Poor response to recombinant erythropoietin is associated with loss of T-lymphocyte CD28 expression and altered interleukin-10 production.
BACKGROUND
Recombinant erythropoietin (Epo) therapy is well established as an effective treatment for the anaemia of end-stage renal disease. However, 5-10% of such patients do not respond adequately and an important contributory factor to this is chronic inflammation.


METHODS
The present study compares the circulating T-cell phenotypes of haemodialysis patients who respond poorly to Epo with those who respond well, along with normal controls. Isolated peripheral blood mononuclear cells were labelled with immunofluorescent monoclonal antibodies to surface antigens and analysed by flow cytometry. In vitro mononuclear cell cytokine secretion was also studied in the three subject groups. The cells were cultured for 48 h either without stimulus, with lipopolysaccharide or with monoclonal antibodies to CD3 and CD28.


RESULTS
C-reactive protein levels were increased in poor responders to Epo (18.6 +/- 20.7 mg/l) compared with good responders (8.7 +/- 8.0 mg/l) and normal controls (3.8 +/- 1.1 mg/l). Patients responding poorly to Epo had increased circulating levels of CD4+/CD28- and CD8+/CD28- T-cells compared with patients responding well to Epo and normal controls. Unstimulated mononuclear cells from poor responders showed increased in vitro generation of interleukin-10 (IL-10) compared with both patients responding well to Epo and normal controls. Additionally, IL-10 generation stimulated by monoclonal antibodies to CD3 and CD28 was increased in poor responders compared with normal controls.


CONCLUSIONS
These findings suggest that patients responding poorly to Epo may show enhanced immune activation as manifest by changes in both T-cell function and phenotype.
Cooper
Angela C
AC
Department of Immunology, Guy's, King's and St Thomas' School of Medicine, King's College Hospital, London, UK. angela.redrup@kcl.ac.uk
Breen
Cormac P
CP
Vyas
Beejal
B
Ochola
Josephine
J
Kemeny
David M
DM
Macdougall
Iain C
IC
D000328:Adult; D000367:Age Factors; D000740:Anemia / Q000097:blood / Q000188:drug therapy*; D015703:Antigens, CD / Q000097:blood; D002097:C-Reactive Protein; D018106:CD28 Antigens / Q000097:blood*; D015704:CD4 Antigens / Q000097:blood; D004921:Erythropoietin / Q000009:adverse effects / Q000627:therapeutic use*; D005434:Flow Cytometry; D006454:Hemoglobins / Q000032:analysis; D006801:Humans; D016753:Interleukin-10 / Q000097:blood*; D007676:Kidney Failure, Chronic / Q000150:complications*; D007958:Leukocyte Count; D018655:Lymphocyte Count; D008875:Middle Aged; D011237:Predictive Value of Tests; D011994:Recombinant Proteins; D013601:T-Lymphocytes / Q000276:immunology*; D017211:Treatment Failure
D015703:Antigens, CD; D018106:CD28 Antigens; D015704:CD4 Antigens; D006454:Hemoglobins; D011994:Recombinant Proteins; D004921:Erythropoietin; D016753:Interleukin-10; D002097:C-Reactive Protein