Structural aspects of human leukocyte antigen class I epitopes detected by human monoclonal antibodies

Duquesnoy, René J.; Marrari, Marilyn; Mulder, Arend; Claas, Frans H.J.; Mostecki, Justin; Balazs, Iván

doi:10.1016/j.humimm.2011.11.011

Cited by 40 publications

(37 citation statements)

References 46 publications

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“…26 Thus, an auto reactive component is also required for alloantibody responses to an HLA mismatch. 27 In the present study, in accordance with Lopes and associates, 7 we confirmed that a transplant has a high immunizing effect for both HLA class I and II compared with pregnancy and transfusion. Likewise, when we compared the antibody strengths (MFI values), as also reported by several authors, 6,28,29 we confirmed that a transplant, mainly for HLA class II, has a significantly higher antibody strength than pregnancy or transfusion.…”

Section: Discussionsupporting

confidence: 92%

Untitled

Resse¹,

Paolillo²,

Minucci³

et al. 2018

Exp Clin Transplant

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Objectives: Human leukocyte antigen alloimmunization is caused by exposure to HLA antigens through transfusion, pregnancy, or transplant. Our study objective was to present the rate of positivity of anti-HLA antibody considering the effects of a single sensitization event in kidney transplant candidates at our center. Materials and Methods: Our study reviewed 606 kidney transplant candidates. Patient sera were analyzed using Luminex xMAP technology. Panel reactive antibody positivity rates and antibody strengths in patients were analyzed according to a single sensitization event. Results: Our findings showed 246 patients (40.6%) with a panel reactive antibody > 0, of which 97 (39.4%) were sensitized from a single event, 119 (48.4%) were sensitized by multiple events, and 30 (12.2%) had no known sensitizing event. Considering patients sensitized by a single event with a panel reactive antibody > 0, we found that 25.8% had received transplant only, 49.5% had previous pregnancy only, and 24.7% had received transfusion only. The strength of antibodies was significantly higher in patients with previous transplant procedures than in those with transfusion for HLA-A (P < .01), HLA-B (P < .05), HLA-C (P < .05), HLA-DR (P < .001), HLA-DQ (P < .05), and HLA-DP (P < .05). Similarly, we observed significantly higher median fluorescence intensity values for HLA-A, -DR, -DQ, and -DP loci in patients with a previous transplant procedure versus preg nancy. The strength of antibodies against HLA-DR was significantly higher in patients with a previous pregnancy compared with those with transfusion (P < .01). Conclusions: This study documents the profile of HLA alloimmunization in kidney transplant candidates. In particular, transplant procedures appear to have a greater immunologic impact, followed by pregnancy and transfusion. Our data confirm and are in accordance with those of several studies in which the sensitization events were associated with higher prevalence of anti-HLA antibodies.

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Section: Discussionsupporting

confidence: 92%

Untitled

Resse¹,

Paolillo²,

Minucci³

et al. 2018

Exp Clin Transplant

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“…First, only the AARs accessible to antibodies that reside in α-helical coils and β-loops are considered. In contrast, the triplets that are located in the β-pleated floor and beneath the α-chains are not available for antibody binding and are often not critical for antibody production because they are not immunogenic [140][141][142][143] . Second, alloantibodies can be produced only against non-self-mismatched triplets.…”

Section: Sa Sp Luminex-based Methodology and Structural Analysis Of Hmentioning

confidence: 99%

“…The identification of immunogenic epitopes significantly affects the prediction of post-transplant alloantibody specificities, donor selection, graft outcome, and organ allocation. The recent studies of Zeevi et al [142] and Duquesnoy et al [143] used monoclonal antibodies to demonstrate the anti-HLA antibody complement-fixing abilities strictly depend on the configuration of the critical contact eplet(s) [140,141] . The results of their studies indicated that complete complement cascade activation is determined by the energy produced from the antibody-HLA interaction.…”

Section: å Eplet 167esmentioning

confidence: 99%

Methodological aspects of anti-human leukocyte antigen antibody analysis in solid organ transplantation

Lobashevsky¹

2014

WJT

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Donor human leukocyte antigen (HLA)-specific antibodies (DSA) play an important role in solid organ transplantation. Preexisting IgG isotype DSA are considered a risk factor for antibody mediated rejection, graft failure or graft loss. The post-transplant development of DSA depends on multiple factors including immunogenicity of mismatched antigens, HLA class Ⅱ typing of the recipient, cytokine gene polymorphisms, and cellular immunoregulatory mechanisms. De novo developed antibodies require special attention because not all DSA have equal clinical significance. Therefore, it is important for transplant clinicians and transplant immunologists to accurately characterize DSA. In this review, the contemporary immunological techniques for detection and characterization of anti-HLA antibodies and their pitfalls are described.

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“…A particular HLA mismatch may have many potential antibody epitopes in one patient and no foreign epitopes in another patient. The HLAMatchmaker algorithm developed by Rene Duquesnoy in Pittsburgh in close collaboration with the group in Leiden has been instrumental for the identification of the most important antibody epitopes [28][29][30][31]. Preliminary data show that donor kidneys with mismatched HLA antigens in the absence of foreign epitopes for the recipient will not induce antibodies and have a similar graft survival as fully HLA matched grafts.…”

Section: B Cell Recognition Of Donor Hla Class-i Epitopesmentioning

confidence: 99%

“…Although these polymorphisms have been linked to clinical prognosis in different clinical settings, such as chronic rejection after lung transplantation, they have not been systematically studied in kidney transplantation. Finally, more recent insights have indicated that epitope matching between donor and recipient can also be used to prevent HLA-immunization [28][29][30][31][32]. However, is not clear which B or T cell epitope mismatches are associated with an increased risk for renal allograft rejection and whether the same ones are relevant in unimmunized versus highly-immunized patients.…”

Section: Introductionmentioning

confidence: 99%