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EP-4740023-A1 - USE OF SOLUBLE CD46 CONCENTRATION FROM PERIPHERAL BLOOD AS A PARAMETER FOR THE DIAGNOSIS OF NON-ALCOHOLIC FATTY LIVER DISEASE

EP4740023A1EP 4740023 A1EP4740023 A1EP 4740023A1EP-4740023-A1

Abstract

The present invention refers to a method of diagnosing a subject with non-alcoholic fatty liver disease (NAFLD), the method comprising determining a soluble CD46 (sCD46) concentration in a peripheral blood (PB) sample obtained from a subject, wherein said sCD46 concentration is indicative for whether or not said subject suffers from NAFLD. In addition, the present invention also relates to a data processing system comprising a processor configured to perform a method comprising the steps of obtaining a determined sCD46 concentration from a PB sample obtained from, a subject, comparing said sCD46 concentration with a cut-off value and then indicating whether or not said subject suffers from NAFLD.

Inventors

  • WERNER, Jens M.
  • BITTERER, Florian
  • Hutchinson, James Alexander

Assignees

  • Universität Regensburg, in Vertretung des Freistaats Bayern

Dates

Publication Date
20260513
Application Date
20240703

Claims (18)

  1. 1. A method of diagnosing a subject with non-alcoholic fatty liver disease (NAFLD), the method comprising determining a soluble CD46 (sCD46) concentration in a peripheral blood (PB) sample obtained from a subject, wherein said sCD46 concentration is indicative for whether or not said subject suffers from NAFLD.
  2. 2. The method of claim 1, wherein said PB sample is a plasma or a serum sample.
  3. 3. The method of claim 1 or 2, wherein said sCD46 concentration is detected using any one of an enzyme-linked immunosorbent assay (ELISA), a bead-based sandwich assay, a flow cytometry-based competitive binding assay or an immunoturbidimetric assay.
  4. 4. The method of claim 3, wherein a binding partner for sCD46 is used.
  5. 5. The method of claim 4, wherein said binding partner is any one of an immunoglobulin or a fragment thereof, a proteinaceous binding molecule with immunoglobulin-like functions, or a recombinant receptor.
  6. 6. The method of any one of claims 1-5, wherein said subject is a human.
  7. 7. The method of any one of claims 1-6, wherein said subject is an adult.
  8. 8. The method of any one of claims 1-7, wherein said subject is suspected to suffer from NAFLD.
  9. 9. The method of any one of claims 1-7, wherein said subject is suspected to be a liver transplant donor.
  10. 10. The method of any one of claims 1-9, the method further comprising comparing said sCD46 concentration determined in said PB sample with a cut-off value.
  11. 11. The method of claim 10, wherein if said sCD46 concentration is equal or above said cut- off value, it is indicative for whether said subject suffers from NAFLD.
  12. 12. The method of any one of claims 10-11, wherein said cut-off value is in the range between 43 ng/ml and 47 ng/ml.
  13. 13. The method of claim 12, wherein said cut-off value is about 45 ng/ml.
  14. 14. A data processing system comprising a processor configured to perform a method comprising the steps of a) obtaining a determined soluble CD46 (sCD46) concentration from a peripheral blood (PB) sample obtained from a subject; b) comparing said sCD46 concentration obtained in step a) with a cut-off value; c) indicating whether or not said subject suffers from non-alcoholic fatty liver disease (NAFLD).
  15. 15. The data processing system of claim 14, the method further comprising indicating whether said subject suffers from NAFLD, if said sCD46 concentration is equal or above said cut- off value.
  16. 16. A device capable of detecting a soluble CD46 (sCD46) concentration in a peripheral blood (PB) sample obtained from a subject, comprising the data processing system of any one of claims 14-15.
  17. 17. A computer program comprising instructions to cause the data processing system of any one of claims 14-15 or the device of claim 16 to execute the steps of a) obtaining a determined soluble CD46 (sCD46) concentration from a peripheral blood (PB) sample obtained from a subject; b) comparing said sCD46 concentration obtained in step a) with a cut-off value; c) indicating whether or not said subject suffers from non-alcoholic fatty liver disease (NAFLD).
  18. 18. A computer-readable medium having stored thereon the computer program of claim 17.

Description

USE OF SOLUBLE CD46 CONCENTRATION FROM PERIPHERAL BLOOD AS A PARAMETER FOR THE DIAGNOSIS OF NON-ALCOHOLIC FATTY LIVER DISEASE. CROSS-REFERENCE TO RELATED APPLICATIONS The present application claims the benefit of priority of EP Patent Application No. 23183382.3 filed 04 July 2023, the content of which is hereby incorporated by reference in its entirety for all purposes. HELD OF THE INVENTION [001] The present invention refers to a method of diagnosing a subject with non-alcoholic fatty liver disease (NAFLD), the method comprising determining a soluble CD46 (sCD46) concentration in a peripheral blood (PB) sample obtained from a subject, wherein said sCD46 concentration is indicative for whether or not said subject suffers from NAFLD. In addition, the present invention also relates to a data processing system comprising a processor configured to perform a method comprising the steps of obtaining a determined sCD46 concentration from a PB sample obtained from a subject, comparing said sCD46 concentration with a cut-off value and then indicating whether or not said subject suffers from NAFLD. BACKGROUND OF THE INVENTION [002] Nonalcoholic fatty liver disease (NAFLD) has become one of the most common causes of liver diseases worldwide. Owing to the increasing prevalence of obesity and metabolic syndrome, NAFLD is becoming a greater clinical challenge because of no existing therapy and a lack of biomarkers. (003) Excessive deposition of fat as triglycerides in the liver forms lipid droplets within hepatocytes, a pathological condition known as hepatic steatosis which is an evidence of NAFLD (Wang, K. Expert Rev Mol Med 18, el4 (2016)). Hepatic steatosis often reflects a chronic imbalance between, on the one hand, hepatic fatty acid uptake and triglyceride synthesis, and on the other, triglyceride metabolism and excretion (Kawano, Y. & Cohen, D.E. J Gastroenterol 48, 434-441 (2013)). Steatosis itself is not harmful and can usually be reversed by treating the underlying cause; however, triglyceride deposition causes oxidative stress to hepatocytes, which ultimately leads to chronic inflammation of the liver (Ertunc, M.E. & Hotamisligil, G.S. J Lipid Res 57, 2099-2114 (2016)). [004] Such inflammatory changes of fat deposition can lead to a liver inflammation (short: steatohepatitis), which is determined as non-alcoholic steatohepatitis (short: NASH) within NAFLD. In some individuals, this NASH may even drive hepatic fibrosis, which can eventually progress to cirrhosis and hepatocellular carcinoma. [005] Currently, no pharmacological therapy is available to treat NAFLD. The reason might be that NAFLD is a multi-factorial disease with an incomplete understanding of the mechanisms involved, an absence of accurate and inexpensive imaging tools, and lack of adequate non- invasive or less invasive biomarker. Thus, at present a diagnosis of NAFLD is for example possible by applying an invasive liver biopsy. Mostly, such biopsies are performed these days if the patient simultaneously suffers from a liver tumor which will then also be removed surgically. Thus, NAFLD is only diagnosed in an advanced stage. [006] Accordingly, there is a need to provide a new method of diagnosing NAFLD. The solution of the present invention is described in the following, exemplified in the appended examples, illustrated in the figures and reflected in the claims. SUMMARY OF THE INVENTION [007] The present inventors have found a less invasive and less expensive, but still accurate method of diagnosing NAFLD based on a simple blood test whereby a soluble CD46 (sCD46) concentration in a peripheral blood (PB) sample from a subject is detected. With the method of the invention it is now possible to avoid invasive methods comprising obtaining liver tissue biopsies from a subject who is suffering from NAFLD and examining those as known by the skilled person or examining the liver with challenging imaging tools such as MRT and/or ultrasound. [008] Of immediate clinical relevance, sCD46 concentration in the PB, preferably in the plasma, performed extremely well as a predictive biomarker for steatosis grade, wherein a subject can be classified as non-steatotic or steatotic based on such steatosis grades as defined elsewhere herein which then allows to diagnose a subject with NAFLD or not. Thus the inventors found out a correlation of the steatosis grade as defined elsewhere herein and the sCD46 concentration in the PB. Therefore, it was concluded that there is great promise in sCD46 as biomarker in a less-invasive method for diagnosing NAFLD in a subject. [009] Accordingly, in a first aspect, the present invention relates to a method of diagnosing a subject with NAFLD, the method comprising determining a sCD46 concentration in a PB sample obtained from a subject, wherein said sCD46 concentration is indicative for whether or not said subject suffers from NAFLD. [0010] In a second aspect, the present invention relates to a data processing system compri