title: CCR5Δ32 genotype leads to a Th2 type directed immune response in ESRD patients.
abstract: BACKGROUND
  In patients with end stage renal disease (ESRD) we observed protection from inflammation-associated mortality in CCR5Δ32 carriers, leading to CCR5 deficiency, suggesting impact of CCR5Δ32 on inflammatory processes. Animal studies have shown that CCR5 deficiency is associated with a more pronounced Th2 type immune response, suggesting that in human CCR5Δ32 carriers the immune response may be more Th2 type directed. So, in the present study we determined the Th1-Th2 type directed immune response in ESRD patients carrying and not carrying the CCR5Δ32 genetic variant after stimulation.
  
  
  RESULTS
  We tested this hypothesis by determining the levels of IFN-γ and IL-4 and the distribution of Th1, Th2 and Th17 directed circulating CD4+ and CD8+ T cells and regulatory T cells (Tregs) after stimulation in ESRD patients with (n = 10) and without (n = 9) the CCR5Δ32 genotype. The extracellular levels of IFN-γ and IL-4 did not differ between CCR5Δ32 carriers and non carriers. However, based on their intracellular cytokine profile the percentages IL-4 secreting CD4+ and CD8+ T cells carrying the CCR5Δ32 genotype were significantly increased (p = 0.02, respectively p = 0.02) compared to non carriers, indicating a more Th2 type directed response. Based on their intracellular cytokine profile the percentages IFN-γ and IL-17 secreting T cells did not differ between carriers and non-carriers nor did the percentage Tregs, indicating that the Th1, Th17 and T regulatory response was not affected by the CCR5Δ32 genotype.
  
  
  CONCLUSIONS
  This first, functional human study shows a more pronounced Th2 type immune response in CCR5Δ32 carriers compared to non carriers. These differences may be involved in the previously observed protection from inflammation-associated mortality in ESRD patients carrying CCR5Δ32.
authors.affiliation: Internal Medicine, Vasculair Medicine, University Medical Center Groningen, Groningen, The Netherlands. f.l.h.muntinghe@umcg.nl
authors.forename: Friso L H
authors.initials: FL
authors.lastname: Muntinghe
authors.forename: Wayel H
authors.initials: WH
authors.lastname: Abdulahad
authors.forename: Minke G
authors.initials: MG
authors.lastname: Huitema
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Damman
authors.forename: Marc A
authors.initials: MA
authors.lastname: Seelen
authors.forename: Simon P M
authors.initials: SP
authors.lastname: Lems
authors.forename: Bouke G
authors.initials: BG
authors.lastname: Hepkema
authors.forename: Gerjan
authors.initials: G
authors.lastname: Navis
authors.forename: Johanna
authors.initials: J
authors.lastname: Westra
mesh_terms: D000328:Adult; D000368:Aged; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D016207:Cytokines; D005260:Female; D014644:Genetic Variation / Q000276:immunology*; D005838:Genotype; D006801:Humans; D007249:Inflammation / Q000235:genetics; D015847:Interleukin-4 / Q000097:blood; D007676:Kidney Failure, Chronic / Q000235:genetics / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D019713:Receptors, CCR5 / Q000172:deficiency / Q000235:genetics*; D018418:Th2 Cells / Q000276:immunology*
chemical_list: D016207:Cytokines; D019713:Receptors, CCR5; D015847:Interleukin-4