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Electrical and viscoelastic parameters of erythrocytes as predictors of exacerbation in inflammatory bowel diseases

https://doi.org/10.18699/SSMJ20210513

Abstract

The aim of this work is to study the electrical and viscoelastic parameters of erythrocytes for patients with inflammatory bowel diseases (IBD), examined in dynamics, as possible predictors of exacerbation of the disease. Material and methods. In dynamics, 23 patients with IBD (37.9 ± 4.3 years) were examined. The first examination was carried out in the stage of exacerbation, the second – after 6–12 months – in the stage of remission of IBD. Additionally, 36 patients with IBD in remission were examined to assess the predictive capabilities of erythrocyte parameters with subsequent monitoring of their condition for 6–12 months. The electrical and viscoelastic parameters of erythrocytes were investigated by dielectrophoresis. Statistical processing was carried out using a system of machine learning methods – Random Forest, MATLAB (R2019a, MathWorks). Results and discussion. The parameters of erythrocytes, which are predictors of exacerbation of IBD, were revealed: an increase in the proportion of deformed cells (p = 0.0001); altered nature of the erythrocyte surface (p = 0.011); increased electrical conductivity of membranes (p = 0.0019); reduced dipole moment (p = 0.0015), the rate of directional movement of erythrocytes to the electrodes (p = 0.005) (paired and unpaired Volcano plot methods), reduced deformation amplitude at a frequency of 5×105 Hz (p = 0.009), capacity of erythrocyte membranes (p = 0.029 ) (unpaired Volcano plot method). Indicators associated with changes in the charge of cells, the structure of erythrocyte membranes and the level of energy metabolism of the cell turned out to be significant. A high diagnostic accuracy of these indicators was established as predictors: the proportion of deformed cells (AUC 0.939), a summarized viscosity index (AUC 0.932). Cluster analysis of the values of erythrocyte parameters – predictors of exacerbation made it possible to stratify the risk of exacerbation: at the most altered levels of parameters – the development of exacerbation after 2.5–4.5 months, intermediate levels – after 4–6 months, minimally changed – after 8–12 months (predictive accuracy – 92 %). Conclusions. The revealed electrical and viscoelastic parameters of erythrocytes should be considered as promising predictors of exacerbation in patients with IBD.

About the Authors

M. V. Kruchinina
Research Institute of Internal and Preventive Medicine – Branch of the Institute of Cytology and Genetics SB RAS; Novosibirsk State Medical University of Minzdrav of Russia
Russian Federation

Margarita V. Kruchinina, doctor of medical sciences

630089, Novosibirsk, Boris Bogatkov str., 175/1;

630091, Novosibirsk, Krasny av., 52



I. O. Svetlova
Research Institute of Internal and Preventive Medicine – Branch of the Institute of Cytology and Genetics SB RAS; Novosibirsk State Medical University of Minzdrav of Russia
Russian Federation

Irina O. Svetlova, candidate of medical sciences

630089, Novosibirsk, Boris Bogatkov str., 175/1;

630091, Novosibirsk, Krasny av., 52



A. V. Azgaldyan
Research Institute of Internal and Preventive Medicine – Branch of the Institute of Cytology and Genetics SB RAS
Russian Federation

Alexandra V. Azgaldyan

630089, Novosibirsk, Boris Bogatkov str., 175/1



A. A. Gromov
Research Institute of Internal and Preventive Medicine – Branch of the Institute of Cytology and Genetics SB RAS
Russian Federation

Andrey A. Gromov, candidate of medical sciences

630089, Novosibirsk, Boris Bogatkov str., 175/1



V. M. Generalov
State Research Center of Virology and Biotechnology «Vector» of Rospotrebnadzor
Russian Federation

Vladimir M. Generalov, doctor of technical sciences

630559, Koltsovo, Novosibirsk region



I. N. Yakovina
Novosibirsk State Technical University
Russian Federation

Irina N. Yakovina, candidate of technical sciences

630073, Novosibirsk, Karl Marx av., 20



A. A. Shestov
University of Pennsylvania
United States

Alexander A. Shestov, candidate of chemical sciences

PA 19104, Pennsylvania, Walnut str., 3101



References

1. Golovenko O.V., Khomeriki S.G., Ivanova E.V., Fedorov E.D., Golovenko A.O. Inflammatory bowel disease. Clinical, endoscopic, morphological aspects of diagnostics. Principles of modern therapy. Moscow: Prima Print, 2017. 180 p. [In Russian].

2. Boirivant M., Leoni M., Tariciotti D., Fais S., Squarcia O., Pallone F. The clinical significance of serum C reactive protein levels in Crohn’s disease. Results of a prospective longitudinal study. J. Clin. Gastroenterol. 1988; 10: 401–405. doi: 10.1097/00004836-198808000-00011

3. Gisbert J.P., Bermejo F., Perez-Calle J.L., Taxonera C., Vera I., McNicholl A.G., Algaba A., Lopez P., Lopez-Palacios N., Calvo M., Gonzalez-Lama Y., Carneros J.A., Velasco M., Mate J. Fecal calprotectin and lactoferrin for the prediction of inflammatory bowel disease relapse. Inflamm. Bowel Dis. 2009; 15: 1190–1198. doi: 10.1002/ibd.20933

4. Chen P., Zhou G., Lin J., Li L., Zeng Z., Chen M., Zhang S. Serum biomarkers for inflammatory bowel disease. Front. Med. (Lausanne). 2020; 7: 123. doi:10.3389/fmed.2020.00123

5. Joossens S., Colombel J.F., Landers C., Poulain D., Geboes K., Bossuyt X., Targan S., Rutgeerts P., Reinisch W. Anti-outer membrane of porin C and anti-I2 antibodies in indeterminate colitis. Gut. 2006; 55: 1667–1669. doi: 10.1136/gut.2005.089623

6. Long W.Y., Chen L., Zhang C.L., Nong R.-M., Lin M.-J., Zhan L.-L., Lv X.-P. Association between NOD2/CARD15 gene polymorphisms and Crohn’s disease in Chinese Zhuang patients. World J. Gastroenterol. 2014; 20 (16): 4737–4744. doi: 10.3748/wjg.v20.i16.4737

7. Novitskiy V.V., Ryazantseva N.V., Stepovaya E.A. Physiology and pathophysiology of erythrocyte. Tomsk: Publishing House of Tomsk University, 2004. 202 p. [In Russian].

8. Dupire J., Socol M., Viallat A. Full dynamics of a red blood cell in shear flow. Proc. Natl. Acad. Sci. USA. 2012; 109 (51): 20808–20813. doi: 10.1073/pnas.1210236109

9. Generalov V.M., Kruchinina M.V., Durymanov A.G., Medvedev A.A., Safatov A.S., Sergeev A.N., Buryak G.A., Kurilovich S.A., Gromov A.A. Dielectrophoresis in the diagnosis of infectious and non-infectious diseases. Novosibirsk: TSERIS, 2011. 172 p. [In Russian].

10. Breiman L. Random Forests. Machine Learning. 2001; 45: 5–32. doi: 10.1023/A:1010933404324

11. Amre D.K., Lu S.E., Costea F., Seidman E.G. Utility of serological markers in predicting the early occurrence of complications and surgery in pediatric Crohn’s disease patients. Am. J. Gastroenterol. 2006; 101: 645–652. doi: 10.1111/j.1572-0241.2006.00468.x

12. Dubinsky M.C., Lin Y.C., Dutridge D., Picornell Y., Landers C.J., Farrior S., Wrobel I., Quiros A., Vasiliauskas E.A., Grill B., Israel D., Bahar R., Christie D., Wahbeh G., Silber G., Dallazadeh S., Shah P., Thomas D., Kelts D., Hershberg R.M., Elson C.O., Targan S.R., Taylor K.D., Rotter J.I., Yang H., Western Regional Pediatric IBD Research Alliance. Serum immune responses predict rapid disease progression among children with Crohn’s disease: immune responses predict disease progression. Am. J. Gastroenterol. 2006; 101: 360–367. doi: 10.1111/j.1572-0241.2006.00456.x

13. Dubinsky M.C., Kugathasan S., Mei L., Picornell Y., Nebel J., Wrobel I., Quiros A., Silber G., Wahbeh G., Katzir L., Vasiliauskas E., Bahar R., Otley A., Mack D., Evans J., Rosh J., Hemker M.O., Leleiko N., Crandall W., Langton C., Landers C., Taylor K.D., Targan S.R., Rotter J.I., Markowitz J., Hyams J. Increased immune reactivity predicts aggressive complicating Crohn’s disease in children. Clinical gastroenterology and hepatology: the official clinical practice. J. Am. Gastroenterol. Assoc. 2008; 6: 1105–1111. doi: 10.1016/j.cgh.2008.04.032

14. Costa F., Mumolo M.G., Ceccarelli L., Bellini M., Romano M.R., Sterpi C., Ricchiuti A., Marchi S., Bottai M. Calprotectin is a stronger predictive marker of relapse in ulcerative colitis than in Crohn’s disease. Gut. 2005; 54: 364–368. doi: 10.1136/gut.2004.043406

15. Tibble J.A., Sigthorsson G., Bridger S., Fagerhol M.K., Bjarnason I. Surrogate markers of intestinal inflammation are predictive of relapse in patients with inflammatory bowel disease. Gastroenterology. 2000; 119: 15–22. doi: 10.1053/gast.2000.8523

16. Labaere D., Smismans A., Van Olmen A., Christiaens P., D’Haens G., Moons V., Cuyle P.-J., Frans J., Bossuyt P. Comparison of six different calprotectin assays for the assessment of inflammatory bowel disease. United Eur. Gastroenterol J. 2014; 2: 30–37. doi: 10.1177/2050640613518201

17. Calafat M., Cabre E., Manosa M., Lobatón T., Marín L., Domènech E. High within-day variability of fecal calprotectin levels in patients with active ulcerative colitis: what is the best timing for stool sampling? Inflamm. Bowel Dis. 2015; 21: 1072–1076. doi: 10.1097/MIB.0000000000000349

18. D’Inca R., Dal Pont E., di Leo V., Benazzato L., Martinato M., Lamboglia F., Oliva L., Sturniolo G.C. Can calprotectin predict relapse risk in inflammatory bowel disease? Am. J. Gastroenterol. 2008; 103: 2007–2014. doi: 10.1111/j.1572-0241.2008.01870.x

19. Sipponen T., Kolho K.L. Faecal calprotectin in children with clinically quiescent inflammatory bowel disease. Scand. J. Gastroenterol. 2010; 45: 872–877. doi: 10.3109/00365521003782389

20. Walkiewicz D., Werlin S.L., Fish D., Scanlon M., Hanaway P., Kugathasan S. Fecal calprotectin is useful in predicting disease relapse in pediatric inflammatory bowel disease. Inflamm. Bowel Dis. 2008; 14: 669–673. doi: 10.1002/ibd.20376

21. Consigny Y., Modigliani R., Colombel J.F., Dupas J.L., Lemann M., Mary J.Y., Groupe d’Etudes Thérapeutiques des Affections Inflammatoires Diges-tives (GETAID). A simple biological score for predicting low risk of short-term relapse in Crohn’s disease. Inflamm. Bowel Dis. 2006; 12: 551–557. doi: 10.1097/01.ibd.0000225334.60990.5b

22. Brignola C., Campieri M., Bazzocchi G., Farruggia P., Tragnone A., Lanfranchi G.A. A laboratory index for predicting relapse in asymptomatic patients with Crohn’s disease. Gastroenterology. 1986; 91: 1490–1494. doi: 10.1016/0016-5085(86)90206-4

23. Bitton A., Peppercorn M.A., Antonioli D.A., Niles J.L., Shah S., Bousvaros A., Ransil B., Wild G., Cohen A., Edwardes M.D., Stevens A.C. Clinical, biological, and histologic parameters as predictors of relapse in ulcerative colitis. Gastroenterology. 2001; 120 (1): 13–20. doi: 10.1053/gast.2001.20912

24. Клинические рекомендации «Язвенный колит» (утв. Минздравом России). Режим доступа: https://legalacts.ru/doc/klinicheskie-rekomendatsii-iazvennyi-kolit-utv-minzdravom-rossii/Clinicalguidelines«Ulcerativecolitis» (approved by the Minzdrav of Russia). Available at: https://legalacts.ru/doc/klinicheskie-rekomendatsii-iazvennyi-kolit-utv-minzdravom-rossii/ [In Russian].

25. Clinical practice guidelines for the diagnosis and treatment of Crohn’s disease in adults (Draft). Koloproktologiya = Coloproctology. 2020; 19 (2): 8–38. [In Russian]. doi: 10.33878/2073–7556–2020–19–2–8–38

26. Katsaros M., Paschos P., Giouleme O. Red cell distribution width as a marker of activity in inflammatory bowel disease: a narrative review. Ann. Gastroenterol. 2020; 33 (4): 348–354. doi: 10.20524/aog.2020.0486

27. Schiffman F.J. Pathophysiology of blood. Moscow – Saint-Petersburg: BINOM Publishing House–Nevsky Dialogue, 2000. 448 p. [In Russian].

28. Scoville E.A., Allaman M.M., Adams D.W., Motley A.K., Peyton S.C., Ferguson S.L., Horst S.N., Williams C.S., Beaulieu D.B., Schwartz D.A., Wilson K.T., Coburn L.A. Serum polyunsaturated fatty acids correlate with serum cytokines and clinical disease activity in Crohn’s disease. Sci. Rep. 2019; 9 (1): 2882. doi: 10.1038/s41598-019-39232-z

29. Wiese D.M., Horst S.N., Brown C.T., Allaman M.M., Hodges M.E., Slaughter J.C., Druce J.P., Beaulieu D.B., Schwartz D.A., Wilson K.T., Coburn L.A. Serum fatty acids are correlated with inflammatory cytokines in ulcerative colitis. PLoS ONE. 2016; 11 (5): e0156387. doi: 10.1371/journal.pone.0156387

30. Gatto C., Milanick M. Red blood cell Na pump: Insights from species differences. Blood Cells. Mol. Dis. 2009; 42 (3): 192–200. doi: 10.1016/j.bcmd.2009.01.011

31. Zinchuk V.V. Deformability of erythrocytes: physiological aspects. Uspekhi fiziologicheskikh nauk = Advances in Physiological Sciences. 2001; 30 (3): 66–76. [In Russian].

32. Mikhailenko E.G., Vasilenko L.V. Predicting the likelihood of developing gestosis. Akusherstvo i ginekologiya = Obstetrics and Gynecology. 1991; 6: 10–13. [In Russian].

33. Uyarel H., Ergelen M., Cicek G., Kaya M.G., Ayhan E., Turkkan C., Yıldırım E., Kırbas V., Onturk E.T., Erer H.B., Yesilcimen K., Gibson C.M. Red cell distribution width as a novel prognostic marker in patients undergoing primary angioplasty for acute myocardial infarction. Coron. Artery Dis. 2011; 22 (3): 138–144. doi: 10.1097/MCA.0b013e328342c77b

34. von Schacky C. Omega-3 Index and sudden cardiac death. Nutrients. 2010; 2 (3): 375–388. doi: 10.3390/nu2030375

35. Salisbury A.C., Amin A.P., Harris W.S., Chan P.S., Gosch K.L., Rich M.W., O’Keefe J.H.Jr, Spertus J.A. Predictors of omega-3 index in patients with acute myocardial infarction. Mayo Clinic. Proc. 2011; 86 (7): 626–632. doi: 10.4065/mcp.2011.0005

36. Harris W.S., Kennedy K.F., O’Keefe J.H.Jr, Spertus J.A. Red blood cell fatty acid levels improve GRACE score prediction of 2-yr mortality in patients with myocardial infarction. Int. J. Cardiol. 2013; 168 (1): 53–59. doi: 10.1016/j.ijcard.2012.09.076

37. Groen K., Maltby V.E., Scott R.J., Tajouri L., Lechner-Scott J. Erythrocyte microRNAs show biomarker potential and implicate multiple sclerosis susceptibility genes. Clin. Transl. Med. 2020; 10 (1): 74–90. doi: 10.1002/ctm2.22

38. Pedrazzani C., Tripepi M., Turri G., Fernandes E., Scotton G., Conci S., Campagnaro T., Ruzzenente A., Guglielmi A. Prognostic value of red cell distribution width (RDW) in colorectal cancer. Results from a single-center cohort on 591 patients. Sci. Rep. 2020; 10 (1): 1072. doi: 10.1038/s41598-020-57721-4


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For citations:


Kruchinina M.V., Svetlova I.O., Azgaldyan A.V., Gromov A.A., Generalov V.M., Yakovina I.N., Shestov A.A. Electrical and viscoelastic parameters of erythrocytes as predictors of exacerbation in inflammatory bowel diseases. Сибирский научный медицинский журнал. 2021;41(5):96-112. (In Russ.) https://doi.org/10.18699/SSMJ20210513

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