Non-invasive screening for subclinical liver graft injury in adults via donor-specific anti-HLA antibodies

Autor: Björn Hartleben, Michael Hallensleben, Michael P. Manns, Danny Jonigk, Anne Höfer, Murielle Verboom, Elmar Jaeckel, Richard Taubert
Rok vydání: 2020
Předmět:
0301 basic medicine
Graft Rejection
Male
medicine.medical_treatment
Biopsy
lcsh:Medicine
Translational immunology
Gastroenterology
0302 clinical medicine
Fibrosis
HLA Antigens
Isoantibodies
lcsh:Science
Subclinical infection
Multidisciplinary
medicine.diagnostic_test
biology
Graft Survival
Immunosuppression
Middle Aged
Allografts
Tissue Donors
Liver
Liver biopsy
Female
medicine.symptom
Antibody
Adult
medicine.medical_specialty
Inflammation
Article
03 medical and health sciences
Young Adult
Internal medicine
medicine
Humans
Aged
Retrospective Studies
Immunosuppression Therapy
Keratin-18
Hepatology
business.industry
lcsh:R
medicine.disease
Peptide Fragments
Liver Transplantation
Liver graft
Transplantation
body regions
030104 developmental biology
biology.protein
lcsh:Q
business
030217 neurology & neurosurgery
Biomarkers
Zdroj: Scientific Reports
Scientific Reports, Vol 10, Iss 1, Pp 1-12 (2020)
ISSN: 2045-2322
Popis: The majority of liver grafts exhibit abnormal histological findings late after transplantation, even when liver enzymes are normal. Such subclinical graft injuries were associated with rejection and fibrosis progression in recent studies. The identification of non-invasive biomarkers for subclinical graft injury might help to individualize immunosuppression. Therefore, graft injury was assessed in 133 liver biopsies with normal/near normal liver enzymes from a prospective liver biopsy program. Cytokeratin-18 cell death marker (M65) and donor specific anti-HLA antibodies (DSA) were measured as non-invasive markers in paired plasma samples in addition to routine parameters. M65 was associated with subclinical graft injury but this association was too weak for reasonable clinical application. DSA positivity was associated with more graft inflammation (OR = 5.4) and more fibrosis (OR = 4.2). Absence of DSA excluded fibrosis in 87–89%, while presence of DSA excluded histological criteria for immunosuppression minimization attempts in 92–97%. While CK18 cell death marker had no diagnostic value for the detection of subclinical liver graft injury, DSA testing can help to preselect patients for immunosuppression reduction in case of DSA negativity, while DSA positivity should prompt elastography or liver biopsy for the assessment of subclinical graft injury.
Databáze: OpenAIRE
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