Journal article
Peripheral donor specific antibodies are associated with histology and cellular subtypes in protocol liver biopsies of pediatric recipients.
- Cousin VL Swiss Pediatric Liver Center, Geneva University Hospitals, Switzerland.
- Rougemont AL Division of Clinical Pathology, Geneva University Hospitals, Switzerland.
- Rubbia-Brandt L Division of Clinical Pathology, Geneva University Hospitals, Switzerland.
- Wildhaber BE Swiss Pediatric Liver Center, Geneva University Hospitals, Switzerland.
- Villard J Department of Pathology and Immunology, University of Geneva.
- Ferrari-Lacraz S Department of Pathology and Immunology, University of Geneva.
- McLin VA Swiss Pediatric Liver Center, Geneva University Hospitals, Switzerland.
- 2020-01-03
Published in:
- Transplantation. - 2019
English
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 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 (44) 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.
CONCLUSION
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.
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 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 (44) 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.
CONCLUSION
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.
- Language
-
- English
- Open access status
- closed
- Identifiers
-
- DOI 10.1097/TP.0000000000003099
- PMID 31895340
- Persistent URL
- https://sonar.ch/global/documents/216593
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