Lack of effect in desensitization with intravenous immunoglobulin and rituximab in highly sensitized patients

Transplantation. 2012 Aug 27;94(4):345-51. doi: 10.1097/TP.0b013e3182590d2e.

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.

Conclusion: 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%.

MeSH terms

  • Adult
  • Antibodies, Monoclonal, Murine-Derived / administration & dosage*
  • Cohort Studies
  • Female
  • Gene Expression Profiling
  • HLA Antigens / immunology
  • Humans
  • Hypersensitivity / drug therapy*
  • Immunoglobulins, Intravenous / administration & dosage*
  • Isoantibodies / blood
  • Kidney Transplantation
  • Male
  • Middle Aged
  • Prospective Studies
  • Rituximab
  • Tissue Donors

Substances

  • Antibodies, Monoclonal, Murine-Derived
  • HLA Antigens
  • Immunoglobulins, Intravenous
  • Isoantibodies
  • Rituximab