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

Abstract

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%.

Therapeutic preparations of IVIg contain naturally occurring anti–HLA-E antibodies that react with HLA-Ia (HLA-A/-B/-Cw) alleles

“…In the second study, 7 titled "infusion of high-dose intravenous immunoglobulin fails to lower the strength of human leukocyte antigen antibodies in highly sensitized patients," the authors confirmed that HLA antibody profiles, measured by calculated PRA, showed no significant change in response to IVIg treatment. The third study 8 also documented that IVIg-even with rituximab-did not lead to any significant reduction in patients' anti-HLA-Ia Abs calculated by PRA levels or MFI measured with Luminex single antigen beads. Importantly, none of these studies corroborate previous claims of the reduction of HLA antibodies (calculated panel reactive antibody) in sensitized patients undergoing desensitization with high-dose IVIg.…”

“…Three recent clinical studies document that IVIg preparations were unable to reduce HLA Abs. [6][7][8] In the first, 6 IVIg failed to lower the mean percentage of pretransplant HLA Abs observed before IVIg infusion (85% before, 80% after IVIg; P 5 .1). On the contrary, an increase in anti-HLA-Ia Abs was observed after IVIg in 27% of the patients.…”

“…Since that time, IVIg has emerged as a potential treatment strategy for desensitization protocols and also for lowering the incidence of donor-specific Abs (DSA) involved in Ab-mediated rejection (AMR). Several transplant centers [2][3][4][5][6][7][8] have adopted the protocol of IVIg administration for patients awaiting transplantation and for allograft recipients in order to reduce allo-HLA Abs or DSA directed against the HLA of donor kidneys.…”

The Clinical and Genomic Significance of Donor-Specific Antibody–Positive/C4d-Negative and Donor-Specific Antibody–Negative/C4d-Negative Transplant Glomerulopathy

“…The methods for microarray analysis are described in detail in our previous publications (20,21). Gene Set libraries were taken from the Molecular Signatures Database (22), and new libraries were generated by mapping HUGO gene identifiers to the University of Alberta, Edmonton, pathogenesis-based transcripts (PBT; http:// transplants.med.ualberta.ca/Nephlab/data/gene_lists.…”

Transplanting Against Histocompatibility Barriers

“…Recently Marfu et al examined the use of IVIG (2g/kg) and rituximab (1 dose 375mg/m2) for immunomodulation of patients on the deceased donor waiting list [80]. They found that in patients with cPRA >50%, treatment with IVIG and rituximab did not increase rates of transplantation.…”