title: Influence of FcγRIIIA genetic polymorphism on T-lymphocyte depletion induced by rabbit antithymocyte globulins in kidney transplant patients.
abstract: BACKGROUND
  Polyclonal antithymocyte globulins (ATG) have been used in transplantation for several decades, but the sources of the interindividual variability of their effect are poorly understood. An influence of the FCGR3A-158V/F genetic polymorphism on the horse ATG concentration-effect relationship was reported in kidney transplant patients. The objective of the present study was to confirm the influence of the FCGR3A polymorphism on the extent of lymphocyte depletion in kidney transplant patients treated with rabbit antithymocyte globulin (r-ATG).
  
  
  METHODS
  Of the 194 transplant patients treated with r-ATG between 1998 and 2002 in our institution, 69 patients were eligible and included in this retrospective study. Biomarkers of response were CD3 and CD4 counts. Dose-effect data were analyzed using a population approach, and a two-compartment turnover model with stimulation of lymphocyte 'output'. Since r-ATG concentrations were not available, a K-PD model was used. The influence of FCGR3A genotype on estimated parameters was investigated.
  
  
  RESULTS
  The r-ATG infusion rate leading to a 50% stimulation of CD3+ output (EDK(50)), which is inversely related to patient sensitivity to r-ATG treatment, decreased with the number of V alleles (P=0.0016).
  
  
  CONCLUSIONS
  The genetic polymorphism of FCGR3A influences r-ATG effect on CD3 count in kidney transplant patients, those with the V allele being more sensitive to antilymphocyte serum. These results also suggest that r-ATG act, at least in part, by antibody-dependent cellular cytotoxicity.
authors: aFrançois Rabelais University of Tours bCNRS, UMR 7292 'GICC' University of Tours cLaboratory of Pharmacology-Toxicology, University Hospital of Tours dLaboratory of Immunology eDepartment of Nephrology and Clinical Immunology, Tours, France.
authors: David
authors: D
authors: Ternant
authors: Matthias
authors: M
authors: Büchler
authors: Gilles
authors: G
authors: Thibault
authors: Marc
authors: M
authors: Ohresser
authors: Hervé
authors: H
authors: Watier
authors: Yvon
authors: Y
authors: Lebranchu
authors: Gilles
authors: G
authors: Paintaud
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D000961:Antilymphocyte Serum / Q000008:administration & dosage / Q000494:pharmacology*; D015415:Biomarkers; D017252:CD3 Complex / Q000032:analysis; D004305:Dose-Response Relationship, Drug; D005260:Female; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000494:pharmacology*; D007668:Kidney / Q000276:immunology; D016030:Kidney Transplantation; D018655:Lymphocyte Count; D008212:Lymphocyte Depletion; D008297:Male; D008875:Middle Aged; D008957:Models, Genetic; D020641:Polymorphism, Single Nucleotide; D011817:Rabbits; D017452:Receptors, IgG / Q000235:genetics*; D012189:Retrospective Studies; D013601:T-Lymphocytes / Q000276:immunology*; D014633:Valine / Q000235:genetics; D055815:Young Adult
chemical_list: D000961:Antilymphocyte Serum; D015415:Biomarkers; D017252:CD3 Complex; C496124:FCGR3A protein, human; D007166:Immunosuppressive Agents; D017452:Receptors, IgG; D014633:Valine