Peripheral Donor-specific Antibodies Are Associated With Histology and Cellular Subtypes in Protocol Liver Biopsies of Pediatric Recipients
Autor: | Anne-Laure Rougemont, Vladimir L. Cousin, Laura Rubbia-Brandt, Jean Villard, Valérie A. McLin, Sylvie Ferrari-Lacraz, Barbara E. Wildhaber |
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Rok vydání: | 2020 |
Předmět: |
Graft Rejection
Male Pathology Histocompatibility Testing/statistics & numerical data Biopsy T-Lymphocytes medicine.medical_treatment Isoantibodies/analysis/immunology Macrophages/immunology ddc:616.07 Liver Transplantation/adverse effects 030230 surgery Liver transplantation Severity of Illness Index Graft Rejection/immunology/pathology 0302 clinical medicine HLA Antigens Isoantibodies Fibrosis Living Donors End Stage Liver Disease/diagnosis/etiology/surgery Child ddc:616 CD20 Graft Survival/immunology Immunity Cellular ddc:618 medicine.diagnostic_test biology Histocompatibility Testing Graft Survival Transplant Recipients/statistics & numerical data Allografts Cellular Infiltrate Living Donors/statistics & numerical data Portal System Liver Child Preschool Female 030211 gastroenterology & hepatology HLA Antigens/immunology medicine.symptom Adult medicine.medical_specialty Adolescent Homologous/adverse effects Inflammation Portal System/cytology/immunology End Stage Liver Disease Young Adult 03 medical and health sciences medicine Humans Transplantation Homologous Preschool Transplantation business.industry Macrophages Immunity Infant T-Lymphocytes/immunology medicine.disease Transplant Recipients Liver Transplantation Allografts/blood supply/immunology/pathology biology.protein Cellular business Liver/blood supply/immunology/pathology CD8 Follow-Up Studies |
Zdroj: | Transplantation, Vol. 104, No 8 (2020) pp. 1633-1643 |
ISSN: | 0041-1337 |
DOI: | 10.1097/tp.0000000000003099 |
Popis: | Background The cellular infiltrate in protocol liver biopsies (PB) following pediatric liver transplantation remains mostly uncharacterized, yet there is increasing concern about the role of inflammation and fibrosis in long-term liver allografts. We aimed to define cell types in PB and to analyze their relationship with donor-specific antibodies (DSA) and histological phenotype. Methods PB were performed at least 1 year after transplantation. We identified 4 phenotypes: normal, fibrosis, inflammation, inflammation with fibrosis. Cell types were counted after immunostaining for CD3, CD4, CD8, CD68, CD20, MUM1, and FoxP3. Results Forty-four patients underwent 1 PB between 2000 and 2015. Eleven percent (5/44) of PB displayed normal histology, 13.6% (6/44) fibrosis, 34.1% (15/44) inflammation, and 40.9% (18/44) inflammation and fibrosis. The main cell types in the portal tracts and lobules were CD3+ and CD68+ cells. Frequency of de novo DSA was 63% (27/44). The presence of CD8+ cells in the lobules was associated with fibrosis. Inflammation and fibrosis in PB were associated with the presence of circulating de novo DSA, number of de novo DSA, and C1q binding activity when compared to other phenotypes. Conclusions T cells (CD3+) and macrophages (CD68+) were the most prevalent cell-types in PB. In the presence of inflammation, portal tracts were enriched in CD3+, CD20+ but displayed fewer CD68+. This coincided with the presence and number of de novo DSA. How these cellular and humoral actors interact is unclear, but peripheral DSA may be a marker of immune cellular activity in the seemingly quiescent allograft. |
Databáze: | OpenAIRE |
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