Lack of Effect in Desensitization With Intravenous Immunoglobulin and Rituximab in Highly Sensitized Patients.

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). 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% (read more)