title: Intravenous immunoglobulin reduces anti-HLA alloreactivity and shortens waiting time to cardiac transplantation in highly sensitized left ventricular assist device recipients.
abstract: BACKGROUND
  Recipients of left ventricular assist devices (LVADs) develop prominent B-cell hyperreactivity. We investigated the influence of anti-HLA antibodies on waiting time to cardiac transplantation in LVAD recipients and compared the effects of 2 immunomodulatory regimens on anti-HLA serum reactivity.
  
  
  RESULTS
  Fifty-five previously nonsensitized LVAD recipients of a TCI device implanted between 1990 and 1996 were studied. Patients with anti-HLA antibodies received monthly courses of either intravenous immunoglobulin (IVIg) or plasmapheresis, in conjunction with cyclophosphamide. The effects of these regimens on anti-HLA alloreactivity and waiting time to transplantation were then determined by Kaplan-Meier log-rank statistics, nonparametric Wilcoxon rank-sum test, and Student's t test. Prolongation in transplant waiting time was related to serum IgG anti-HLA class I alloreactivity. Infusion of IVIg (2 g/kg) caused a mean reduction of 33% in anti-HLA class I alloreactivity within 1 week. Waiting time to transplantation was significantly reduced by IVIg therapy and subsequently approximated that in nonsensitized patients. Side effects of IVIg (2 g/kg) were minimal and related primarily to immune complex disease. Although plasmapheresis caused a similar reduction in alloreactivity to IVIg, this effect was achieved after longer treatment. Moreover, plasmapheresis was associated with an unacceptably high frequency of infectious complications. In patients resistant to low-dose (2 g/kg) IVIg therapy, high-dose (3 g/kg) IVIg was effective in reducing alloreactivity but was associated with a high incidence of reversible renal insufficiency.
  
  
  CONCLUSIONS
  These results indicate that IVIg is an effective and safe modality for sensitized recipients awaiting cardiac transplantation, reducing serum anti-HLA alloreactivity and shortening the duration to transplantation. The therapeutic and safety profile of IVIg would appear to be superior to plasmapheresis.
authors.affiliation: College of Physicians and Surgeons of Columbia University, New York, NY 10032, USA.
authors.forename: R
authors.initials: R
authors.lastname: John
authors.forename: K
authors.initials: K
authors.lastname: Lietz
authors.forename: E
authors.initials: E
authors.lastname: Burke
authors.forename: J
authors.initials: J
authors.lastname: Ankersmit
authors.forename: D
authors.initials: D
authors.lastname: Mancini
authors.forename: N
authors.initials: N
authors.lastname: Suciu-Foca
authors.forename: N
authors.initials: N
authors.lastname: Edwards
authors.forename: E
authors.initials: E
authors.lastname: Rose
authors.forename: M
authors.initials: M
authors.lastname: Oz
authors.forename: S
authors.initials: S
authors.lastname: Itescu
mesh_terms: D006084:Graft Rejection / Q000517:prevention & control; D006331:Heart Diseases / Q000276:immunology / Q000503:physiopathology / Q000601:surgery*; D016027:Heart Transplantation; D006352:Heart Ventricles / Q000276:immunology* / Q000503:physiopathology*; D006353:Heart-Assist Devices; D006650:Histocompatibility Testing; D006801:Humans; D016756:Immunoglobulins, Intravenous / Q000008:administration & dosage*; D007518:Isoantibodies / Q000276:immunology; D013997:Time Factors; D014181:Transplantation Immunology; D014184:Transplantation, Homologous
chemical_list: D016756:Immunoglobulins, Intravenous; D007518:Isoantibodies