title: Lack of effect in desensitization with intravenous immunoglobulin and rituximab in highly sensitized patients.
abstract: BACKGROUND
  We conducted a prospective cohort study in highly sensitized kidney transplant candidates with a calculated panel reactive antibody (cPRA) greater than 50% and on the deceased-donor waiting list for more than 5 years to investigate the effects of intravenous immunoglobulin (IVIG) and rituximab treatment.
  
  
  METHODS
  Desensitization protocol included two doses of IVIG (2 g/kg, max 120 g each dose) and a single dose of rituximab (375 mg/m(2)). Patients were followed up monthly by Luminex single antigen beads. Whole blood gene expression profiles were studied by Affymetrix Human 1.0 ST GeneChips before and after treatment.
  
  
  RESULTS
  Forty patients were eligible for desensitization treatment. Thirteen of these patients agreed to participate, and 11 completed the treatment. After a mean follow-up of 334 ± 82 days, two desensitized patients (18%) received a kidney transplant compared with 14 patients (52%) in the nondesensitized group. Comparing with 14 patients who received transplants without any desensitization treatment, desensitized patients showed higher class I (99% vs. 80%) and class II (98% vs. 69%) cPRA levels and more unacceptable antigens (32 vs. 8). Desensitization treatment did not lead to any significant reduction in patients' class I and II cPRA levels and any change in the mean number of unacceptable antigens or their mean fluorescence intensity values. Whole blood gene expression analysis by microarrays demonstrated down-regulation of immunoglobulin and B-cell-associated transcripts after treatment.
  
  
  CONCLUSIONS
  These results suggested that pretransplant desensitization with IVIG and rituximab was not successful in highly sensitized kidney transplant candidates with cPRA levels higher than 90%.
authors: Montefiore Einstein Center for Transplantation, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, NY 10467, USA.
authors: Kwaku
authors: K
authors: Marfo
authors: Ming
authors: M
authors: Ling
authors: Yi
authors: Y
authors: Bao
authors: Brant
authors: B
authors: Calder
authors: Bin
authors: B
authors: Ye
authors: Nicole
authors: N
authors: Hayde
authors: Stuart
authors: S
authors: Greenstein
authors: Javier
authors: J
authors: Chapochnick-Friedman
authors: Daniel
authors: D
authors: Glicklich
authors: Graciela
authors: G
authors: de Boccardo
authors: Milan
authors: M
authors: Kinkhabwala
authors: Enver
authors: E
authors: Akalin
mesh_terms: D000328:Adult; D058846:Antibodies, Monoclonal, Murine-Derived / Q000008:administration & dosage*; D015331:Cohort Studies; D005260:Female; D020869:Gene Expression Profiling; D006680:HLA Antigens / Q000276:immunology; D006801:Humans; D006967:Hypersensitivity / Q000188:drug therapy*; D016756:Immunoglobulins, Intravenous / Q000008:administration & dosage*; D007518:Isoantibodies / Q000097:blood; D016030:Kidney Transplantation; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D000069283:Rituximab; D014019:Tissue Donors
chemical_list: D058846:Antibodies, Monoclonal, Murine-Derived; D006680:HLA Antigens; D016756:Immunoglobulins, Intravenous; D007518:Isoantibodies; D000069283:Rituximab