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Predicting Humoral Alloimmunity from Differences in Donor and Recipient HLA Surface Electrostatic Potential.
Mallon, Dermot H; Kling, Christiane; Robb, Matthew; Ellinghaus, Eva; Bradley, J Andrew; Taylor, Craig J; Kabelitz, Dieter; Kosmoliaptsis, Vasilis.
Afiliação
  • Mallon DH; Department of Surgery, University of Cambridge, Addenbrooke's Hospital, Cambridge CB2 0QQ, United Kingdom.
  • Kling C; National Institute for Health Research Blood and Transplant Research Unit in Organ Donation and Transplantation, University of Cambridge, Cambridge CB2 0QQ, United Kingdom.
  • Robb M; National Institute of Health Research Cambridge Biomedical Research Centre, Cambridge CB2 0QQ, United Kingdom.
  • Ellinghaus E; Institute for Immunology, University Medical Centre Schleswig-Holstein, Kiel University, 24105 Kiel, Germany.
  • Bradley JA; Statistics and Clinical Studies Unit, National Health Service Blood and Transplant, Bristol BS34 7QH, United Kingdom.
  • Taylor CJ; Institute of Clinical Molecular Biology, University Medical Centre Schleswig-Holstein, Kiel University, 24105 Kiel, Germany; and.
  • Kabelitz D; Department of Surgery, University of Cambridge, Addenbrooke's Hospital, Cambridge CB2 0QQ, United Kingdom.
  • Kosmoliaptsis V; National Institute for Health Research Blood and Transplant Research Unit in Organ Donation and Transplantation, University of Cambridge, Cambridge CB2 0QQ, United Kingdom.
J Immunol ; 201(12): 3780-3792, 2018 12 15.
Article em En | MEDLINE | ID: mdl-30429288
ABSTRACT
In transplantation, development of humoral alloimmunity against donor HLA is a major cause of organ transplant failure, but our ability to assess the immunological risk associated with a potential donor-recipient HLA combination is limited. We hypothesized that the capacity of donor HLA to induce a specific alloantibody response depends on their structural and physicochemical dissimilarity compared with recipient HLA. To test this hypothesis, we first developed a novel computational scoring system that enables quantitative assessment of surface electrostatic potential differences between donor and recipient HLA molecules at the tertiary structure level [three-dimensional electrostatic mismatch score (EMS-3D)]. We then examined humoral alloimmune responses in healthy females subjected to a standardized injection of donor lymphocytes from their male partner. This analysis showed a strong association between the EMS-3D of donor HLA and donor-specific alloantibody development; this relationship was strongest for HLA-DQ alloantigens. In the clinical transplantation setting, the immunogenic potential of HLA-DRB1 and -DQ mismatches expressed on donor kidneys, as assessed by their EMS-3D, was an independent predictor of development of donor-specific alloantibody after graft failure. Collectively, these findings demonstrate the translational potential of our approach to improve immunological risk assessment and to decrease the burden of humoral alloimmunity in organ transplantation.
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Antígenos HLA-DQ / Transplante de Rim / Imunidade Humoral / Cadeias HLA-DRB1 / Rejeição de Enxerto / Isoanticorpos / Isoantígenos Tipo de estudo: Diagnostic_studies / Prognostic_studies / Risk_factors_studies Limite: Female / Humans / Male Idioma: En Revista: J Immunol Ano de publicação: 2018 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Antígenos HLA-DQ / Transplante de Rim / Imunidade Humoral / Cadeias HLA-DRB1 / Rejeição de Enxerto / Isoanticorpos / Isoantígenos Tipo de estudo: Diagnostic_studies / Prognostic_studies / Risk_factors_studies Limite: Female / Humans / Male Idioma: En Revista: J Immunol Ano de publicação: 2018 Tipo de documento: Article