Interleukin 36α Serum Level in Egyptian Patients with Systemic Lupus Erythematosus and its relation to Disease Activity

Document Type : Original Article

Authors

1 Rheumatology, Faculty of Medicine, Beni-Suef University, Egypt

2 Rheumatology and Rehabilitation faculty of medicine Beni-Suef university Beni-Suef Egypt

3 Clinical Pathology Department, faculty of medicine Beni-Suef university Beni-Suef Egypt

Abstract

Background:  Systemic lupus erythematosus (SLE) is a systemic illness marked by clinical variability, unpredictable outcome, and recurring flares. Interleukin 36α is crucial for innate immunity. It is strongly hypothesized that IL-36 has an impact on SLE pathogenesis. Aim: Assessing the link between interleukin 36α levels and disease activity in systemic lupus erythematosus (SLE). Subjects and Methods: This study examined forty systemic lupus erythematosus patients and 40 controls. The SLE disease activity index (SLEDAI) establishes disease activity. ELISA estimates serum Interleukin 36α.  Results: Interleukin 36 α levels were considerably higher in SLE patients compared with the controls (P < 0.001). IL-36α levels significantly linked to the SLE disease activity index (SLEDAI) score (P <0.001), age (P = 0.002), disease duration (P = 0.00), arthritis (P <0.001), nephritis (P = 0.002), and anti-double-stranded DNA antibody (P <0.001). IL-36 α levels and complement 3 were inversely linked (P < 0.001).  Conclusion: Interleukin 36α may identify SLE activity early in follow-up.

Keywords

Main Subjects

References

  1. Fanouriakis A, Kostopoulou M, Alunno A, Aringer M, Bajema I, Boletis JN, et al. Update of the EULAR recommendations for the management of systemic lupus erythematosus. Ann Rheum Dis2019; 78(6):736–45.
  2. Somers EC, Marder W, Cagnoli P, Lewis EE, DeGuire P, Gordon C, et al. Population-based incidence and prevalence of systemic lupus erythematosus: the Michigan Lupus Epidemiology and Surveillance program. Arthritis Rheumatol 2014; 66(2): 369–78.
  3. Tsokos GC, Lo MS, Costa Reis P, Sullivan KE. New insights into the immunopathogenesis of systemic lupus erythematosus. Nat Rev Rheumatol 2016; 2(12): 716–30.
  4. Griffiths B, Mosca M, Gordon C. Assessment of patients with systemic lupus erythematosus and the use of lupus disease activity indices. Best Pract Res Clin Rheumatol 2005; 19: 685–708.
  5. van de Veerdonk FL, Netea MG. New insights in the immunobiology of IL-1 family members. Front Immunol 2013; 4(167).
  6. Tortola L, Rosenwald E, Abel B, Blumberg H, Schäfer M, Coyle AJ. Psoriasiform dermatitis is driven by IL-36-mediated DC-keratinocyte crosstalk. J Clin  Investig 2012; 122: 3965–76.
  7. Ciccia F, Accardo-Palumbo A, Alessandro R, Alessandri C, Priori R, Guggino G, et al. Interleukin-36α axis is modulated in patients with primary Sjögren's syndrome. Clin Exp Immunol 2015; 181: 230–38.
  8. Chu M, Wong CK, Cai Z, Dong J, Jiao D, Kam NW, et al. Elevated Expression and Pro-Inflammatory Activity of IL-36 in Patients with Systemic Lupus Erythematosus. Molecules 2015; 20(10): 19588-604.
  9. Mai S-Z, Li C-j, Xie X-y, Xiong H, Xu M, Zeng Q-F, et al. Increased serum IL-36α and IL-36γ levels in patients with systemic lupus erythematosus: Association with disease activity and arthritis. Int Immunopharmacol 2018; 58:103-08.
  10. Aringer M, Costenbader K, Daikh D, Brinks R, Mosca M, Goldman R, et al. European League Against Rheumatism/American College of Rheumatology classification criteria for systemic lupus erythematosus. Ann Rheum Dis 2019; 78:1151–59.
  11. Gladman DD, Ibañez D, Urowitz MB. Systemic lupus erythematosus disease activity index 2000. J Rheumatol 2002; 29(2): 288-91.
  12. Levey AS, Coresh J, Greene T, Stevens LA, Zhang YL, Hendriksen S, et al. Using Standardized Serum Creatinine Values in the Modification of Diet in Renal Disease Study Equation for Estimating Glomerular Filtration Rate. Ann Intern Med 2006; 145 (4): 247-54.
  13. Gladman D, Ginzler E, Goldsmith C, Fortin P, Liang M, Urowitz M, et al. The development and initial validation of the systemic lupus international collaborating clinics/American College of Rheumatology damage index for systemic lupus erythematosus. Arthritis Rheum1996; 39: 363–369.
  14. Weening JJ, D'agati VD, Schwartz MM, Seshan SV, Alpers CE, Appel GB, et al. The classification of glomerulonephritis in systemic lupus erythematosus revisited. Kidney Int 2004; 65(2): 521-530.‏
  15. Saha SS, Singh D, Raymond EL, Ganesan R, Caviness G, Grimaldi C, et al.  Signal transduction and intracellular trafficking by the interleukin 36 receptor. J Biol Chem 2015; 290(39): 23997–24006.
  16. Bacalao M, Satterthwaite, Alin B. Recent advances in lupus B cell biology: PI3K, IFNγ, and chromatin. Front Immunol 2021; 11: 615673.
  17. Tsai HL, Chang JW, Lu JH, Liu CS. Epidemiology and risk factors associated with avascular necrosis in patients with autoimmune diseases: a nationwide study. Korean J Intern Med 2022; 37(4): 864-76.
  18. Dunn E, Sims JE, Nicklin MJ, O'Neill LA. Annotating genes with potential roles in the immune system: six new members of the IL-1 family. Trends Immunol2001; 22: 533-36.‏
  19. Ngo VL, Abo H, Kuczma M, Szurek E, Moore N, Nusrat A, et al. IL-36R signaling integrates innate and adaptive immune-mediated protection against enteropathogenic bacteria. Proc Natl Acad Sci U S A 2020; 117(44): 27540-48.
  20. Elias M, Zhao S, Wang J, Neurath MF, Neufert C, Fiocchi C, et al. IL-36 in chronic inflammation and fibrosis—bridging the gap?. J Clin Invest 2021; 131(2).‏
  21. Carrier Y, Ma HL, Ramon HE, Napierata L, Small C, O'Toole M, et al. Inter-regulation of Th17 cytokines and the IL-36 cytokines in vitro and in vivo: implications in psoriasis pathogenesis. J Invest Dermatol 2011; 131: 2428–37.
  22. Wang YF, Zhang Y, Lin Z, Zhang H, Wang TY, Cao Y, et al. Identification of 38 novel loci for systemic lupus erythematosus and genetic heterogeneity between ancestral groups. Nat Commun 2021; 12(1): 1-13.
  23. Wong CK, Cai Z, Dong J, Jiao D, Kam NW, Chu M, et al. Elevated Expression and Pro-inflammatory Activity of IL-36 in Patients with Systemic Lupus Erythematosus. Molecules 2015; 20(10):19588–604.
  24. Elsiss NA, Senna MK, El Arman MM, Hafez EA. Clinical significance of interleukin-36 alpha and gamma in systemic lupus erythematosus patients. Egyptian Rheumatologist 2023; 45(1): 33-37.
  25. Zhang M, Xu WD, Zhu Y, Wen PF, Leng RX, Pan HF, et al. Serum levels of cytokines in systemic lupus erythematosus. Z Rheumatol 2O14; 73(3): 277–80.
  26. Mai SZ, Li CJ, Xie XY, Xiong H, Zeng F, Han YF, et al. Increased serum IL-36α and IL-36γ levels in patients with systemic lupus erythematosus: association with disease activity and arthritis. Int Immunopharmacol 2018; 58: 103-108.
  27. Mohamed AE, Zaki HM, Hosny MM, Fouad MM, Moneim NH. Association of interleukin-36a gene expression in Egyptian patients with systemic lupus erythematosus with organ involvement and disease activity. Egypt J Immunol 2021; 28(2): 75–84.

Files

Share

How to cite

Statistics