title: ABO antibody and complement depletion by immunoadsorption combined with membrane filtration--a randomized, controlled, cross-over trial.
abstract: BACKGROUND
  Potent antibody depletion techniques have paved the way to successful ABO-incompatible transplantation. Considering its efficiency regarding IgG removal, the use of non-antigen-specific semi-selective immunoadsorption (IA) has been advocated. One attractive strategy to overcome the caveat of incomplete IgM depletion and to interfere with complement activation could be the adjunctive use of membrane filtration (MF) to enhance the removal of macromolecules.
  
  
  METHODS
  To investigate the depletion efficiency of semi-selective IA plus MF, we conducted a randomized, controlled, cross-over trial including patients on regular IA treatment for indications outside recipient desensitization. According to the results of sample size calculation, 14 subjects were enrolled. Two treatment sequences, a single session of IA plus MF followed by IA alone after ≥7 days (and vice versa), were analysed.
  
  
  RESULTS
  IA plus MF markedly enhanced the median per cent reduction of ABO-specific IgM determined by flow cytometry (primary end point; 59 versus 23%, P < 0.001) and haemagglutination (2 versus 1 titre steps, P < 0.001), respectively. Combined treatment also substantially lowered C1q concentrations (86 versus 58% reduction, P < 0.001) and the functionality of classical complement as reflected by impaired in vitro C3 activation capability. IgG was strongly reduced without any additional effect of MF.
  
  
  CONCLUSIONS
  We demonstrate that the innovative strategy of combining MF with semi-selective IA may substantially increase IgM elimination and affect classical complement activation. Our findings suggest that this new treatment concept could be an efficient strategy for recipient desensitization in ABO- and HLA-incompatible transplantation.
authors.affiliation: Division of Nephrology and Dialysis, Department of Medicine III, Medical University of Vienna, Vienna, Austria.
authors.forename: Farsad
authors.initials: F
authors.lastname: Eskandary
authors.forename: Markus
authors.initials: M
authors.lastname: Wahrmann
authors.forename: Peter
authors.initials: P
authors.lastname: Biesenbach
authors.forename: Camilla
authors.initials: C
authors.lastname: Sandurkov
authors.forename: Franz
authors.initials: F
authors.lastname: König
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Schwaiger
authors.forename: Thomas
authors.initials: T
authors.lastname: Perkmann
authors.forename: Sarojinidevi
authors.initials: S
authors.lastname: Künig
authors.forename: Kurt
authors.initials: K
authors.lastname: Derfler
authors.forename: Gerhard J
authors.initials: GJ
authors.lastname: Zlabinger
authors.forename: Georg A
authors.initials: GA
authors.lastname: Böhmig
mesh_terms: D000017:ABO Blood-Group System / Q000276:immunology; D000327:Adsorption; D000328:Adult; D001323:Autoantibodies / Q000097:blood / Q000302:isolation & purification; D001787:Blood Group Incompatibility / Q000517:prevention & control; D015922:Complement C1q / Q000302:isolation & purification / Q000378:metabolism; D018592:Cross-Over Studies; D005260:Female; D006084:Graft Rejection / Q000517:prevention & control*; D006801:Humans; D007674:Kidney Diseases / Q000601:surgery; D016030:Kidney Transplantation; D008297:Male; D008567:Membranes, Artificial; D008875:Middle Aged; D006435:Renal Dialysis
chemical_list: D000017:ABO Blood-Group System; D001323:Autoantibodies; D008567:Membranes, Artificial; D015922:Complement C1q
keywords: ABO incompatibility; complement; immunoadsorption; immunoglobulins; randomized trial; transplantation