Level of Interleukin-35, Interleukin-36, and the Interleukin-35/Interleukin-36 Ratio in Juvenile Idiopathic Arthritis

Authors

  • Qudus W. Jamal Department of Microbiology, College of Medicine, Nahrain University, Baghdad, Iraq
  • Ghassaq Alubaidi Medical Research Unit, College of Medicine, Nahrain University, Baghdad, Iraq https://orcid.org/0000-0002-7287-9398
  • Yasmin Humadi Department of Internal Medicine, College of Medicine, Nahrain University, Baghdad, Iraq

DOI:

https://doi.org/10.3889/oamjms.2021.6671

Keywords:

Juvenile rheumatoid arthritis, Interleukin-35, Interleukin-36, Interleukin-35/interleukin-36 ratio, Juvenile Arthritis Disease Activity Score-27

Abstract

BACKGROUND: Cytokines are inflammatory mediators that regulate multiple processes potentially implicated in inflammation and autoimmunity.

AIM: This study aimed to investigate the levels of circulating interleukin (IL)-35, IL-36, and IL-35/IL-36 ratio in Juvenile Idiopathic Arthritis (JIA) patients.

METHODS: Fifty-one patients categorized based on the International League of Associations for Rheumatology classification criteria were enrolled, along with 46 healthy controls. Disease activity assessment was conducted according to the Juvenile Arthritis Disease Activity Score (JADAS-27) system. Serum cytokine levels were determined using the sandwich enzyme-linked immunosorbent assay.

RESULTS: Compared to controls, the serum levels of IL-36 were significantly higher among JIA children (p = 0.002), and serum IL-35 levels and the IL-35/IL-36 ratio were significantly lower in the patients (p = 0.002, p < 0.001, respectively). Furthermore, the IL-35/IL-36 serum ratio, but not the absolute IL levels, correlated positively with the JADAS-27, giving a good indication of the disease outcome. Further, the IL-35/IL-36 serum ratio showed higher sensitivity and specificity compared to the absolute cytokine levels.

CONCLUSION: A significant change in the circulating IL-35 and IL-36 levels and an imbalance in the IL35/IL36 ratio occur in JIA. This study is a novel attempt to explore the role of IL-35 and IL-36 in JIA; further studies are required to support our results. The IL-35/Il-36 ratio is a promising immunological marker to predict, diagnose, and monitor JIA.

Downloads

Download data is not yet available.

Metrics

Metrics Loading ...

Plum Analytics Artifact Widget Block

References

Bridges JM, Mellins ED, Cron RQ. Recent progress in the treatment of non-systemic juvenile idiopathic arthritis. Fac Rev. 2021;10:23. https://doi.org/10.12703/r/10-23 PMid:33718940

Bluestone JA, Bour-Jordan H. Current and future immunomodulation strategies to restore tolerance in autoimmune diseases. Cold Spring Harb Perspect Biol. 2021;4(11):a007542. https://doi.org/10.1101/cshperspect.a007542 PMid:23125012

Wareth G, Brandt C, Sprague LD, Neubauer H, Pletz MW. Spatio-temporal distribution of Acinetobacter baumannii in Germany-a comprehensive systematic review of studies on resistance development in humans (2000-2018). Microorganisms. 2020;8(3):375. https://doi.org/10.3390/microorganisms8030375 PMid:32155886

Poddighe D, Romano M, Gattinara M, Gerloni V. Biologics for the treatment of juvenile idiopathic arthritis. Curr Med Chem. 2018;25(42):5860-93. https://doi.org/10.2174/0929867325666180522085716 PMid:29788871

Fischer R, Kontermann RE, Pfizenmaier K. Selective targeting of TNF receptors as a novel therapeutic approach. Front Cell Dev Biol. 2020;8:401. https://doi.org/10.3389/fcell.2020.00401 PMid:32528961

Lainka E, Baehr M, Raszka B, Haas JP, Hügle B, Fischer N, et al. Experiences with IL-1 blockade in systemic juvenile idiopathic arthritis-data from the German AID-registry. Pediatr Rheumatol. 2021;19(1):38. https://doi.org/10.1186/s12969-021-00510-8 PMid:33752669

Vijatov-Djuric G, Doronjski A, Mitic I, Brkic S, Barisic N. Interleukin-17A levels increase in serum of children with juvenile idiopathic arthritis. Arch Rheumatol. 2017;32(3):234-43. https://doi.org/10.5606/archrheumatol.2017.6067 PMid:30375522

Catalan-Dibene J, McIntyre LL, Zlotnik A. Interleukin 30 to interleukin 40. J Interferon Cytokine Res. 2018;38(10):423-39. https://doi.org/10.1089/jir.2018.0089 PMid:30328794

Choi J, Leung PSC, Bowlus C, Gershwin ME. IL-35 and autoimmunity: A comprehensive perspective. Clin Rev Allergy Immunol. 2015;49(3):327-32. https://doi.org/10.1007/s12016-015-8468-9 PMid:25619872

Niedbala W, Wei XQ, Cai B, Hueber AJ, Leung BP, McInnes IB, et al. IL-35 is a novel cytokine with therapeutic effects against collagen-induced arthritis through the expansion of regulatory T cells and suppression of Th17 cells. Eur J Immunol. 2007;37(11):3021-9. https://doi.org/10.1002/eji.200737810 PMid:17874423

Ding L, Wang X, Hong X, Lu L, Liu D. IL-36 cytokines in autoimmunity and inflammatory disease. Oncotarget. 2018;9(2):2895-901. https://doi.org/10.18632/oncotarget.22814 PMid:29416822

Han Y, Huard A, Mora J, da Silva P, Brüne B, Weigert A. IL-36 family cytokines in protective versus destructive inflammation. Cell Signal. 2020;75:109773. https://doi.org/10.1016/j.cellsig.2020.109773 PMid:32898612

Boutet MA, Nerviani A, Pitzalis C. IL-36, IL-37, and IL-38 cytokines in skin and joint inflammation: A comprehensive review of their therapeutic potential. Int J Mol Sci. 2019;20(6):1257. https://doi.org/10.3390/ijms20061257 PMid:30871134

Frey S. The novel cytokine interleukin-36α is expressed in psoriatic and rheumatoid arthritis synovium. Ann Rheum Dis. 2013;72(9):1569-74. https://doi.org/10.1136/annrheumdis-2012-202264 PMid:23268368

Mourão AF, Santos MJ, Melo-Gomes J, Martins FM, Costa JA, Ramos F, et al. Using the juvenile arthritis disease activity score based on erythrocyte sedimentation rate or C-reactive protein level: Results from the Portuguese register. Arthritis Care Res (Hoboken). 2014;66(4):585-91. https://doi.org/10.1002/acr.22215 PMid:25354266

Ćalasan MB, de vries LD, Vastert SJ, Heijstek MW, Wulffraat NM. Interpretation of the Juvenile Arthritis Disease Activity Score: Responsiveness, clinically important differences and levels of disease activity in prospective cohorts of patients with juvenile idiopathic arthritis. Rheumatology (Oxford). 2014;53(2):307-12. https://doi.org/10.1093/rheumatology/ket310 PMid:24162034

Consolaro A, Ruperto N, Bazso A, Pistorio A, Magni-Manzoni S, Filocamo G, et al. Development and validation of a composite disease activity score for juvenile idiopathic arthritis. Arthritis Rheum. 2009;61(5):658-66. https://doi.org/10.1002/art.24516 PMid:19405003

Fish J, Lipton J, Lanzkowsky P, editors. Lanzkowsky’s Manual of Pediatric Hematology and Oncology. Amsterdam, Netherlands: Elsevier Inc.; 2016. https://doi.org/10.1016/b978-0-12-801368-7.00044-2

Li Y, Wang Y, Liu H, Ding K, Hao S, Shao Y, et al. Lower level of IL-35 and its reduced inhibition in Th17 cells in patients with bone marrow mononuclear cells Coombs test-positive hemocytopenia. Mol Med Rep. 2018;17(2):2973-81. https://doi.org/10.3892/mmr.2017.8252 PMid:29257310

Zhang J, Zhang Y, Wang Q, Li C, Deng H, Si C, et al. Interleukin-35 in immune-related diseases: Protection or destruction. Immunology. 2019;157(1):13-20. https://doi.org/10.1111/imm.13044 PMid:30681737

Guan SY, Leng RX, Khan MI, Qureshi H, Li XP, Ye DQ, et al. Interleukin-35: A potential therapeutic agent for autoimmune Diseases. Inflammation. 2017;40(1):303-10. https://doi.org/10.1007/s10753-016-0453-9 PMid:27696334

Bridgewood C, Alase A, Watad A, Wittmann M, Cuthbert R, McGonagle D. The IL-23p19/EBI3 heterodimeric cytokine termed IL-39 remains a theoretical cytokine in man. Inflamm Res. 2019;68(6):423-6. https://doi.org/10.1007/s00011-019-01235-x PMid:30989239

Zhao J, Lu Q, Liu Y, Shi Z, Hu L, Zeng Z, et al. Th17 cells in inflammatory bowel disease: Cytokines, plasticity, and therapies. J Immunol Res. 2021;2021:8816041. https://doi.org/10.1093/rheumatology/keu528 PMid:33553436

Nakano S, Morimoto S, Suzuki S, Tsushima H, Yamanaka K, Sekigawa I, et al. Immunoregulatory role of IL-35 in T cells of patients with rheumatoid arthritis. Rheumatology (Oxford). 2015;54(8):1498-506. PMid:25731770

Schmitt V, Hahn M, Kästele V, Wagner O, Wiendl M, Derer A, et al. Interleukin-36 receptor mediates the crosstalk between plasma cells and synovial fibroblasts. Eur J Immunol. 2017;47(12):2101-12. https://doi.org/10.1002/eji.201646788 PMid:28857172

Yuan ZC, Xu WD, Liu XY, Liu XY, Huang AF, Su LC. Biology of il-36 signaling and its role in systemic inflammatory diseases. Front Immunol. 2019;10:2532. https://doi.org/10.3389/fimmu.2019.02532 PMid:31736959

Lab Test: White Blood Cell Count, WBC. Available from: http://www.genes-environment-inflammation.de/basic-page/grants-funding-after-doctorate. [Last access on 2021 Feb 14].

Liang PY, Diao LH, Huang CY, Lian RC, Chen X, Li GG, et al. The pro-inflammatory and anti-inflammatory cytokine profile in peripheral blood of women with recurrent implantation failure. Reprod Biomed Online. 2015;31(6):823-6. https://doi.org/10.1016/j.rbmo.2015.08.009 PMid:26371706

Chou CW, Lin FC, Tsai HC, Chang SC. The importance of pro-inflammatory and anti-inflammatory cytokines in Pneumocystis jirovecii pneumonia. Med Mycol. 2013;51(7):704-12. https://doi.org/10.3109/13693786.2013.772689 PMid:23488973

Chung SJ, Kwon YJ, Park MC, Park YB, Lee SK. The correlation between increased serum concentrations of interleukin-6 family cytokines and disease activity in rheumatoid arthritis patients. Yonsei Med J. 2011;52(1):113-20. https://doi.org/10.3349/ymj.2011.52.1.113 PMid:21155043

Downloads

Published

2021-09-02

How to Cite

1.
Jamal QW, Alubaidi G, Humadi Y. Level of Interleukin-35, Interleukin-36, and the Interleukin-35/Interleukin-36 Ratio in Juvenile Idiopathic Arthritis. Open Access Maced J Med Sci [Internet]. 2021 Sep. 2 [cited 2024 Apr. 20];9(A):741-7. Available from: https://oamjms.eu/index.php/mjms/article/view/6671