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Egyptian Rheumatology and Rehabilitation
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Relation of interleukin-15 with the severity of primary knee osteoarthritis

Egyptian Rheumatology and Rehabilitation volume 46, pages 313–320 (2019)Cite this article

Abstract

Background

Interleukin-15 (IL-15) is a proinflammatory cytokine. IL-15 could be considered a potential biomarker for primary knee osteoarthritis (OA).

Aim

This study aimed to assess the serum level of IL-15 in primary knee OA patients and assess its relation to clinical severity, functional disabilities, and radiological grading of knee OA.

Patients and methods

This study included 40 patients with primary knee OA and 40 apparently healthy individuals. Assessment of knee OA was performed using clinical examination, the Western Ontario and McMaster Universities Osteoarthritis Index score, and Health Assessment Questionnaire-Disability Index. Radiological assessment was performed using the Kellgren–Laurence grading scale. Serum level of IL-15 was measured in both patients and control participants.

Results

There were no statistically significant differences between patients and the control group in sex (P=1.000) and age (P=0.247). The patient group had a statistically significantly higher serum IL-15 level than its level in the control group (P≤0.0001). Serum IL-15 level was significantly higher among patients with knee joint line tenderness and effusion (P≤0.0001). There were statistically significant positive correlations between serum IL-15 level with the Western Ontario and McMaster Universities Osteoarthritis Index total score (P≤0.0001), the Health Assessment Questionnaire-Disability Index score (P≤0.0001), and the Kellgren–Laurence grading scale (P≤0.0001).

Conclusion

Serum IL-15 is elevated and correlated positively with pain, stiffness, functional disabilities, as well as radiological damage in primary knee OA. This suggests that IL-15 plays an important critical role in the pathogenesis of primary knee OA-related pain, stiffness, and joint damage. IL-15 might be a potential biomarker for assessing the severity of primary knee OA.

References

  1. Abhishek A, Doherty M. Diagnosis and clinical presentation of osteoarthritis. Rheum Dis Clin North Am 2013; 39:45–66.

    Article  CAS  Google Scholar 

  2. Lawrence R, Felson D, Helmick C. Estimates of the prevalence of arthritis and other rheumatic conditions in the United States. Part II. Arthritis Rheum 2008; 58:26–35.

    Article  Google Scholar 

  3. Hunter DJ, Johnson VL. The epidemiology of osteoarthritis. Best Pract Res Clin Rheumatol 2014; 28:5–15.

    Article  Google Scholar 

  4. Palazzo C, Nguyen C, Lefevre-Colau M, Rannou F, Poiraudeau S. Risk factors and burden of osteoarthritis. Ann Phys Rehabil Med 2016; 59:134–138.

    Article  Google Scholar 

  5. Felson D. An update on the pathogenesis and epidemiology of osteoarthritis. Radiol Clin North Am 2004; 42:1–9.

    Article  Google Scholar 

  6. Kapoor M, Martel-Pelletier J, Lajeunesse D, Pelletier J, Fahmi H. Role of proinflammatory cytokines in the pathophysiology of osteoarthritis. Nat Rev Rheumatol 2011; 7:33–42.

    Article  CAS  Google Scholar 

  7. Wojdasiewicz P, Poniatowski LA, Szukiewicz D. The role of inflammatory and anti-inflammatory cytokines in the pathogenesis of osteoarthritis. Mediators Inflamm 2014; 2014:561459.

    Article  Google Scholar 

  8. Han MY, Dai JJ, Zhang Y, Lin Q, Jiang M, Xu XY, et al. Identification of osteoarthritis biomarkers by proteomic analysis of synovial fluid. J Int Med Res 2012; 40:2243–2250.

    Article  CAS  Google Scholar 

  9. Dubois S, Mariner J, Waldmann TA, Tagaya Y. IL-15Rα recycles and presents IL-15 in trans to neighboring cells. Immunity 2002; 17:537–547.

    Article  CAS  Google Scholar 

  10. Sun JM, Sun LZ, Liu J, Su BH, Shi L. Serum interleukin-15 levels are associated with severity of pain in patients with knee osteoarthritis. Dis Markers 2013; 35:203–206.

    Article  Google Scholar 

  11. Scanzello CR, Umoh E, Pessler F, Diaz-Torne C, Miles T, DiCarlo E, et al. Local cytokine profiles in knee osteoarthritis: elevated synovial fluid interleukin-15 differentiates early from end-stage disease. Osteoarthritis Cartilage 2009; 17:1040–1048.

    Article  CAS  Google Scholar 

  12. Altman R, Asch E, Bloch D. Development of criteria for the classification and reporting of osteoarthritis. Classification of osteoarthritis of the knee. Diagnostic and therapeutic criteria committee of the American Rheumatism Association. Arthritis Rheum 1986; 29:1039–1049.

    CAS  PubMed  Google Scholar 

  13. McConnell S, Kolopack P, Davis AM. The Western Ontario and McMaster Universities Arthritis Index (WOMAC): a review of its utility and measurement properties. Arthritis Rheum 2001; 45:453–461.

    Article  CAS  Google Scholar 

  14. Bruce B, Fries J. The Health Assessment Questionnaire (HAQ). Clin Exp Rheumatol 2005; 23:14–18.

    Google Scholar 

  15. Emrani P, Katz J, Kessler C, Reichmann W, Wright E, McAlindon T, et al. Joint space narrowing and Kellgren-Lawrence progression in knee osteoarthritis: an analytic literature synthesis. Osteoarthritis Cartilage 2008; 16:873–882.

    Article  CAS  Google Scholar 

  16. SPSS. Statistical package for the social sciences, version 17. London: University of Cambridge Computing Service; 2007.

    Google Scholar 

  17. Appuhamy S, Munidasa SMPD. Study of epidemiology, symptom variability and knowledge assessment of knee joint osteoarthritis patients in Sri Lanka [abstract]. Int J Rheum Dis 2019; 22:48.

    Google Scholar 

  18. Mora JC, Przkora R, Cruz-Almeida Y. Knee osteoarthritis: pathophysiology and current treatment modalities. J Pain Res 2018; 11:2189–2196.

    Article  CAS  Google Scholar 

  19. Berenbaum F. Osteoarthritis as an inflammatory disease (osteoarthritis is not osteoarthrosis!). Osteoarthritis Cartilage 2013; 21:16–21.

    Article  CAS  Google Scholar 

  20. Mabey T, Honsawek S. Cytokines as biochemical markers for knee osteoarthritis. World J Orthop 2015; 6:95–105.

    Article  Google Scholar 

  21. Nguyen LT, Sharma AR, Chakraborty C, Saibaba B, Ahn ME, Lee SS. Review of prospects of biological fluid biomarkers in osteoarthritis. Int J Mol Sci 2017; 18:601.

    Article  Google Scholar 

  22. Abdel Ghany HM, El Tawab SS, Moghazy AM. Urinary C-terminal telopeptide of type II collagen, radiological severity, and functional assessment in knee osteoarthritis: are these related? Egypt Rheumatol Rehabil 2016; 43:73–77.

    Article  Google Scholar 

  23. Gaballah A, Hussein N, Risk M,Elsawy N, Elabasiry S. Correlation between synovial vascular endothelial growth factor, clinical, functional and radiological manifestations in knee osteoarthritis. Egypt Rheumatol 2016; 38:29–34.

    Article  Google Scholar 

  24. Ibrahim IK, Shahine EM, El-Hadedy AS, Saba EKA, Hussein GSA. Role of interleukin-18 in primary knee osteoarthritis: clinical, laboratory and radiological study [abstract]. Int J Med Health Sci 2016; 3:123.

    Google Scholar 

  25. Mohamed SA, Neseem NO, Metwally SS, Farag SEDM. IL-17 in primary knee osteoarthritis and its relation with severity of the disease. Int J Clin Rheumatol 2018; 13:364–369.

    Article  Google Scholar 

  26. Ling SM, Patel DD, Garnero P, Zhan M, Vaduganathan M, Muller D, et al. Serum protein signatures detect early radiographic osteoarthritis. Osteoarthritis Cartilage 2009; 17:43–48.

    Article  CAS  Google Scholar 

  27. Carroll HP, Paunovic V, Gadina M. Signaling, inflammation and arthritis: crossed signals: the role of interleukin-15 and -18 in autoimmunity. Rheumatology 2008; 47:1269–1277.

    Article  CAS  Google Scholar 

  28. Hill CL, Hunter DJ, Niu J, Clancy M, Guermazi A, Genant H, et al. Synovitis detected on magnetic resonance imaging and its relation to pain and cartilage loss in knee osteoarthritis. Ann Rheum Dis 2007; 66:1599–1603.

    Article  Google Scholar 

  29. Ayral X, Pickering EH, Woodworth TG, Mackillop N, Dougados M. Synovitis: a potential predictive factor of structural progression of medial tibiofemoral knee osteoarthritis - results of a 1-year longitudinal arthroscopic study in 422 patients. Osteoarthritis Cartilage 2005; 13:361–367.

    Article  CAS  Google Scholar 

  30. Mcinnes IB, Al-Mughales J, Field M, Leung BP, Huang FP, Dixon R, et al. The role of interleukin-15 in T-cell migration and activation in rheumatoid arthritis. Nat Med 1996; 2:175–182.

    Article  CAS  Google Scholar 

  31. Mathiessen A, Conaghan PG. Synovitis in osteoarthritis: current understanding with therapeutic implications. Arthritis Res Ther 2017; 19:18.

    Article  Google Scholar 

  32. Waldmann TA, Dubois S, Tagaya Y. Contrasting roles of IL-2 and IL-15 in the life and death of lymphocytes: implications for immunotherapy. Immunity 2001; 14:105–110.

    CAS  PubMed  Google Scholar 

  33. Perera PY, Lichy JH, Waldmann TA, Perera LP. The role of interleukin-15 in inflammation and immune responses to infection: implications for its therapeutic use. Microbes Infect 2012; 14:247–261.

    Article  CAS  Google Scholar 

  34. Kobayashi H, Dubois S, Sato N, Sabzevari H, Sakai Y, Waldmann TA, et al. Role of trans-cellular IL-15 presentation in the activation of NK cell-mediated killing, which leads to enhanced tumor immunosurveillance. Blood 2005; 105:721–727.

    Article  CAS  Google Scholar 

  35. Klebanoff CA, Finkelstein SE, Surman DR, Lichtman MK, Gattinoni L, Theoret MR, et al. IL-15 enhances the in vivo antitumor activity of tumor-reactive CD8+T cells. Proc Natl Acad Sci USA 2004; 101:1969–1974.

    Article  CAS  Google Scholar 

  36. Judge AD, Zhang X, Fujii H, Surh CD, Sprent J. Interleukin-15 controls both proliferation and survival of a subset of memory-phenotype CD8(+) T cells. J Exp Med 2002; 196:935–946.

    Article  CAS  Google Scholar 

  37. Orita S, Koshi T, Mitsuka T, Miyagi M, Inoue G, Arai G, et al. Associations between proinflammatory cytokines in the synovial fluid and radiographic grading and pain-related scores in 47 consecutive patients with osteoarthritis of the knee. BMC Musculoskelet Disord 2011; 12:144.

    Article  CAS  Google Scholar 

  38. Constantinescu CS, Grygar C, Kappos L, Leppert D. Interleukin-15 stimulates production of matrix metalloproteinase-9 and tissue inhibitor of metalloproteinase-1 by human peripheral blood mononuclear cells. Cytokine 2001; 13:244–247.

    Article  CAS  Google Scholar 

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Authors and Affiliations

  1. Physical Medicine, Rheumatology and Rehabilitation Department, Faculty of Medicine, Alexandria University, Alexandria, 21131, Egypt

    Ibrahim K. Ibrahim & Emmanuel K. Aziz Saba MD

  2. Department of Clinical and Chemical Pathology, Faculty of Medicine, Alexandria University, Alexandria, Egypt

    Neveen L. Mikhael Saad

  3. Department of Physical Medicine, Rheumatology and Rehabilitation Department, Ministry of Health Hospitals, Ministry of Health, Alexandria, Egypt

    Doaa Y. A. Mohammed

Authors
  1. Ibrahim K. Ibrahim
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  2. Emmanuel K. Aziz Saba MD
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  3. Neveen L. Mikhael Saad
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  4. Doaa Y. A. Mohammed
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Corresponding author

Correspondence to Emmanuel K. Aziz Saba MD.

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Ibrahim, I.K., Saba, E.K.A., Saad, N.L.M. et al. Relation of interleukin-15 with the severity of primary knee osteoarthritis. Egypt Rheumatol Rehabil 46, 313–320 (2019). https://doi.org/10.4103/err.err_42_19

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  • DOI: https://doi.org/10.4103/err.err_42_19

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