title: Antibody-dependent cellular cytotoxicity in patients on chronic hemodialysis.
abstract: BACKGROUND
  Antibody (Ab)-dependent cellular cytotoxicity (ADCC) is considered to be a relevant mechanism of action of Ab-based tumor therapies. However, knowledge about ADCC capacity of dialysis patients (DP) is limited. The aim of our study was to investigate if ADCC capacity of effector cells obtained from DP differed from those of healthy individuals (HI).
  
  
  METHODS
  First, we performed ADCC assays with isolated polymorphonuclear cells (PMN) and peripheral blood mononuclear cells (PBMC), mediated by the epidermal growth factor receptor Ab cetuximab or panitumumab. As cetuximab is of human IgG1 and panitumumab of human IgG2 isotype, both Abs differ in their affinity to Fcγ receptors and effector cell recruitment.
  
  
  RESULTS
  Using PMN as effectors, ADCC levels via panitumumab proved to be higher than via cetuximab, but did not differ between DP and HI. In contrast, IgG2-mediated ADCC with PBMC from DP was significantly enhanced compared to HI. IgG2 Abs predominantly bind to FcγRIIa. Within the PBMC, monocytes are the only cytotoxic cells physiologically expressing this receptor. ADCC experiments with isolated monocytes confirmed them to be the pivotal cells for the observed effect. Analysis of monocytes' Fc receptor expression demonstrated no difference between DP and HI, but monocytes of DP proved to be numerically increased and appeared preactivated.
  
  
  CONCLUSIONS
  Our studies implicate that ADCC capacity is not impaired in DP and that it might particularly be reasonable to apply human IgG2 Abs as therapeutics for these patients.
authors.affiliation: Department of Internal Medicine IV, Nephrology and Hypertension, Christian Albrechts University, Kiel, Germany.
authors.forename: Till
authors.initials: T
authors.lastname: Koch
authors.forename: Stefanie
authors.initials: S
authors.lastname: Derer
authors.forename: Matthias
authors.initials: M
authors.lastname: Staudinger
authors.forename: Kai
authors.initials: K
authors.lastname: Rossen
authors.forename: Pia
authors.initials: P
authors.lastname: Glorius
authors.forename: Matthias
authors.initials: M
authors.lastname: Peipp
authors.forename: Christian
authors.initials: C
authors.lastname: Kellner
authors.forename: Ulrich
authors.initials: U
authors.lastname: Kunzendorf
authors.forename: Thomas
authors.initials: T
authors.lastname: Valerius
authors.forename: Michael
authors.initials: M
authors.lastname: Dechant
mesh_terms: D000906:Antibodies / Q000627:therapeutic use*; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D061067:Antibodies, Monoclonal, Humanized / Q000494:pharmacology; D000920:Antibody-Dependent Cell Cytotoxicity / Q000276:immunology*; D045744:Cell Line, Tumor; D000068818:Cetuximab; D006801:Humans; D007074:Immunoglobulin G / Q000737:chemistry; D015850:Interleukin-6 / Q000378:metabolism; D016209:Interleukin-8 / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000276:immunology; D009000:Monocytes / Q000166:cytology; D009504:Neutrophils / Q000276:immunology; D000077544:Panitumumab; D011961:Receptors, Fc / Q000737:chemistry; D006435:Renal Dialysis / Q000379:methods*; D051437:Renal Insufficiency / Q000097:blood / Q000276:immunology
chemical_list: D000906:Antibodies; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D007074:Immunoglobulin G; D015850:Interleukin-6; D016209:Interleukin-8; D011961:Receptors, Fc; D000077544:Panitumumab; D000068818:Cetuximab