title: Limitations of rituximab/IVIg desensitization protocol in kidney transplantation; is this better than a tincture of time?
abstract: BACKGROUND
  A plasmapheresis-free protocol for desensitization of donor kidney transplant candidates with high Calculated Panel Reactive Antibody (CPRA) was initiated at our center. The protocol was adopted from previously published work by Vo, Jordan et al.
  
  
  METHODS
  Five patients with CPRA of 94 ± 18%, awaiting kidney transplant from living or deceased donors received rituximab (1 g × 2 doses) and intravenous immunoglobulin (IVIG 2 g/kg × 2 doses) without plasmapheresis. Levels of donor specific antibodies (DSA) and T/B cell crossmatches were followed using solid phase flow cytometry.
  
  
  RESULTS
  Three out of 5 patients were sensitized only to Class II HLA antigens. All patients had very high levels of alloantibodies before initiation of the treatment. All of the candidates initially demonstrated reduced levels of HLA antibody, but statistical significance was only obtained in one patient Class II antibody and in another only for Class I. Depletion was transient with observed antibody rebound. Rituximab effectively depleted CD20 cells in peripheral blood. None of the patients were transplanted due to persistently high levels of antibody and strong positive flow cytometry crossmatches. Under this protocol, reduction of HLA antibodies in patients with high levels was insufficient.
  
  
  CONCLUSIONS
  Highly allo-sensitized patients with a CPRA above 85% may not benefit from a combination of rituximab-IVIG alone. The previously published protocol does not help all patients achieve an acceptable crossmatch. An individualized approach to the treatment of highly sensitized patients is still required.
authors.affiliation: Department of Surgery, University of North Carolina at Chapel Hill, 27599, USA. tomasz_kozlowski@med.unc.edu
authors.forename: Tomasz
authors.initials: T
authors.lastname: Kozlowski
authors.forename: Kenneth
authors.initials: K
authors.lastname: Andreoni
mesh_terms: D000328:Adult; D058846:Antibodies, Monoclonal, Murine-Derived / Q000276:immunology / Q000627:therapeutic use*; D018951:Antigens, CD20 / Q000276:immunology; D002985:Clinical Protocols; D003888:Desensitization, Immunologic / Q000379:methods*; D005260:Female; D006084:Graft Rejection / Q000276:immunology; D006680:HLA Antigens / Q000276:immunology; D006650:Histocompatibility Testing / Q000379:methods; D006801:Humans; D016756:Immunoglobulins, Intravenous / Q000276:immunology / Q000627:therapeutic use*; D007155:Immunologic Factors / Q000276:immunology / Q000627:therapeutic use*; D007518:Isoantibodies / Q000276:immunology; D016030:Kidney Transplantation / Q000276:immunology / Q000379:methods*; D008297:Male; D008875:Middle Aged; D000069283:Rituximab
chemical_list: D058846:Antibodies, Monoclonal, Murine-Derived; D018951:Antigens, CD20; D006680:HLA Antigens; D016756:Immunoglobulins, Intravenous; D007155:Immunologic Factors; D007518:Isoantibodies; D000069283:Rituximab