated whole blood" (FASCIA) method, and cytokine profile in the cell supernatants was analyzed by the Milliplex multi-array method.


RESULTS
The absolute number of lymphoblasts in response to mitogenic stimulation and the number of cells in each CD4+ and CD8+ subpopulation were similar comparing the three groups, except for a single decline in number of lymphoblasts after stimulation with Staphylococcus enterotoxin A, comparing dialysis patients with healthy controls. Levels of interleukin (IL)-2 (p=0.026), -10 (p=0.019) and -15 (p=0.027) in the Staphylococcus enterotoxin A-stimulated supernatant were lower in hemodialysis patients compared to healthy controls. Levels of IL-15 (p=0.017) from pre-dialysis patients and levels of IL-5 (p=0.019) from hemodialysis patients in influenza A vaccine-stimulated supernatants were also lower compared to controls. In pokeweed mitogen-stimulated supernatant, IL-2 levels (p=0.013) were lower in hemodialysis patients compared to pre-dialysis patients. TNF-α, IL-10, IL-12, IL-15, IL-8, MCP-1, IP-10, IFN-α2, IL-1α and eotaxin levels were all significantly higher in plasma obtained from CKD patients.


CONCLUSIONS
Our results suggest that T-cells from CKD patients have similar proliferative response to stimulation compared with healthy individuals. Moreover, however the immune cells show inability to produce selected cytokines, most likely due to the uremic milieu or dialysis procedure.
Unit of Clinical Immunology and Allergy, Department of Medicine, Karolinska University Hospital Solna, Karolinska Institutet, Stockholm, Sweden. ladan.mansouri@ki.se
Ladan
L
Mansouri
Josefin M
JM
Paulsson
Ali
A
Moshfegh
Stefan H
SH
Jacobson
Joachim
J
Lundahl
D000328:Adult; D000368:Aged; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology* / Q000473:pathology; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology* / Q000473:pathology; D016022:Case-Control Studies; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D003208:Concanavalin A / Q000494:pharmacology; D016207:Cytokines / Q000096:biosynthesis / Q000276:immunology*; D004768:Enterotoxins / Q000494:pharmacology; D005260:Female; D005919:Glomerular Filtration Rate; D006801:Humans; D007252:Influenza Vaccines / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D008934:Mitogens / Q000494:pharmacology; D011043:Pokeweed Mitogens / Q000494:pharmacology; D006435:Renal Dialysis; D051436:Renal Insufficiency, Chronic / Q000276:immunology* / Q000378:metabolism / Q000473:pathology
D016207:Cytokines; D004768:Enterotoxins; D007252:Influenza Vaccines; D008934:Mitogens; D011043:Pokeweed Mitogens; D003208:Concanavalin A; C026066:enterotoxin A, Staphylococcal