title: Apoptosis of peripheral CD4(+) T-lymphocytes in end-stage renal disease patients under hemodialysis and rhEPO therapies.
abstract: End-stage renal disease (ESRD) under hemodialyses (HD) is related with a higher propensity to infections, essentially due to T-cell lymphopenia. We postulated that HD procedure affects CD4(+) T cells, especially by inducing apoptotic death and that recombinant human erythropoietin (rhEPO) therapy may also play an important role in the modulation of the immune system in these patients. T-cell phenotype and apoptosis of HD patients and healthy controls were evaluated by flow cytometry using anticoagulated whole-blood samples. In 12 HD patients, these parameters were also analyzed before and immediately after HD procedure. HD patients showed a decrease in total circulating CD3(+) lymphocytes, especially in CD4(+) T cells (0.747 ± 0.410 vs. 0.941 ± 0.216 × 10(9)/L, p < 0.05), which could be a consequence of the higher proportion of CD3(+) and CD4(+) lymphocytes in the latest stage of apoptosis (or death) and of the higher proportion of apoptotic CD4(+) T cells observed in the patients immediately after HD procedure (2.91 ± 0.780 vs. 3.90 ± 1.96, p < 0.05). A positive and statistically significant correlation between CD3(+) and CD4(+) lymphocytes in latest stage of apoptosis (or death) with HD time was found (CD3(+): r = 0.592, p < 0.01; CD4(+): r = 0.501, p < 0.01). We also found a negative and significant correlation between weekly rhEPO doses and the number of CD4(+) T cells (r = -0.358, p < 0.05). In conclusion, HD procedure still contributes to the development of T-cell lymphopenia, at least in part, by apoptosis induction. It was also shown that rhEPO therapy is associated with the CD4(+) T-cell decline, possibly by immune modulation, eliminating atypical cells and helping to restore the CD4(+) T-cell subset.
authors.affiliation: Faculdade de Farmácia, Serviço de Bioquímica, Universidade do Porto, Porto, Portugal.
authors.forename: Ana
authors.initials: A
authors.lastname: Borges
authors.forename: Margarida
authors.initials: M
authors.lastname: Borges
authors.forename: João
authors.initials: J
authors.lastname: Fernandes
authors.forename: Henrique
authors.initials: H
authors.lastname: Nascimento
authors.forename: Maria
authors.initials: M
authors.lastname: Sameiro-Faria
authors.forename: Vasco
authors.initials: V
authors.lastname: Miranda
authors.forename: Flávio
authors.initials: F
authors.lastname: Reis
authors.forename: Luis
authors.initials: L
authors.lastname: Belo
authors.forename: Elisio
authors.initials: E
authors.lastname: Costa
authors.forename: Alice
authors.initials: A
authors.lastname: Santos-Silva
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D017304:Annexin A5 / Q000032:analysis; D017209:Apoptosis; D015415:Biomarkers / Q000032:analysis; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000502:physiology; D016022:Case-Control Studies; D003430:Cross-Sectional Studies; D004921:Erythropoietin / Q000009:adverse effects*; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007676:Kidney Failure, Chronic / Q000276:immunology* / Q000628:therapy; D008231:Lymphopenia / Q000209:etiology*; D008297:Male; D008875:Middle Aged; D011994:Recombinant Proteins; D006435:Renal Dialysis / Q000009:adverse effects*
chemical_list: D017304:Annexin A5; D015415:Biomarkers; D011994:Recombinant Proteins; D004921:Erythropoietin