Predicting Humoral Alloimmunity from Differences in Donor and Recipient HLA Surface Electrostatic Potential
| Autor: | Matthew Robb, Craig J. Taylor, Dieter Kabelitz, Eva Ellinghaus, Christiane Kling, Dermot Mallon, J. Andrew Bradley, Vasilis Kosmoliaptsis |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Graft Rejection Male medicine.medical_specialty Isoantigens Immunology Static Electricity Histocompatibility Testing Human leukocyte antigen 030230 surgery Organ transplantation 03 medical and health sciences 0302 clinical medicine Isoantibodies HLA-DQ Antigens Novel Immunological Methods Immunology and Allergy Medicine Humans Kidney transplantation business.industry Alloimmunity Donor Lymphocytes medicine.disease Kidney Transplantation Tissue Donors Transplant Recipients 3. Good health Histocompatibility Immunity Humoral Transplantation 030104 developmental biology Female business HLA-DRB1 Chains |
| Zdroj: | The Journal of Immunology Author Choice |
| ISSN: | 1550-6606 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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