Dynamics of leukocytic blood parameters depending on the activity of inflammatory bowel disease in children

Aim: to establish the patterns of changes in leukocyte blood parameters to determine their diagnostic significance in the different activity of Crohn’s disease (CD) and ulcerative colitis (UC) in children.

Materials and methods. 370 5–18-year children (198 boys, 172 girls) with inflammatory bowel disease (IBD) were examined. Leukocytic blood parameters, concentrations of C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), faecal calprotectin (FC) levels were determined. Changes in clinical activity in Crohn’s disease (CD) and ulcerative colitis (UC) cases were determined using pediatric activity indices: PCDAI and PUCAI, respectively. Analysis of endoscopic activity in 160 CD and UC patients was determined using the scales: SES-CD and UCEIS, respectively.

Results. It was found that with an increase in the clinical activity of CD in children, the absolute numbers of leukocytes, lymphocytes and monocytes did not change significantly. In contrast, a significant increase in neutrophil reactivity was noted. In patients with high endoscopic CD activity an increase in the absolute number of monocytes and neutrophil reactivity was found. In patients with high clinical activity of UC, an increase in the number of leukocytes and the absolute number of neutrophils was found. At the same time, the granularity and reactivity of neutrophils increased from remission to moderate and high clinical activity of UC. In children with high endoscopic UC activity, the number of leukocytes, the absolute number of neutrophils and monocytes increased. At the same time, the granularity of neutrophils significantly increased as the endoscopic activity of UC increased from remission to moderate activity. Leukocyte parameters in UC patients correlated moderately with FC level, and the absolute number of neutrophils was closely related to its content. The granularity and reactivity of neutrophils positively correlated with ESR and CRP levels in children with CD and CRP concentrations in children with UC.

Conclusion. The established patterns of changes in the quantitative composition of leukocytes and their functional properties (reactivity and granularity) are directly determined by the different activity of IBD in children and have diagnostic value.

Contribution:
Semikina E.L., Tsvetkova V.S., Potapov A.S. — research concept and design;
Tsvetkova V.S., Surkov A.N., Lokhmatov M.M., Kopyltsova E.A., Akulova S.S. — collection and processing of material;
Tsvetkova V.S., Semikina E.L. — statistical processing;
Tsvetkova V.S., Semikina E.L. — text writing;
Fisenko A.P., Semikina E.L., Potapov A.S. — editing.
All co-authors — approval of the final version of the article, responsibility for the integrity of all parts of the article.

Acknowledgment. The study had no sponsorship.

Conflict of interest. The authors declare no conflict of interest.

Received: May 21, 2021
Accepted: June 23, 2021
Published: July 16, 2021

1. Holtman G.A., Leeuwen Y., Day A.S., Fagerberg U.L., Henderson P., Leach S.T., et al. Use of laboratory markers in addition to symptoms for diagnosis of inflammatory bowel disease in children: a meta-analysis of individual patient data. JAMA Pediatr. 2017; 171(10): 984-91. https://doi.org/10.1001/jamapediatrics.2017.1736

2. Dilillo D., Zuccotti G.V., Galli E., Meneghin F., Dell’Era A., Penagini F., et al. Noninvasive testing in the management of children with suspected inflammatory bowel disease. Scand. J. Gastroenterol. 2019; 54(5): 586-91. https://doi.org/10.1080/00365521.2019.1604799

3. Park C.H., Park C.J., Lee B.R., Kim M. J., Han M.Y., Cho Y.U., et al. Establishment of age- and gender-specific reference ranges for 36 routine and 57 cell population data items in a new automated blood cell analyzer, Sysmex XN-2000. Ann. Lab. Med. 2016; 36(3): 244-9. https://doi.org/10.3343/alm.2016.36.3.244

4. Aydemir Y., Pınar A., Hızal G., Demir H., Temizel S., Özen H., et al. Neutrophil volume distribution width as a new marker in detecting inflammatory bowel disease activation. Int. J. Lab. Hematol. 2017; 39(1): 51-7. https://doi.org/10.1111/ijlh.12574

5. Park S.H., Park C.J., Lee B.R., Nam K.S., Kim M.J., Han M.Y., et al. Sepsis affects most routine and cell population data (CPD) obtained using the Sysmex XN-2000 blood cell analyzer: neutrophil-related CPD NE-SFL and NE-WY provide useful information for detecting sepsis. Int. J. Lab. Hematol. 2015; 37(2): 190-8. https://doi.org/10.1111/ijlh.12261

6. Buoro S., Seghezzi M., Vavassori M., Dominoni P., Esposito S.A., Manenti B., et al. Clinical significance of cell population data (CPD) on Sysmex XN9000 in septic patients with or without liver impairment. Ann. Transl. Med. 2016; 4(21): 418. https://doi.org/10.21037/atm.2016.10.73

7. Wallace K.L., Zheng L.B., Kanazawa Y., Shih D.Q. Immunopathology of inflammatory bowel disease. World J. Gastroenterol. 2014; 20(1): 6-21. https://doi.org/10.3748/wjg.v20.i1.6

8. Vermeire S., Van Assche G., Rutgeerts P. Laboratory markers in IBD: useful, magic, or unnecessary toys? Gut. 2006; 55(3): 426-31. https://doi.org/10.1136/gut.2005.069476

9. Takaki Y., Mizuochi T., Eda K., Ishihara J., Yamashita Y. Laboratory values in Japanese children with newly diagnosed inflammatory bowel disease. Pediatr. Int. 2019; 61(7): 720-5. https://doi.org/10.1111/ped.13892

10. Xu M., Cen M., Chen X., Chen H., Liu X., Cao Q. Correlation between serological biomarkers and disease activity in patients with inflammatory bowel disease. Biomed. Res. Int. 2019; 2019: 6517549. https://doi.org/10.1155/2019/6517549

11. Zhou G.X., Liu Z.J. Potential roles of neutrophils in regulating intestinal mucosal inflammation of inflammatory bowel disease. J. Dig. Dis. 2017; 18(9): 495-503. https://doi.org/10.1111/1751-2980.12540

12. Wéra O., Lancellotti P., Oury C. The dual role of neutrophils in inflammatory bowel diseases. J. Clin. Med. 2016; 5(12): 118. https://doi.org/10.3390/jcm5120118

13. Muthas D., Reznichenko A., Balendran C.A., Böttcher G., Clausen I.G., Mårdh C.K., et al. Neutrophils in ulcerative colitis: a review of selected biomarkers and their potential therapeutic implications. Scand. J. Gastroenterol. 2017; 52(2): 125-35. https://doi.org/10.1080/00365521.2016.1235224

14. Phillipson M., Kubes P. The healing power of neutrophils. Trends Immunol. 2019; 40(7): 635-47. https://doi.org/10.1016/j.it.2019.05.001

15. Therrien A., Chapuy L., Bsat M., Rubio M., Bernard G., Arslanian E., et al. Recruitment of activated neutrophils correlates with disease severity in adult Crohn’s disease. Clin. Exp. Immunol. 2019; 195(2): 251-64. https://doi.org/10.1111/cei.13226

16. Lężyk-Ciemniaka E., Tworkiewicza M., Wilczyńskaa D., Szaflarska-Popławskab A., Krogulska A. Usefulness of testing for fecal calprotectin in pediatric gastroenterology clinical practice. Med. Princ. Pract. 2020. https://doi.org/10.1159/000512631

17. Curciarello R., Sobande T., Jones S., Giuffrida P., Sabatino A.D., Docena G.H., et al. Human neutrophil elastase proteolytic activity in ulcerative colitis favors the loss of function of therapeutic monoclonal antibodies. J. Inflamm. Res. 2020; 13: 233-43. https://doi.org/10.2147/JIR.S234710

18. Chami B., Martin N.J., Dennis J.M., Paul K., Witting P.K. Myeloperoxidase in the inflamed colon: A novel target for treating inflammatory bowel disease. Arch. Biochem. Biophys. 2018; 645: 61-71. https://doi.org/10.1016/j.abb.2018.03.012

19. Siddiqui I., Majid H., Abid S. Update on clinical and research application of fecal biomarkers for gastrointestinal diseases. World J. Gastrointest. Pharmacol. Ther. 2017; 8(1): 39-46. https://doi.org/10.4292/wjgpt.v8.i1.39

20. Zhou G., Yu L., Fang L., Yang W., Yu T., Miao Y., et al. CD177 + neutrophils as functionally activated neutrophils negatively regulate IBD. Gut. 2018; 67(6): 1052-63. https://doi.org/10.1136/gutjnl-2016-313535

21. Minar P., Jackson K., Tsai Y.T., Sucharew H., Rosen M.J., Denson L.A. Validation of neutrophil CD64 Blood biomarkers to detect mucosal inflammation in pediatric Crohn’s disease. Inflamm Bowel Dis. 2017; 24(1): 198-208. https://doi.org/10.1093/ibd/izx022

22. Park D.H., Park K., Park J., Park H.H., Chae H., Lim J., et al. Screening of sepsis using leukocyte cell population data from the Coulter automatic blood cell analyzer DxH800. Int. J. Lab. Hematol. 2011; 33(4): 391-9. https://doi.org/10.1111/j.1751-553X.2011.01298.x

23. Urrechaga E., Bóveda O., Aguirre U. Role of leucocytes cell population data in the early detection of sepsis. J. Clin. Pathol. 2018; 71(3): 259-66. https://doi.org/10.1136/jclinpath-2017-204524

24. Mayanskiy N.A., Balabanov A.S., Kopyl’tsova E.A., Lukoyanova O.L., Mel’nichuk O.S., Blinova T.A., et al. Pediatric reference intervals for leukocytes and platelets defined by an automated hematological analyzer. Voprosy diagnostiki v pediatrii. 2011; 3(6): 5–10. (in Russian)

25. Wallach J. Interpretation of Diagnostic Tests. 8th ed. Philadelphia: Lippincott Williams &Wilkins; 2007

26. Rumyantsev A.G., Samochatova E.V. A Practical Guide of Childhood Diseases. Volume 4. Hematology/Oncology in Children [Prakticheskoe rukovodstvo po detskim boleznyam. Tom 4. Gematologiya/onkologiya detskogo vozrasta]. Moscow: Medpraktika-M; 2004. (in Russian)

27. Carman N., Tomalty D., Church P.C., Mack D.R., Benchimol E.I., Otley A.R., et al. Clinical disease activity and endoscopic severity correlate poorly in children newly diagnosed with Crohn’s disease. Gastrointest. Endosc. 2019; 89(2): 364-72. https://doi.org/10.1016/j.gie.2018.09.025