Serum chitotriosidase activity in South African patients with sarcoidosis and tuberculosis

Main Article Content

R Morar
I Sinclair
C Feldman

Abstract





Background. Chitotriosidase is a chitinase enzyme that is expressed selectively through activated macrophages in humans. Increased activity of chitotriosidase in both bronchoalveolar lavage samples and serum of patients with sarcoidosis has been reported. It has been proposed that chitotriosidase could be used as a potential biomarker for diagnosis, monitoring and prognosis in sarcoidosis patients. However, no studies in a South African (SA) cohort have evaluated this potential role.


Objectives. To analyse serum chitotriosidase activity in treated and untreated sarcoidosis patients, healthy controls and patients with tuberculosis (TB). Sarcoidosis and TB are two diseases of differing aetiology that may be clinically difficult to distinguish between in the SA setting, which is a high-burden area for TB. We hoped to determine whether chitotriosidase activity levels could help differentiate the one disease from the other.


Methods. Serum chitotriosidase activity was measured in an SA cohort of treated and untreated sarcoidosis patients and compared with controls. In addition, activity in sarcoidosis patients was compared with that in TB patients. Overall, chitotriosidase activity was assayed in the serum of 12 biopsy-proven sarcoidosis patients before treatment, 9 sarcoidosis patients after at least a month’s treatment, 10 patients with confirmed pulmonary and/or disseminated TB before treatment, and 12 healthy controls. Plasma chitotriosidase activity was assayed as previously described using 4-methylumbelliferyl-β-D-N,Nʹ,N′′-triacetylchitotriose as a substrate.


Results. Significantly higher serum chitotriosidase activity was observed in sarcoidosis patients, both untreated and treated, compared with controls (p<0.05). Sarcoidosis patients had higher chitotriosidase levels than TB patients, but this difference was not significant. While chitotriosidase activity was lower in patients with TB than in those with sarcoidosis, levels were elevated compared with controls.


Conclusion. Chitotriosidase activity in patients with sarcoidosis was greater than in those with TB, and also greater compared with controls. The increased chitotriosidase activity in sarcoidosis suggests that this enzyme may be involved in the disease pathogenesis. Further investigation is required to validate these findings.





Downloads

Download data is not yet available.

Article Details

How to Cite
1.
Morar R, Sinclair I, Feldman C. Serum chitotriosidase activity in South African patients with sarcoidosis and tuberculosis. Afr J Thoracic Crit Care Med [Internet]. 2024 Dec. 11 [cited 2025 Feb. 19];30(4):e1832. Available from: https://samajournals.co.za/index.php/ajtccm/article/view/1832
Section
Original Research: Articles

How to Cite

1.
Morar R, Sinclair I, Feldman C. Serum chitotriosidase activity in South African patients with sarcoidosis and tuberculosis. Afr J Thoracic Crit Care Med [Internet]. 2024 Dec. 11 [cited 2025 Feb. 19];30(4):e1832. Available from: https://samajournals.co.za/index.php/ajtccm/article/view/1832

References

1. Chang D, Sharma L, Cruz CSD. Chitotriosidase: A marker and modulator of lung disease. Eur Respir Rev 2020;29(156):190143. https://doi.org/10.1183/16000617.0143- 2019

2. BargagliE,MargollicciM,PerroneA,etal.Chitotriosidaseanalysisinbronchoalveolar lavage of patients with sarcoidosis. Sarcoidosis Vasc Diffuse Lung Dis 2007;24(1):59- 64. https://doi.org/10.1007/s11083-007-9059-z

3. Bargagli E, Bennett D, Maggiorelli C, et al. Human chitotriosidase: A sensitive biomarker of sarcoidosis. J Clin Immunol 2013;33(1):264-270. https://doi. org/10.1007/s10875-012-9754-4

4. Harlander M, Salobir B, Zupančič M, Terčelj M. Bronchoalveolar lavage chitotriosidase activity as a biomarker of sarcoidosis. Sarcoidosis Vasc Diffuse Lung Dis 2015;32(4):313-317.

5. Dymek B, Sklepkiewicz P, Mlacki M, et al. Pharmacological inhibition of chitotriosidase (CHIT1) as a novel therapeutic approach for sarcoidosis. J Inflamm Res 2022;15:5621-5634. https://doi.org/ 10.2147/JIR.S378357

6. Crouser ED, Maier LA, Wilson KC, et al. Diagnosis and detection of sarcoidosis: An official American Thoracic Society clinical practice guideline. Am J Respir Crit Care Med 2020;201(8):e26-e51. https://doi.org/10.1164/rccm.202002-0251ST

7. HollakC,vanWeelyS,vanOersM,AertsJ.Markedelevationofplasmachitotriosidase activity: A novel hallmark of Gaucher disease. J Clin Invest 1994;93(3):1288-1292. https://doi.org/10.1172/JCI117084

8. Wajner A, Michelin K, Burin MG, et al. Biochemical characterization of chitotriosidase enzyme: Comparison between normal individuals and patients with Gaucher and with Niemann-Pick diseases. Clin Biochem 2004;37(10):893-897. https://doi.org/10.1016/j. clinbiochem.2004.06.008

9. Grosso S, Margollicci M, Bargagli E, et al. Serum levels of chitotriosidase as a marker of disease activity and clinical stage in sarcoidosis. Scand J Clin Lab Invest 2004;64(1):57-62. https://doi/ 10.1080/00365510410004092

10. Bargagli E, Margollicci M, Nikiforakis N, et al. Chitotriosidase activity in the serum of patients with sarcoidosis and pulmonary tuberculosis. Respiration 2007;74(5):548- 552. https://doi.org/10.1159/000100555

11. Terčelj M, Salobir B, Simcic S, Wraber B, Zupancic M, Rylander R. Chitotriosidase activity in sarcoidosis and some other pulmonary diseases. Scand J Clin Lab Invest 2009;69(5):575-578. https://doi.org/10.1080/00365510902829362

12. Bennett D, Cameli P, Lanzarone N, et al. Chitotriosidase: A biomarker of activity and severity in patients with sarcoidosis. Respir Res 2020;21(1):6. https://doi.org/10.1186/ s12931-019-1263-z

13. Harlander M, Salobir B, Zupančič M, Dolenšek M, Vodovnik TB, Terčelj M. Serial chitotriosidase measurements in sarcoidosis – two to five year follow-up study. Respir Med 2014;108(5):775-782. https://doi.org/10.1016/j.rmed.2014.02.002

14. Popević S, Šumarac Z, Jovanović D, et al. Verifying sarcoidosis activity: Chitotriosidase versus ACE in sarcoidosis – a case-control study. J Med Biochem 2016;35(4):390-400. https://doi.org/10.1515/jomb-2016-0017

15. Bergantini L, Bianchi F, Cameli P, et al. Prognostic biomarkers of sarcoidosis: A comparative study of serum chitotriosidase, ACE, lysozyme, and KL-6. Dis Markers 2019;2019:8565423. https://doi.org/10.1155/2019/8565423

16. Boot RG, Renkema GH, Verhoek M, et al. The human chitotriosidase gene: Nature of inherited enzyme deficiency. J Biol Chem 1998;273(40):25680-25685. https://doi. org/10.1074/jbc.273.40.25680

17. Harlander M, Maver A, Terčelj M, Salobir B, Peterlin B. Common chitotriosidase duplication gene polymorphism and clinical outcome status in sarcoidosis. Sarcoidosis Vasc Diffuse Lung Dis 2015;32(3):194-199.

18. Arndt S, Hobbs A, Sinclaire I, Lane AB. Chitotriosidase deficiency: A mutation update in an African population. JIMD Rep 2012;10:11-16. https://doi. org/10.1007/8904_2012_193

19. Artieda M, Cenarro A, Gañán A, et al. Serum chitotriosidase activity is increased in subjects with atherosclerosis disease. Arterioscler Thromb Vasc Biol 2003;23(9):1645- 1652. https://doi.org/10.1161/01.ATV.0000089329.09061.07

20. Broos CE, van Nimwegen M, Hoogsteden HC, Hendriks RW, Kool M, van den Blink B. Granuloma formation in pulmonary sarcoidosis. Front Immunol 2013;4:437. https:// doi.org/10.3389/fimmu.2013.00437

21. Patterson KC, Queval CJ, Gutierrez MG. Granulomatous inflammation in tuberculosis and sarcoidosis: Does the lymphatic system contribute to disease? Bioessays 2019;41(11):1900086. https://doi.org/10.1002/bies.201900086

22. Bargagli E, Maggiorelli C, Rottoli P. Human chitotriosidase: A potential new marker of sarcoidosis severity. Respiration 2008;76(2):234-238. https://doi.org/10.1159/000134009 23. Grunewald J, Grutters JC, Arkema EV, Saketkoo LA, Moller DR, Müller-Quernheim J. Sarcoidosis. Nat Rev Dis Primers 2019;5(1):45. https://doi.org/10.1038/s41572-019-

0096-x

24. Muthuswamy P, Lopez-Majano V, Ranginwala M, Trainor W. Serum angiotensin- converting enzyme (SACE) activity as an indicator of total body granuloma load and prognosis in sarcoidosis. Sarcoidosis 1987;4(2):142-148.

25. Schürmann M. Angiotensin-converting enzyme gene polymorphisms in patients with pulmonary sarcoidosis: Impact on disease severity. Am J Pharmacogenomics 2003;3(4):233-243. https://doi.org/10.2165/00129785-200303040-00002

26. Malaguarnera L, Musumeci M, di Rosa M, Scuto A, Musumeci S. Interferon‐gamma, tumor necrosis factor‐alpha, and lipopolysaccharide promote chitotriosidase gene expression in human macrophages. J Clin Lab Anal 2005;19(3):128-132. https://doi. org/10.1002/jcla.20063

27. Elias JA, Homer RJ, Hamid Q, Lee CG. Chitinases and chitinase-like proteins in TH2 inflammation and asthma. J Allergy Clin Immunol 2005;116(3):497-500. https://doi. org/10.1016/j.jaci.2005.06.028

28. Prasse A, Pechkovsky DV, Toews GB, et al. A vicious circle of alveolar macrophages and fibroblasts perpetuates pulmonary fibrosis via CCL18. Am J Respir Crit Care Med 2006;173(7):781-792. https://doi.org/10.1164/rccm.200509-1518OC

29. De Martino M, Lodi L, Galli L, Chiappini E. Immune response to Mycobacterium tuberculosis: A narrative review. Front Pediatr 2019;7:350. https://doi.org/10.3389/ fped.2019.00350

30. Domingo‐Gonzalez R, Prince O, Cooper A, Khader SA. Cytokines and chemokines in Mycobacterium tuberculosis infection. Microbiol Spectr 2016;4(5):10.1128/microbiolspec. TBTB2-0018-2016. https://doi.org/10.1128/microbiolspec.TBTB2-0018-2016

Similar Articles

You may also start an advanced similarity search for this article.