Natural killer cell alterations correlate with loss of renal function and dialysis duration in uraemic patients.
BACKGROUND
Natural killer (NK) cells provide a first line of immune defence towards infections and tumours, and participate in atherosclerosis and pregnancy diseases, of which there is a higher incidence in uraemic patients. Still, their relative contribution to the immunodeficient state associated with renal failure is poorly documented.


METHODS
A multivariate and comparative analysis of lymphocyte subsets in haemodialysed (HD) and undialysed (UD) uraemic patients in comparison to healthy donors (HC) is provided in this article. NK-mediated cytotoxicity, degranulation and interferon secretion were compared in HD and HC.


RESULTS
Evaluation of NK cells in 210 HD patients concluded with a decrease in NK cell counts in comparison to HC. Multivariate analysis associated lowered NK cell counts in UD patients with decreased renal clearance and higher NK counts HD with male gender and age. The 32% NK cell count decrease observed in sex- and age-matched groups (n = 88) was associated with B- and CD8(+)T-lymphocyte defects. NK cell functions were similar in subgroups of HD and HC matched for NK cell counts. Longer dialysis duration was associated with improved NK cytototoxic activity. While the expression of receptors modulating NK cytotoxicity were not modified, expression of the activation markers CD69 and NKp44, CD94 and chemokine receptors CX3CR1 and CXCR4 was altered in HD.


CONCLUSIONS
This study is the first to associate decrease in renal function with selective fading of NK cell number and identify haemodialysis duration as a factor influencing NK cell function. It further shows that lower cell counts rather than intrinsic NK cell dysfunction per se characterize immune disorders in HD.
Vacher-Coponat
Henri
H
Laboratoire Hématologie Cellulaire Spécialisée, Hematology unit, Hopital de la Conception, 147 bd Baille, 13005 Marseille, France.
Brunet
Corinne
C
Lyonnet
Luc
L
Bonnet
Elodie
E
Loundou
Andersen
A
Sampol
José
J
Moal
Valérie
V
Dussol
Bertrand
B
Brunet
Philippe
P
Berland
Yvon
Y
Dignat-George
Françoise
F
Paul
Pascale
P
D015703:Antigens, CD / Q000096:biosynthesis / Q000276:immunology; D018941:Antigens, CD19 / Q000276:immunology; D000945:Antigens, Differentiation, T-Lymphocyte / Q000096:biosynthesis / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology; D017252:CD3 Complex / Q000276:immunology; D015704:CD4 Antigens / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D000073883:CX3C Chemokine Receptor 1; D003601:Cytotoxicity Tests, Immunologic; D005260:Female; D005434:Flow Cytometry; D005500:Follow-Up Studies; D005919:Glomerular Filtration Rate / Q000502:physiology*; D006801:Humans; D007111:Immunity, Cellular / Q000276:immunology*; D007694:Killer Cells, Natural / Q000276:immunology*; D037181:Lectins, C-Type; D008213:Lymphocyte Activation; D018655:Lymphocyte Count; D052118:Lysosomal-Associated Membrane Protein 1 / Q000096:biosynthesis / Q000276:immunology; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D051920:NK Cell Lectin-Like Receptor Subfamily D / Q000096:biosynthesis / Q000276:immunology; D055629:Natural Cytotoxicity Triggering Receptor 2; D010641:Phenotype; D011379:Prognosis; D019718:Receptors, CXCR4 / Q000096:biosynthesis / Q000276:immunology; D019707:Receptors, Chemokine / Q000096:biosynthesis / Q000276:immunology; D011971:Receptors, Immunologic / Q000096:biosynthesis / Q000276:immunology; D006435:Renal Dialysis / Q000379:methods*; D014511:Uremia / Q000276:immunology* / Q000503:physiopathology / Q000628:therapy; D000099192:CD69 Antigens
D015703:Antigens, CD; D018941:Antigens, CD19; D000945:Antigens, Differentiation, T-Lymphocyte; D017252:CD3 Complex; D015704:CD4 Antigens; D000073883:CX3C Chemokine Receptor 1; D037181:Lectins, C-Type; D052118:Lysosomal-Associated Membrane Protein 1; D051920:NK Cell Lectin-Like Receptor Subfamily D; D055629:Natural Cytotoxicity Triggering Receptor 2; D019718:Receptors, CXCR4; D019707:Receptors, Chemokine; D011971:Receptors, Immunologic; D000099192:CD69 Antigens; C095235:CX3CR1 protein, human; C527276:CXCR4 protein, human; C112837:NCR2 protein, human