Frequency of HLA-DP-specific antibodies and a possible new cross-reacting group

Callender, Carly J.; Fernández-Viña, Marcelo; Leffell, Mary S.

doi:10.1016/j.humimm.2011.11.006

Cited by 16 publications

(14 citation statements)

References 11 publications

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“…Recent evidence showed that even low levels of pre-transplant C’-binding DSA were associated with early AMR, although DSA against HLA-DP were not studied [15]. Others found that sensitization to DP is caused by transplants and blood transfusions as well as cross-reactivities with other antigens (for example, DR antigens [16]) by sharing common eplets [13,17,18]. Another mechanism of sensitization, epitope (eplet) spreading, is an expansion of the immune response from an inducing epitope (eplet) to non-cross-reactive epitopes (eplets) [19,20] and has been shown to have a boosting effect, especially with recurring rejections [21].…”

Section: Discussionmentioning

confidence: 99%

Early acute antibody-mediated rejection of a negative flow crossmatch 3rd kidney transplant with exclusive disparity at HLA-DP

Mierzejewska¹,

Schroder²,

Baum³

et al. 2014

Human Immunology

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Donor-specific alloantibodies (DSA) to HLA-DP may cause antibody-mediated rejection (AMR), especially in re-transplants. We describe the immunization history of a patient who received 3 kidney transplants; the 3rd kidney was completely matched except at DPA1 and DPB1. Prior to the 3rd transplant, single antigen bead analysis (SAB) showed DSA reactivity against DPA1 shared by the 1st and 3rd donors, but B and T flow crossmatch (FXM) results were negative. Within 11 days the 3rd transplant underwent acute C4d+ AMR which coincided with the presence of complement (C1q)-binding IgG1 DSA against donor DPA1 and DPB1. Using HLAMatchmaker and SAB, we provide evidence that eplet (epitope) spreading on DPA1 and eplet sharing on differing DPB1 alleles of the 1st and 3rd transplants was associated with AMR. Since weak DSA to DPA1/DPB1 may induce acute AMR with negative FXM, donor DPA1/DPB1 high resolution typing should be considered in sensitized patients with DP-directed DSA.

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Section: Discussionmentioning

confidence: 99%

Early acute antibody-mediated rejection of a negative flow crossmatch 3rd kidney transplant with exclusive disparity at HLA-DP

Mierzejewska¹,

Schroder²,

Baum³

et al. 2014

Human Immunology

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“…Two sequence dimorphisms of DPB1 define the immunodominant serologic epitopes of HLA-DP. Callender et al (94) showed that while 42% of 650 patients on a renal waiting list had DP antibody, nearly 80% had antibody to the cross-reactive DR antigens. The strengths of most of the antibodies was low with only 3 of the 271 sera yielding a positive cytotoxicity crossmatch.…”

Section: Hla-matching Strategies For Sensitized Patientsmentioning

confidence: 99%

HLA Mismatching Strategies for Solid Organ Transplantation – A Balancing Act

Zachary

Leffell

2016

Front. Immunol.

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HLA matching provides numerous benefits in organ transplantation including better graft function, fewer rejection episodes, longer graft survival, and the possibility of reduced immunosuppression. Mismatches are attended by more frequent rejection episodes that require increased immunosuppression that, in turn, can increase the risk of infection and malignancy. HLA mismatches also incur the risk of sensitization, which can reduce the opportunity and increase waiting time for a subsequent transplant. However, other factors such as donor age, donor type, and immunosuppression protocol, can affect the benefit derived from matching. Furthermore, finding a well-matched donor may not be possible for all patients and usually prolongs waiting time. Strategies to optimize transplantation for patients without a well-matched donor should take into account the immunologic barrier represented by different mismatches: what are the least immunogenic mismatches considering the patient’s HLA phenotype; should repeated mismatches be avoided; is the patient sensitized to HLA and, if so, what are the strengths of the patient’s antibodies? This information can then be used to define the HLA type of an immunologically optimal donor and the probability of such a donor occurring. A probability that is considered to be too low may require expanding the donor population through paired donation or modifying what is acceptable, which may require employing treatment to overcome immunologic barriers such as increased immunosuppression or desensitization. Thus, transplantation must strike a balance between the risk associated with waiting for the optimal donor and the risk associated with a less than optimal donor.

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“…Reactivity to DP is less common than to DR or DQ. Anti‐DP antibodies are detectable in 5–40% of wait‐listed patients, and up to 60% or more in those with failed transplants . Sensitized waiting list patients less commonly reacted to DP antigens (35%) than DR (66%) and DQ (69%).…”

Section: Antibodies Against Cw and Dpmentioning

confidence: 99%

“…Early studies suggested that HLA‐DP mismatch did not adversely affect GS , except possibly in retransplants or in highly sensitized patients . As most patients with DP antibodies also have anti‐DR and or DQ antibodies, the role of DP specifically has been hard to assess . High‐resolution typing and epitope analysis by HLA Matchmaker have allowed identification of patients with isolated anti‐DP antibodies that have suffered AMR and GL .…”

Section: Antibodies Against Cw and Dpmentioning

confidence: 99%

Humoral immunity in renal transplantation: epitopes, Cw and DP, and complement‐activating capability – an update

Filippone

Farber

2015

Clinical Transplantation

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Humoral immune responses can destroy a renal allograft. In January 2013, Consensus Guidelines were published regarding testing and management concerns with respect to antibodies in transplantation. New studies have been reported over the past two yr and controversies remain. We review here the new data in light of the Consensus Guidelines and the relevant prior research with emphasis on antibody characteristics and potential for pathogenicity. The heart of immune recognition, epitopes, is stressed, including the realization that DQ (and probably DP) epitopes may be determined not only by eplets within a given α- or β-chain, but also by specific α- and β-chain pairings. The significance of Cw and DP loci are discussed. To better understand which donor-specific antibodies are pathogenic, IgG subclass determination has been studied, and in in vitro complement fixation assays, such as the C4d and C1q assays, have been evaluated.

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Frequency of HLA-DP-specific antibodies and a possible new cross-reacting group

Cited by 16 publications

References 11 publications

Early acute antibody-mediated rejection of a negative flow crossmatch 3rd kidney transplant with exclusive disparity at HLA-DP

Early acute antibody-mediated rejection of a negative flow crossmatch 3rd kidney transplant with exclusive disparity at HLA-DP

HLA Mismatching Strategies for Solid Organ Transplantation – A Balancing Act

Humoral immunity in renal transplantation: epitopes, Cw and DP, and complement‐activating capability – an update

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