Serum Interleukin-17 and its Correlation with Anti-CCP antibodies, Vitamin D3, and Obesity in Rheumatoid Arthritis women Patients
Abstract
Background: Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease. Members of the IL-17 cytokine family have various biological functions, including enhancing defense against multiple pathogens while promoting inflammatory pathology during autoimmune disease. Additionally, it has been suggested that vitamin D may be connected to the etiology of RA. Therefore, this study aimed to assess serum IL-17 and vitamin D3 concentrations in RA women and determine how these levels relate to anti-CCP, obesity, and age.
Methods: This work included eighty women aged between (22-60) years. Sixty were afflicted with RA and attended the department of rheumatology and medical rehabilitation centre for rheumatic diseases at Rzgary teaching hospital-Erbil, Iraq, compared to twenty healthy women. The concentrations of Anti-CCP antibodies as a diagnostic test, Vitamin D3 and IL-17, were assessed by ELISA. The Mann-Whitney U test and normality were applied for the statistical analysis of the results. Also, the relationship between the study parameters was examined using Pearson's correlation. The ideal cutoff value for IL-17 with the highest sensitivity and specificity was detected using a Receiver Operating Characteristic (ROC) Curve.
Results: This study revealed that serum IL-17 levels were significantly higher in RA women than in the control group (p < 0.001) and that serum VD3 levels were significantly lower in RA women than in healthy controls. Seropositive anti-CCP Ab was found in about 42% of RA patients. The pro-inflammatory IL-17 serum level was positively correlated with vitamin D, age, and obesity in RA women. The best IL-17 cutoff for predicting the presence of RA was 69.5 pg/ML, with a sensitivity of 96% and a specificity of 75%.
Conclusion: In patients with RA, vitamin D deficiency was common and correlated with age. Consequently, a high level of suspicion is needed when assessing at-risk patients, particularly women who complain of vitamin D deficiency.
Full Text:
PDFReferences
Guo Q, Wang Y, Xu D, Nossent J, Pavlos NJ, et al. Rheumatoid arthritis: pathological mechanisms and modern pharmacologic therapies. Bone research, (2018); 6(1): 1-14.
Liu J, Gao J, Wu Z, Mi L, Li N, et al. Anti-citrullinated protein antibody generation, pathogenesis, clinical application and prospects. Frontiers in Medicine, (2022); 2853.
Smolen J, Aletaha D, McInnes I. Therapies for bone R. Lancet, (2016); 30173-30178.
Bullock J, Rizvi SA, Saleh AM, Ahmed SS, Do DP, et al. Rheumatoid arthritis: a brief overview of the treatment. Medical Principles and Practice, (2018); 27(6): 501-507.
Smith MH, Berman JR. What Is Rheumatoid Arthritis? JAMA, (2022); 327(12): 1194-1194.
Choy EH, Panayi GS. Cytokine pathways and joint inflammation in rheumatoid arthritis. New England Journal of Medicine, (2001); 344(12): 907-916.
Muller S, Radic M. Citrullinated autoantigens: from diagnostic markers to pathogenetic mechanisms. Clinical reviews in allergy & immunology, (2015); 49(2): 232-239.
Mun S, Lee J, Park A, Kim H-J, Lee Y-J, et al. Proteomics approach for the discovery of rheumatoid arthritis biomarkers using mass spectrometry. International journal of molecular sciences, (2019); 20(18): 4368.
Mun S, Lee J, Park M, Shin J, Lim M-K, et al. Serum biomarker panel for the diagnosis of rheumatoid arthritis. Arthritis Research & Therapy, (2021); 23(1): 1-10.
Almutairi K, Nossent J, Preen D, Keen H, Inderjeeth C. The global prevalence of rheumatoid arthritis: a meta-analysis based on a systematic review. Rheumatology international, (2021); 41(5): 863-877.
Malmström V, Catrina AI, Klareskog L. The immunopathogenesis of seropositive rheumatoid arthritis: from triggering to targeting. Nature Reviews Immunology, (2017); 17(1): 60-75.
Yap H-Y, Tee SZ-Y, Wong MM-T, Chow S-K, Peh S-C, et al. Pathogenic role of immune cells in rheumatoid arthritis: implications in clinical treatment and biomarker development. Cells, (2018); 7(10): 161.
Annunziato F, Cosmi L, Liotta F, Maggi E, Romagnani S. Type 17 T helper cells—origins, features and possible roles in rheumatic disease. Nature Reviews Rheumatology, (2009); 5(6): 325-331.
Hamad RS, Shnawa BH, Al-Ali SJ. Correlation between IL-10 as Cancer Biomarker and Demographic Characteristics of Colorectal Cancer Patients. Pharmaceutical Research International, (2021); 33(26B).
Jeffery LE, Raza K, Hewison M. Vitamin D in rheumatoid arthritis—towards clinical application. Nature Reviews Rheumatology, (2016); 12(4): 201-210.
Bragazzi NL, Watad A, Neumann SG, Simon M, Brown SB, et al. Vitamin D and rheumatoid arthritis: an ongoing mystery. Current opinion in
rheumatology, (2017); 29(4): 378-388.
Romão VC, Fonseca JE. Etiology and risk factors for rheumatoid arthritis: a state-of-the-art review. Frontiers in Medicine, (2021); 8.
Meena N, Chawla SPS, Garg R, Batta A, Kaur S. Assessment of vitamin D in rheumatoid arthritis and its correlation with disease activity. Journal of
natural science, biology, and medicine, (2018); 9(1): 54.
Shani WS, Shnawa B H, Waheda N E. Levels of Immunoglobulins and complements in sera of patients with toxoplasmosis. Basrah Journal of Scienec (B) Vol, (2012); 30(1): 72-77.
Khadim R, Al-Fartusie F. Evaluation of Liver Function and Lipid profiles in Iraqi patients with Rheumatoid Arthritis; 2021. IOP Publishing. pp. 012040.
Ridha A, Hussein S, AlJabban A, Gunay LM, Gorial FI, et al. The Clinical Impact of Seropositivity on Treatment Response in Patients with Rheumatoid Arthritis Treated with Etanercept: A Real-World Iraqi Experience. Open Access Rheumatology: Research and Reviews, (2022); 14113.
Hussein RH, MezherAl-Rayahi IA, Taha K. Rheumatoid factor isotypes in a sample of Iraqi rheumatoid arthritis patients. J Glob Pharma Technol, (2018); 10141-145.
Gr P, Dihingia P, Jha AK, Gadgade A, Agarwal D. Rheumatoid Arthritis Co-relation with Anti-CCP Antibodies with special reference to its Prevalence in Asymptomatic First-Degree Relatives. Mediterranean Journal of Rheumatology, (2022); 33(1): 42.
Dhaouadi T, Chahbi M, Haouami Y, Sfar I, Abdelmoula L, et al. IL-17A, IL-17RC polymorphisms and IL17 plasma levels in Tunisian patients with rheumatoid arthritis. PLoS One, (2018); 13(3): e0194883.
Rönnelid J, Wick MC, Lampa J, Lindblad S, Nordmark B, et al. Longitudinal analysis of citrullinated protein/peptide antibodies (anti-CP) during 5 year follow up in early rheumatoid arthritis: anti-CP status predicts worse disease activity and greater radiological progression. Annals of the rheumatic diseases,
(2005); 64(12): 1744-1749.
Aletaha D, Neogi T, Silman AJ, Funovits J, Felson DT, et al. 2010 rheumatoid arthritis classification criteria: an American College of Rheumatology/European League Against Rheumatism collaborative initiative. Arthritis & rheumatism, (2010); 62(9): 2569-2581.
Choi S-T, Lee K-H. Clinical management of seronegative and seropositive rheumatoid arthritis: a comparative study. PLoS One, (2018); 13(4): e0195550.
Martinez-Prat L, Nissen MJ, Lamacchia C, Bentow C, Cesana L, et al. comparison of serological biomarkers in rheumatoid arthritis and their combination to improve diagnostic performance. Frontiers in immunology, (2018); 91113.
Hamad BA. Relationship between vitamin D3 level and rheumatoid arthritis patients attending Rizgary Teaching Hospital in Erbil city. Zanco Journal of Medical Sciences (Zanco J Med Sci), (2017); 21(2): 1736-1742.
Sukharani N, Dev K, Rahul F, Bai P, Ali A, et al. Association between rheumatoid arthritis and serum vitamin D levels. Cureus, (2021); 13(9).
Harrison SR, Li D, Jeffery LE, Raza K, Hewison M. Vitamin D, autoimmune disease and rheumatoid arthritis. Calcified tissue international, (2020); 106(1): 58-75.
Merlino LA, Curtis J, Mikuls TR, Cerhan JR, Criswell LA, et al. Vitamin D intake is inversely associated with rheumatoid arthritis: results from the Iowa Women's Health Study. Arthritis & Rheumatism: Official Journal of the American College of Rheumatology, (2004); 50(1): 72-77.
Dupuis ML, Pagano MT, Pierdominici M, Ortona E. The role of vitamin D in autoimmune diseases: could sex make the difference? Biology of sex differences, (2021); 12(1): 1-12.
Qu C, Hou Y, Bi Y, Han Q, Jiao C, et al. Diagnostic values of serum IL-10 and IL-17 in rheumatoid arthritis and their correlation with serum 14-3-3η protein. Eur Rev Med Pharmacol Sci, (2019); 23(5): 1899-1906.
Atwa SE, Azab MM, Mohamed MS. Serum Interleukin-17 Level in Patients with Rheumatoid Arthritis and its Relation to Disease Activity. Zagazig University Medical Journal, (2020); 26(1): 87-93.
Dissanayake K, Jayasinghe C, Wanigasekara P, Sominanda A. Potential applicability of cytokines as biomarkers of disease activity in rheumatoid arthritis: Enzyme-linked immunosorbent spot assay-based evaluation of TNF-α, IL-1β, IL-10 and IL-17A. PloS one, (2021); 16(1): e0246111.
Robert M, Miossec P. IL-17 in rheumatoid arthritis and precision medicine: from synovitis expression to circulating bioactive levels. Frontiers in medicine, (2019); 5364.
Shnawa BH, Al-Ali SJ, Ahmad HF, Essa SA. An Investigative Study of Smoking Effects on IL-31 Levels and Leukocyte differential counts in Humans. Annals of Tropical Medicine and Public Health. (2020); 23(11).
Mills KH. IL-17 and IL-17-producing cells in protection versus pathology. Nature Reviews Immunology, (2022); 1-17.
Refbacks
- There are currently no refbacks.