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Review
. 2014 Mar;258(1):183-207.
doi: 10.1111/imr.12150.

Desensitization for solid organ and hematopoietic stem cell transplantation

Andrea A Zachary  1 , Mary S Leffell
Affiliations
Review

Desensitization for solid organ and hematopoietic stem cell transplantation

Andrea A Zachary et al. Immunol Rev. 2014 Mar.

Abstract

Desensitization protocols are being used worldwide to enable kidney transplantation across immunologic barriers, i.e. antibody to donor HLA or ABO antigens, which were once thought to be absolute contraindications to transplantation. Desensitization protocols are also being applied to permit transplantation of HLA mismatched hematopoietic stem cells to patients with antibody to donor HLA, to enhance the opportunity for transplantation of non-renal organs, and to treat antibody-mediated rejection. Although desensitization for organ transplantation carries an increased risk of antibody-mediated rejection, ultimately these transplants extend and enhance the quality of life for solid organ recipients, and desensitization that permits transplantation of hematopoietic stem cells is life saving for patients with limited donor options. Complex patient factors and variability in treatment protocols have made it difficult to identify, precisely, the mechanisms underlying the downregulation of donor-specific antibodies. The mechanisms underlying desensitization may differ among the various protocols in use, although there are likely to be some common features. However, it is likely that desensitization achieves a sort of immune detente by first reducing the immunologic barrier and then by creating an environment in which an autoregulatory process restricts the immune response to the allograft.

Keywords: desensitization; donor-specific antibodies; hematopoietic stem cell transplantation; intravenous immunoglobulin; plasmapheresis; solid organ transplantation.

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Figures

Figure 1
Figure 1
Numbers of transplants decrease and waiting time increases with increasing breadth of sensitization. Percent panel reactive antibody (PRA) was used until 2009 as the measure of the breadth of sensitization and reflected the number of individuals in a panel, selected to represent a wide array of HLA antigens, with whom a patient's serum gave a positive crossmatch. Patients are divided into three PRA groups: low or no sensitization (0–19), moderately sensitized (20–79), and highly sensitized (≥80). Bars represent the numbers of transplants occurring during the first and second year on a waiting list for deceased donor transplantation, and the line represents the median waiting time.
Figure 2
Figure 2
Sensitization rates vary among patients categorized by either race or gender. In these graphs, the panel reactive antibody (PRA) categories differ from those in Fig. 1 with PRA 0–9 considered non-sensitized. (A) The highest frequency of sensitization (>30%) occurs in African-Americans with 10% of patients being very highly sensitized (PRA ≥80%). (B) The frequency of sensitization in females is twice that in males and the difference is even greater among the very highly sensitized.
Figure 3
Figure 3
The incidence of antibody-mediated rejection (AMR) among patients with donor-specific antibody (DSA) that persists after transplantation is affected by both strength and specificity of the antibody. The incidence of AMR among patients with low levels of antibody (ELISA−/Bead+) is only slightly higher than among patients with no persistent DSA. However, there is a substantially increased incidence of AMR among patients with DSA strong enough to be positive in an ELISA. The highest risk of AMR is for DSA to HLA class I antigens among patients with ELISA+ DSA and for DSA to HLA-DRB1 and/or -DQ for lower levels of antibody. Antibodies to antigens encoded by HLA-DRB3-5 carried the lowest risk of AMR at either level of antibody.
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References

    1. Organ Procurement and Transplantation Network (OPTN) and Scientific Registry of Transplant Recipients (SRTR) OPTN/SRTR 2011 Annual Data Report. Rockville, MD: Department of Health and Human Services, Health Resources and Services Administration, Healthcare Systems Bureau, Division of Transplantation; 2012. The data and analyses reported in the 2011 Annual Data Report of the Organ Procurement and Transplantation Network and the US Scientific Registry of Transplant Recipients have been supplied by the Minneapolis Medical Research Foundation and UNOS under contract with HHS/HRSA. The authors alone are responsible for reporting and interpreting these data; the views expressed herein are those of the authors and not necessarily those of the US Government.
    1. OPTN data as of September 20, 2013 for patients listed and transplanted between 2001-2002. 2013. Available from http://optn.transplant.hrsa.gov.
    1. Leffell MS, Steinberg AG, Bias WB, Machan CH, Zachary AA. The distribution of HLA antigens and phenotypes among donors and patients in the UNOS registry. Transplantation. 1994;58:1119–1130. - PubMed
    1. Zachary AA, Steinberg AG, Bias WB, Leffell MS. The frequencies of HLA alleles and haplotypes and their distribution among donors and renal patients in the UNOS registry. Transplantation. 1996;62:272–283. - PubMed
    1. Annual Report of the U.S. Organ Procurement and Transplantation Network and the Scientific Registry of Transplant Recipients: Transplant Data 1994-2003; Department of Health and Human Services Administration, Healthcare Systems Bureau, Division of Transplantation, Rockville, MD; United Network for Organ Sharing, Richmond, VA; University Renal Research and Education Association, Ann Arbor, MI. 2004.

MeSH terms