Albumin transport function analysis by EPR spectroscopy
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Albumin transport function analysis by EPR spectroscopy is an in vitro blood test that detects changes to the transport and molecular conformation of serum albumin using the method of EPR spectroscopy. The test is used for diagnosis of cancer, sepsis and toxemia.
Principles
[edit]The test is based on the interaction of spin-labeled fatty acids with serum albumin by means of EPR spectroscopy.[1][2][3]
A sample of blood serum is subjected to a spin probe 16-doxyl stearate. Spin probe molecules bind specifically to albumin molecules where they occupy two main positions:
- primary binding sites located in albumin domains, where their mobility is restricted
- the relatively spacious hydrophobic area between the protein domains in the interior of the albumin globule.
The spin probe molecules bound on albumin have restricted mobility that changes the EPR spectrum, which reflects characteristics of the protein site where the spin probe is located and allows estimating the conformation of the albumin globule. Some part of the spin probe remains in the serum in the unbound state. The ratio of the fractions of bound and unbound spin probes allows estimating the functional activity of albumin molecules. Analysis of the EPR spectrum allows assessment of the conformation and functional activity of albumin molecules.
The test material is 100 μL serum or plasma.
The procedure includes mixing a serum sample with a spin probe reagent, incubating the mixture, measuring the EPR spectrum of a serum with a spin probe, and analyzing the EPR spectrum by calculating the conformation and functional indicators of albumin molecules.
Applications
[edit]Cancer diagnosis
[edit]A specific change to the conformation of albumin molecules[4][5] that is associated with the growth of a malignant tumor is caused by (or associated with) changes in the composition of metabolites carried by serum albumin during the growth of a malignant tumor[6][7] (proliferating cancer cells uptake and release metabolites in abnormal quantities).
Clinical studies of the EPR test of serum albumin[8][9][10][11][12] showed diagnostic sensitivity and specificity of 90%.
Clinical applications:
- as a screening test to detect cancer-specific metabolic alterations in patients;
- to determine whether the cancer growth has stopped or the disease is progressing;
- to determine when cancer treatment is effective or needs to be changed.
Sepsis and toxemia
[edit]Reduced functional activity of serum albumin (reduced binding efficacy) is associated with toxemia (an increase in the concentration of toxic molecules in the blood) and is manifested before other clinical symptoms.
Clinical applications:
- prognosis and early diagnosis of sepsis (1 to 2 hours after surgery);[13]
- diagnosis of severe preeclampsia (gestosis) in women in the 2nd and 3rd trimesters of pregnancy;[14]
- diagnostics of the functional status of a kidney transplant[3][14][15]
- early diagnosis of congenital pneumonia in newborns.
References
[edit]- ^ Kristina Boss, Katja Waterstradt, Kerstin Schnurr (2023-10-29). "Binding and detoxification efficiency of albumin decline after haemodialysis". Nephrology, Dialysis, Transplantation: gfad133. doi:10.1093/ndt/gfad133. PMC 10828194. PMID 37558390.
{{cite journal}}: CS1 maint: multiple names: authors list (link) - ^ Klinkmann, Gerd; Waterstradt, Katja; Klammt, Sebastian; Schnurr, Kerstin; Schewe, Jens-Christian; Wasserkort, Reinhold; Mitzner, Steffen (2023). "Exploring Albumin Functionality Assays: A Pilot Study on Sepsis Evaluation in Intensive Care Medicine". International Journal of Molecular Sciences. 24 (16): 12551. doi:10.3390/ijms241612551. PMC 10454468. PMID 37628734.
- ^ a b Kalachyk, A.; Ugolev, I.; Zabello, T.; Voitovich, V. (2014). "Electron Spin Resonance Spectroscopy of Albumin Transport Quality Is a New Test for Diagnosis of Kidney Transplant Acute Rejection.: Abstract# A232". Transplantation. 98: 466. doi:10.1097/00007890-201407151-01549. ISSN 0041-1337.
- ^ V.Muravsky; A.Gurachevsky; G.Matthes (2007). "Disease-specific albumin patterns defined by electron spin resonance". Tumor Biol. 28 (suppl. 1). ISSN 1423-0380.
- ^ Kazmierczak, S. C.; Gurachevsky, A.; Matthes, G.; Muravsky, V. (2006-09-21). "Electron Spin Resonance Spectroscopy of Serum Albumin: A Novel New Test for Cancer Diagnosis and Monitoring". Clinical Chemistry. 52 (11): 2129–2134. doi:10.1373/clinchem.2006.073148. ISSN 0009-9147. PMID 16990414.
- ^ Lance A. Liotta; Emanuel F. Petricoin; David A. Fishman; Vincent Fusaro; Mark S. Lowenthal; Sally Ross (2003). "Biomarker Amplification by Serum Carrier Protein Binding". Disease Markers. 19 (1): 1–10. doi:10.1155/2003/104879. PMC 3851653. PMID 14757941.
- ^ Lowenthal, M. S. (2005-10-01). "Analysis of Albumin-Associated Peptides and Proteins from Ovarian Cancer Patients". Clinical Chemistry. 51 (10): 1933–1945. doi:10.1373/clinchem.2005.052944. ISSN 0009-9147. PMID 16099937.
- ^ Seidel P, Gurachevsky A, Muravsky V, Schnurr K, Seibt G, Matthes G (2005). "Recognition of malignant processes with neural nets from ESR spectra of serum albumin". Z. Med. Phys. 15 (4): 265–272. doi:10.1078/0939-3889-00263. PMID 16422355.
- ^ Gurachevsky, Andrey; Muravskaya, Ekaterina; Gurachevskaya, Tatjana; Smirnova, Lena; Muravsky, Vladimir (2007). "Cancer-Associated Alteration in Fatty Acid Binding to Albumin Studied by Spin-Label Electron Spin Resonance". Cancer Investigation. 25 (6): 378–383. doi:10.1080/07357900701407947. ISSN 0735-7907. PMID 17882647. S2CID 37370861.
- ^ Gelos, Marcos; Hinderberger, Dariush; Welsing, Ellen; Belting, Julia; Schnurr, Kerstin; Mann, Benno (2010). "Analysis of albumin fatty acid binding capacity in patients with benign and malignant colorectal diseases using electron spin resonance (ESR) spectroscopy". International Journal of Colorectal Disease. 25 (1): 119–127. doi:10.1007/s00384-009-0777-0. ISSN 0179-1958. PMID 19644694. S2CID 22005646.
- ^ Gurachevsky, Andrey; Kazmierczak, Steven C.; Jörres, Achim; Muravsky, Vladimir (2008-01-01). "Application of spin label electron paramagnetic resonance in the diagnosis and prognosis of cancer and sepsis". Clinical Chemistry and Laboratory Medicine. 46 (9): 1203–10. doi:10.1515/CCLM.2008.260. ISSN 1437-4331. PMID 18783341. S2CID 10982218.
- ^ Maximilian Moergel; Peer W. Kämmerer; Kerstin Schnurr; et al. (2012). "Spin electron paramagnetic resonance of albumin for diagnosis of oral squamous cell carcinoma (OSCC)". Clinical Oral Investigations. 16 (6): 1529–1533. doi:10.1007/s00784-011-0655-3. PMID 22160580. S2CID 21300133.
- ^ Vorobiev P, Bezmelnitsyna L, Krasnova L, Muravsky V, Davidova T, Sytov A (2013). "Economical Justification of the Innovation Method of Laboratory Diagnostic of the Structural and Functional Changes of Serum Albumin in Septic Complications (Ata-Test)". Value in Health. 16 (7): A364. doi:10.1016/j.jval.2013.08.242.
- ^ a b U. Muravski; A. Kalachyk; T. Ivanets (2015). "Detoxifying activity of serum albumin demonstrated diagnostic utility in patients with kidney transplant dysfunction and pregnant women with preeclampcia" (PDF).
- ^ A. Kalachyk; I. Ugolev; T. Zabello; E. Oganova; V. Muravsky (2014-01-01). "Electron spin resonance spectroscopy of serum albumin is a novel test for diagnosis of the kidney transplant acute rejection". Clinical Chemistry and Laboratory Medicine. 52 (Supplement). doi:10.1515/cclm-2014-4035. ISSN 1437-4331.