title: Plasmapheresis and intravenous immune globulin provides effective rescue therapy for refractory humoral rejection and allows kidneys to be successfully transplanted into cross-match-positive recipients.
abstract: BACKGROUND
  Hyperacute rejection (HAR) and acute humoral rejection (AHR) remain recalcitrant conditions without effective treatments, and usually result in graft loss. Plasmapheresis (PP) has been shown to remove HLA- specific antibody (Ab) in many different clinical settings. Intravenous gamma globulin (IVIG) has been used to suppress alloantibody and modulate immune responses. Our hypothesis was that a combination of PP and IVIG could effectively and durably remove donor-specific, anti-HLA antibody (Ab), rescuing patients with established AHR and preemptively desensitizing recipients who had positive crossmatches with a potential live donor.
  
  
  METHODS
  The study patients consisted of seven live donor kidney transplant recipients who experienced AHR and had donor-specific Ab (DSA) for one or more mismatched donor HLA antigens. The patients segregated into two groups: three patients were treated for established AHR (rescue group) and four cross-match-positive patients received therapy before transplantation (preemptive group).
  
  
  RESULTS
  Using PP/IVIG we have successfully reversed established AHR in three patients. Four patients who were cross-match-positive (3 by flow cytometry and 1 by cytotoxic assay) and had DSA before treatment underwent successful renal transplantation utilizing their live donor. The overall mean creatinine for both treatment groups is 1.4+/-0.8 with a mean follow up of 58+/-40 weeks (range 17-116 weeks).
  
  
  CONCLUSIONS
  In this study, we present seven patients for whom the combined therapies of PP/IVIG were successful in reversing AHR mediated by Ab specific for donor HLA antigens. Furthermore, this protocol shows promise for eliminating DSA preemptively among patients with low-titer positive antihuman globulin-enhanced, complement-dependent cytotoxicity (AHG-CDC) cross-matches, allowing the successful transplantation of these patients using a live donor without any cases of HAR.
authors.affiliation: Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
authors.forename: R A
authors.initials: RA
authors.lastname: Montgomery
authors.forename: A A
authors.initials: AA
authors.lastname: Zachary
authors.forename: L C
authors.initials: LC
authors.lastname: Racusen
authors.forename: M S
authors.initials: MS
authors.lastname: Leffell
authors.forename: K E
authors.initials: KE
authors.lastname: King
authors.forename: J
authors.initials: J
authors.lastname: Burdick
authors.forename: W R
authors.initials: WR
authors.lastname: Maley
authors.forename: L E
authors.initials: LE
authors.lastname: Ratner
mesh_terms: D000328:Adult; D000368:Aged; D000906:Antibodies / Q000097:blood; D000917:Antibody Formation / Q000502:physiology; D000918:Antibody Specificity; D005260:Female; D006084:Graft Rejection / Q000276:immunology* / Q000473:pathology / Q000628:therapy*; D006650:Histocompatibility Testing; D006801:Humans; D016756:Immunoglobulins, Intravenous; D007668:Kidney / Q000473:pathology; D016030:Kidney Transplantation / Q000276:immunology* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D010956:Plasmapheresis; D012307:Risk Factors
chemical_list: D000906:Antibodies; D016756:Immunoglobulins, Intravenous