Is Serum Tryptase a Dependable Biomarker for Diagnosing and Tracking Rheumatoid Arthritis?

Abstract

Aim: Our aim in this study was to demonstrate that rheumatoid arthritis (RA) patients have an increase in serum tryptase concentrations and that this correlates with the level of disease activity. Material and Method: The research involved 43 patients RA and 37 healthy participants as the control group. The average ages of the patients and the control group were 52.53±11.10 and 48.41±12.79 years, respectively. Sociodemographic information of all participants was recorded. Disease Activity Score 28 (DAS28), Health Assessment Questionnaire (HAQ) and Visual Analog Scale (VAS) scores were calculated after detailed examination to determine disease activity. Total serum tryptase concentrations were evaluated using enzyme-linked immunosorbent assay (ELISA). Results: Serum tryptase levels were higher in the RA group compared to the healthy group and a statistically significant difference was found (p<0.001). A meaningful connection was detected between serum tryptase concentrations and DAS28, VAS and HAQ scores in RA patients (p<0.05). Erythrocyte sedimentation rate (ESR) and serum tryptase levels showed a notable and significant association (p<0.05). There was no statistically significant correlation between serum tryptase concentrations and C-reactive protein (CRP) (p>0.05). Conclusion: The findings reveal that serum tryptase levels are upregulated in subjects with RA and demonstrate a correlation with disease activity. Serum tryptase may contribute to inflammation in RA.

Keywords

• Biomarker
• diagnosing
• rheumatoid arthritis
• serum tryptase

Kaynakça

1. Afifi N, B MM, Abdel Ghani AM, Mohamed Ali Hassan HGE, Behiry ME. Value of albumin-fibrinogen ratio and CRP-albumin ratio as predictor marker of disease activity in Egyptian RA patients, correlated with musculoskeletal sonography. Open Access Rheumatol. 2020;12:241-8.
2. Chen S, Ying H, Du J, et al. The association between albumin-dNLR score and disease activity in patients with rheumatoid arthritis. J Clin Lab Anal. 2019;33:e22695.
3. McInnes IB, Schett G. The pathogenesis of rheumatoid arthritis. N Engl J Med. 2011;365:2205-19.
4. Metcalfe DD, Baram D, Mekori YA. Mast cells. Physiol Rev. 1997;77:1033-79.
5. Sprinzl B, Greiner G, Uyanik G, et al. Genetic regulation of tryptase production and clinical impact: hereditary alpha tryptasemia, mastocytosis and beyond. Int J Mol Sci. 2021;22:2458.
6. Theoharides TC, Valent P, Akin C. Mast cells, mastocytosis, and related disorders. N Engl J Med. 2015;373:163-72.
7. Guo Y, Wu Q, Ni B, et al. Tryptase is a candidate autoantigen in rheumatoid arthritis. Immunology. 2014;142:67-77.
8. Bargagli E, Mazzi A, Mezzasalma F, et al. The analysis of tryptase in serum of sarcoidosis patients. Inflammation. 2009;32:310-4.

9. Liu B, Yang MQ, Yu TY, et al. Mast cell tryptase promotes inflammatory bowel disease-induced intestinal fibrosis. Inflamm Bowel Dis. 2021;27:242-55.
10. Zhang MQ, Timmerman H. Mast cell tryptase and asthma. Mediators Inflamm. 1997;6:311-7.
11. Numerof RP, Simpson PJ, Tanaka R. Tryptase inhibitors: a novel class of anti-inflammatory drugs. Expert Opin Investig Drugs. 1997;6:811-7.
12. Compton SJ, Cairns JA, Holgate ST, Walls AF. The role of mast cell tryptase in regulating endothelial cell proliferation, cytokine release, and adhesion molecule expression: tryptase induces expression of mRNA for IL-1 beta and IL-8 and stimulates the selective release of IL-8 from human umbilical vein endothelial cells. J Immunol. 1998;161:1939-46.
13. Zhang S, Zeng X, Yang H, et al. Mast cell tryptase induces microglia activation via protease-activated receptor 2 signaling. Cell Physiol Biochem. 2012;29:931-40.
14. Zeng X, Zhang S, Xu L, et al. Activation of protease-activated receptor 2-mediated signaling by mast cell tryptase modulates cytokine production in primary cultured astrocytes. Mediators Inflamm. 2013;2013:140812.
15. Pejler G, Alanazi S, Grujic M, et al. Mast cell tryptase potentiates neutrophil extracellular trap formation. J Innate Immun. 2022;14:433-46.
16. Meyer MC, Creer MH, McHowat J. Potential role for mast cell tryptase in recruitment of inflammatory cells to endothelium. Am J Physiol Cell Physiol. 2005;289:C1485-91.
17. Mohajeri M, Kovanen PT, Bianconi V, et al. Mast cell tryptase - Marker and maker of cardiovascular diseases. Pharmacol Ther. 2019;199:91-110.
18. Prevoo ML, van 't Hof MA, Kuper HH, et al. Modified disease activity scores that include twenty-eight-joint counts. Development and validation in a prospective longitudinal study of patients with rheumatoid arthritis. Arthritis Rheum. 1995;38:44-8.
19. Price DD, McGrath PA, Rafii A, Buckingham B. The validation of visual analogue scales as ratio scale measures for chronic and experimental pain. Pain. 1983;17:45-56.
20. Küçükdeveci AA, Sahin H, Ataman S, et al. Issues in cross-cultural validity: example from the adaptation, reliability, and validity testing of a Turkish version of the Stanford Health Assessment Questionnaire. Arthritis Rheum. 2004;51:14-9.
21. Traina G. Mast cells in human health and diseases 2.0. Int J Mol Sci. 2024;25:6443.
22. Nassar A, Wagura E, Loukas M. Mast cells and arteriogenesis: a systematic review. Cardiovasc Pathol. 2025;75:107716.
23. Oštrić Pavlović I, Radović S, Krtinić D, et al. Tryptase: the silent witness of past and ongoing systemic events. Medicina (Kaunas, Lithuania). 2024;60:1380.
24. Min HK, Kim KW, Lee SH, Kim HR. Roles of mast cells in rheumatoid arthritis. Korean J Intern Med. 2020;35:12-24.
25. Rivellese F, Mauro D, Nerviani A, et al. Mast cells in early rheumatoid arthritis associate with disease severity and support B cell autoantibody production. Ann Rheum Dis. 2018;77:1773-81.
26. Kim KW, Kim BM, Won JY, et al. Regulation of osteoclastogenesis by mast cell in rheumatoid arthritis. Arthritis Res Ther. 2021;23:124.
27. Rivellese F, Rossi FW, Galdiero MR, et al. Mast cells in early rheumatoid arthritis. Int J Mol Sci. 2019;20:2040.
28. Rossini M, Viapiana O, Zanoni G, et al. Serum levels of tryptase suggest that mast cells might have an antiinflammatory role in rheumatoid arthritis: comment on the article by Rivellese et al. Arthritis Rheumatol. 2016;68:769.
29. Zhou HH, Tang YL, Xu TH, Cheng B. C-reactive protein: structure, function, regulation, and role in clinical diseases. Front Immunol. 2024;15:1425168.
30. Bray C, Bell LN, Liang H, et al. Erythrocyte sedimentation rate and C-reactive protein measurements and their relevance in clinical medicine. WMJ. 2016;115:317-21.
31. Paolino G, Di Nicola MR, Currado M, et al. Serum tryptase levels in patients with psoriasis: a pilot study for a possible useful biomarker. Clin Exp Dermatol. 2022;47:178-9.
32. Chimenti MS, Sunzini F, Fiorucci L, et al. Potential role of cytochrome c and tryptase in psoriasis and psoriatic arthritis pathogenesis: focus on resistance to apoptosis and oxidative stress. Front Immunol. 2018;9:2363.