Antibody-mediated rejection owing to donor-specific HLA-DQA1 antibodies after renal transplantation: A case report |
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| Institution: | 1. Department of Blood Transfusion, Tianjin First Central Hospital, School of Medicine, Nankai University, Tianjin, China;2. Department of Pathology, Tianjin First Central Hospital, School of Medicine, Nankai University, Tianjin, China;2. NHC Key Laboratory of Cell Transplantation, 23 Youzheng Street, Nangang District, Harbin, Heilongjiang Province, 150001, China;1. Medical Sciences Institute, Blood Center of Wisconsin, Department of Pathology, Medical College of Wisconsin, Milwaukee, WI, USA;2. Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA, USA;3. Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, USA;1. Department of Cardiac Surgery and Vascular Surgery, Medical University of Gdansk, Mariana Smoluchowskiego 17, 80-214 Gdańsk, Poland;2. Department of Clinical Immunology and Transplantology, Medical University of Gdansk, Dębinki 7, 80-211 Gdańsk, Poland;3. Immunology & Transplantology Clinical Laboratory, University Laboratory Medicine Centre, University Clinical Center in Gdańsk, Dębinki 7, 80-211 Gdańsk, Poland;4. Department of Histology, Institute of Medical Sciences, University of Opole, Oleska 48, 45-052 Opole, Poland;5. Medical University of Gdansk (student), M. Sklodowskiej-Curie 3a, 80-210 Gdańsk, Poland;6. Department of Gastroenterology and Hepatology, Medical University of Gdansk, Mariana Smoluchowskiego 17, 80-214 Gdańsk, Poland;7. Department of Pneumonology and Allergology, Medical University of Gdansk, Mariana Smoluchowskiego 17, 80-214 Gdańsk, Poland;1. Immunology Service, University Hospital Marqués de Valdecilla-IDIVAL, University of Cantabria, Santander, Spain;2. Nephrology Service, University Hospital Marqués de Valdecilla-IDIVAL, University of Cantabria, Santander, Spain;3. Nephrology Service, Donostia Ospitalea-Hospital Universitario de Donostia, San Sebastián, Spain;4. Department of Clinical Biochemistry, University Hospital Marqués de Valdecilla- IDIVAL, University of Cantabria, Santander, Spain;5. Pathology Service, University Hospital Marqués de Valdecilla-IDIVAL, University of Cantabria, Santander, Spain |
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| Abstract: | BackgroundDonor-specific HLA antibodies are important risk factors in antibody-mediated rejection and graft loss after renal transplantation and are associated with higher rejection rates and lower graft survival. Most de novo donor specific antibodies (dnDSA) after renal transplantation are directed toward donor HLA-DQ antigens. An HLA-DQ antigen is a heterodimer consisting of an alpha and beta chain. Traditionally, HLA-DQA1 typing has not been part of pretransplant evaluation. Therefore, DQ alpha proteins are not usually considered in the interpretation of HLA-DQ antibody reactions.MethodsThe renal transplant recipient had a 0% panel reactive antibody pretransplant. Two years after transplantation, he developed symptoms of abdominal distension and bilateral lower extremity edema. Histopathological findings on renal puncture biopsy showed a combination of T-cell-mediated acute rejection type IIA and antibody-mediated rejection with a trend toward chronicity in the transplanted kidney. DSAs were investigated by HLA-I (HLA-A/B) and HLA-II (HLA-DRB1/DQA1/DQB1) single antigen bead (SAB) assay. HLA typing was performed to explain the antibody reactivity patterns by PCR-SSO and Sequencing-based typing (SBT). HLAMatchmaker analysis was performed to identify eplets that explain antibody reactivity patterns.ResultsHLA-II SAB analysis of the patient's serum at the time of rejection showed positive reactions with all DQB1*03:03-carrying beads with high mean fluorescence intensity (MFI). However, DQB1*03:03 was not a dnDSA antigen. High-resolution HLA typing revealed that HLA-DQA1*05:01 and DQA1*03:02 were mismatched donor antigens. HLA Matchmaker analysis demonstrated reactivity toward 130R and 116 V eplet on DQA1 and DQB1.ConclusionsAntibodies specific to DQα chains after renal transplantation were highlighted. |
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