Bitterer, Florian and Kupke, Paul and Adenugba, Akinbami and Evert, Katja and Glehr, Gunther and Riquelme, Paloma and Scheibert, Lena and Preverin, Giulia and Boehm, Christina and Hornung, Matthias and Schlitt, Hans J. and Wenzel, Juergen J. and Geissler, Edward K. and Safinia, Niloufar and Hutchinson, James A. and Werner, Jens M. (2024) Soluble CD46 as a diagnostic marker of hepatic steatosis. EBIOMEDICINE, 104: 105184. ISSN 2352-3964,
Full text not available from this repository. (Request a copy)Abstract
Background The increasing prevalence of metabolic dysfunction -associated steatotic liver disease (MASLD) incurs substantial morbidity, mortality and healthcare costs. Detection and clinical intervention at early stages of disease improves prognosis; however, we are currently limited by a lack of reliable diagnostic tests for population screening and monitoring responses to therapy. To address this unmet need, we investigated human invariant Natural Killer T cell (iNKT) activation by fat -loaded hepatocytes, leading to the discovery that circulating soluble CD46 (sCD46) levels accurately predict hepatic steatosis. Methods sCD46 in plasma was measured using a newly developed immuno-competition assay in two independent cohorts: Prospective living liver donors (n = 156; male = 66, female = 90) and patients with liver tumours (n = 91; male = 58, female = 33). sCD46 levels were statistically evaluated as a predictor of hepatic steatosis. Findings Interleukin-4-secreting (IL -4 + ) iNKT cells were over -represented amongst intrahepatic lymphocytes isolated from resected human liver samples. IL -4 + iNKT cells preferentially developed in cocultures with a fat -loaded, hepatocyte-like cell line, HepaRG. This was attributed to induction of matrix metalloproteases (MMP) in fat -loaded HepaRG cells and primary human liver organoids, which led to indiscriminate cleavage of immune receptors. Loss of cell -surface CD46 resulted in unrepressed differentiation of IL -4 + iNKT cells. sCD46 levels were elevated in patients with hepatic steatosis. Discriminatory cut-off values for plasma sCD46 were found that accurately classi fi ed patients according to histological steatosis grade. Interpretation sCD46 is a reliable clinical marker of hepatic steatosis, which can be conveniently and non -invasively measured in serum and plasma samples, raising the possibility of using sCD46 levels as a diagnostic method for detecting or grading hepatic steatosis.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | FATTY LIVER-DISEASE; MEMBRANE COFACTOR PROTEIN; SIMPLE NONINVASIVE INDEX; SIGNIFICANT FIBROSIS; ACCUMULATION; ACTIVATION; IL-4; PREDICTION; MANAGEMENT; RECEPTOR; Hepatic steatosis; Fatty liver disease; Predictive marker; Innate immunity |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Chirurgie Medicine > Lehrstuhl für Medizinische Mikrobiologie und Hygiene Medicine > Lehrstuhl für Pathologie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 28 Jul 2025 11:49 |
| Last Modified: | 28 Jul 2025 11:49 |
| URI: | https://pred.uni-regensburg.de/id/eprint/63868 |
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