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Appearance of new CDC-reactive antibodies in patients waiting for kidney transplantation
Institution:1. Institute for Transfusion Medicine, University Hospital of Schleswig-Holstein, Lübeck, Germany;2. Transplant center, University Hospital of Schleswig-Holstein, Lübeck, Germany;3. Transplant center, University Hospital of Schleswig-Holstein, Kiel, Germany;1. Division of Gastroenterology and Transplantation Institute, Loma Linda University Health, Loma Linda, CA, United States of America;2. Department of Pathology, Molecular and Cell Medicine, Icahn School of Medicine at Mount Sinai, United States of America;3. Recanati/Miller Transplantation Institute, Division of Liver Diseases, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, United States of America;1. National Clinical Research Center of Kidney Diseases, Jinling Hospital, Nanjing University School of Medicine, Nanjing, 210002, China;2. AlloDx Biotech Co, Ltd, Shanghai, 201100, China;3. Institute of Life Sciences, Jiangsu University, Zhenjiang, 212013, China;1. Baskent University Pediatric Nephrology, Ankara, Turkey;2. Baskent University Pathology, Ankara, Turkey;3. Baskent University General Surgery, Ankara, Turkey;1. Department. of Hematology and Oncology, Children''s Hospital, Los Angeles, CA 90027, United States of America;2. Division of Nephrology, Dept. of Medicine, Sidney Kimmel Medical College at Thomas Jefferson University, Philadelphia, PA 19145, United States of America;3. Department of Immunology and Microbial Pathogenesis, West Virginia University, School of Medicine, Morgantown, WV 26506, United States of America;4. Health Sciences Research Center (CICS-UBI) & Department of Medical Sciences, University of Beira Interior, Covilhã 6200-506, Portugal;5. Department of Pathology, SUNY Downstate Health Sciences University, Brooklyn, NY 11203, United States of America;6. Department of Medicine and Cell Biology, Transplant Immunology and Immunogenetics, SUNY Downstate Health Sciences University, Brooklyn, NY 11203, United States of America
Abstract:BackgroundPatients awaiting kidney transplantation are regularly screened for HLA-antibodies, but there is scarce data about the optimal interval.MethodsResults from Complement-dependent cytotoxicity testing (CDC) for waitlisted patients were reviewed for increases in panel reactive antibodies (PRA) by at least 10%-points. Clinical records were screened for historic immunizing events and possible trigger factors preceding the PRA-increase. Additionally, non-pretransplanted men tested negative for HLA antibodies by solid-phase assays (SPA) out of their first two samples on the waiting list (“non-immunized men”) were evaluated for detection of HLA antibodies by SPA during their further stay on the waiting list.Results15,360 samples from 1928 patients tested by CDC were analyzed for changes in PRA. PRA-increases occurred most frequently in patients waitlisted recently for retransplantation (annual incidence 6%). Removal of previous transplants, severe infections and/or reduced immunosuppression triggered 65% of PRA-increases during the first year after waitlisting. Transfusions accounted for 55% of PRA-increases in later years. Leucocyte-reduced red blood cell units not only boosted historic antibodies, but even induced primary immunization. In the second part of the study, 6780 samples tested by SPA from 703 non-immunized men were evaluated for development of HLA-antibodies. Only 9 men (1.3%) turned HLA antibody-positive (annual incidence 0.4%).ConclusionA uniform screening interval does not fit all: Frequencies should be highest in patients newly waitlisted for re-transplant and lowest in non-immunized men. Transfused patients should be monitored closely for development of HLA-antibodies even if leukoreduced products are used.
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