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
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