Investigating the association of vitamin D levels with RF and HMGB1 in Rheumatoid arthritis patients in Basra, Iraq

Abstract

Background: Rheumatoid arthritis (RA) is autoimmune disease characterized by swollen joints and the presence of autoantibodies. Many factors can affect the susceptibility of a person to this autoimmune disease, one of these factors is the level of vitamin D (VD3). The aim of the study is investigating the relationships of VD3, RF and HMGB1 in RA patients in Basra. Materials and Methods: A total of 154 participants were included RA patients (n=113) and healthy control (HC) (n=41) from both sexes, age range 23-75 years. The sera of RA patients and HC were tested for the level of Rheumatoid Factors (RF) included (IgG and IgM), VD3 and Human HMGB1 protein measurement by ELISA. Results: Our results showed that the level of RF were significantly higher and VD3 was significantly lower in RA patients in compare with HC. Furthermore, serum HMGB1 levels were higher in RA patients without treatment, but decreases upon therapy in patients while it was low in HC. A significant differences noticed in serum HMGB1 levels in RA patients depended on the types of drugs. Positive correlation between VD3, HMGB1 and the disease progress, while negative correlations were found between VD3, RF and HMGB1. Conclusion: The status of VD3 in RA patients living in Basra and its relation to the levels of RF and the pro inflammatory mediator HMGB1, documenting that VD3 deficiency play a role in causing the inflammation during RA.

References

  • Aletaha, D., & Smolen, J. S. (2018). Diagnosis and management of rheumatoid arthritis: a review. Jama, 320(13), 1360-1372.
  • Al-Herz, A., Al-Awadhi, A., Saleh, K., Al-Kandari, W., Hasan, E., Ghanem, A., ... & Khadrawy, A. (2016). A comparison of rheumatoid arthritis patients in Kuwait with other populations: results from the KRRD registry. Journal of Advances in Medicine and Medical Research, 1-11.‏
  • Alpízar-Rodríguez, D., Pluchino, N., Canny, G., Gabay, C., & Finckh, A. (2017). The role of female hormonal factors in the development of rheumatoid arthritis. Rheumatology, 56(8), 1254-1263.‏
  • Al-Salih, M. W., & Selman, A. N. (2015). Evaluation of heat shock proteins 70 (HSP70) and some risk factors in sera of rheumatoid arthritis patients in Thi-Qar province. Al-Nahrain Journal of Science, 18(1), 123-129.
  • Altieri, B., Muscogiuri, G., Barrea, L., Mathieu, C., Vallone, C. V., Mascitelli, L., ... & Savastano, S. (2017). Does vitamin D play a role in autoimmune endocrine disorders? A proof of concept. Reviews in Endocrine and Metabolic Disorders, 18(3), 335-346.‏
  • Arnson, Y., Amital, H., & Shoenfeld, Y. (2007). Vitamin D and autoimmunity: new aetiological and therapeutic considerations. Annals of the rheumatic diseases, 66(9), 1137-1142.‏
  • Azzeh, F. S. (2012). Relationship between vitamin D and rheumatoid arthritis disease. Pakistan Journal of Nutrition, 11(3), 293.‏
  • Børretzen, M., Chapman, C., Natvig, J. B., & Thompson, K. M. (1997). Differences in mutational patterns between rheumatoid factors in health and disease are related to variable heavy chain family and germ‐line gene usage. European journal of immunology, 27(3), 735-741.‏
  • Brown, D. M., Goubet, F., Wong, V. W., Goodacre, R., Stephens, E., Dupree, P., & Turner, S. R. (2008). Comparison of five xylan synthesis mutants reveals new insight into the mechanisms of xylan synthesis. The Plant Journal, 52(6), 1154-1168.‏
  • Bugatti, S., Vitolo, B., Caporali, R., Montecucco, C., & Manzo, A. (2014). B cells in rheumatoid arthritis: from pathogenic players to disease biomarkers. BioMed research international, 2014.‏
  • Cantorna, M. T., Snyder, L., Lin, Y. D., & Yang, L. (2015). Vitamin D and 1, 25 (OH) 2D regulation of T cells. Nutrients, 7(4), 3011-3021.
  • Chang, M. H., & Nigrovic, P. A. (2019). Antibody-dependent and-independent mechanisms of inflammatory arthritis. JCI insight, 4(5).
  • Chiang, H. C. (2017). Comparison of Hybridization in DNA Brushes and in Solution (Doctoral dissertation, Polytechnic Institute of New York University).‏
  • Chun, R. F., Liu, P. T., Modlin, R. L., Adams, J. S., & Hewison, M. (2014). Impact of vitamin D on immune function: lessons learned from genome-wide analysis. Frontiers in physiology, 5, 151.
  • Deane, K. D., Demoruelle, M. K., Kelmenson, L. B., Kuhn, K. A., Norris, J. M., & Holers, V. M. (2017). Genetic and environmental risk factors for rheumatoid arthritis. Best practice & research Clinical rheumatology, 31(1), 3-18.‏
  • Di Rosa, M., Malaguarnera, M., Nicoletti, F., & Malaguarnera, L. (2011). Vitamin D3: a helpful immuno‐modulator. Immunology, 134(2), 123-139.‏
  • Disanto, G., & Ramagopalan, S. V. (2010). Vitamin D: shining a light on autoimmune disease. International Journal of Clinical Rheumatology, 5(6), 605.‏
  • Dubois, B., Kobelt, G., Berg, J., Capsa, D., Gannedahl, M., & European Multiple Sclerosis Platform. (2017). New insights into the burden and costs of multiple sclerosis in Europe: Results for Belgium. Multiple Sclerosis Journal, 23(2_suppl), 29-40.‏
  • Evankovich, J., Cho, S. W., Zhang, R., Cardinal, J., Dhupar, R., Zhang, L., ... & Tsung, A. (2010). High mobility group box 1 release from hepatocytes during ischemia and reperfusion injury is mediated by decreased histone deacetylase activity. Journal of Biological Chemistry, 285(51), 39888-39897.‏
  • Gamerith, F., Zlabinger, G. J., Scherak, O., Kolarz, G., Schemper, M., Heinzl, H., & Menzel, J. E. (1993). Differences in anti-Fab antibodies in adult and late onset rheumatoid arthritis. Rheumatology international, 13(3), 107-112.‏
  • Garfinkel, R. J., Dilisio, M. F., & Agrawal, D. K. (2017). Vitamin D and its effects on articular cartilage and osteoarthritis. Orthopaedic Journal of Sports Medicine, 5(6), 2325967117711376.‏
  • Hajjaj-Hassouni, N., Mawani, N., Allali, F., Rkain, H., Hassouni, K., Hmamouchi, I., & Dougados, M. (2017). Evaluation of vitamin D status in rheumatoid arthritis and its association with disease activity across 15 countries:”The COMORA Study”. International journal of rheumatology, 2017.‏
  • Haque, U. J., Bathon, J. M., & Giles, J. T. (2012). Association of vitamin D with cardiometabolic risk factors in rheumatoid arthritis. Arthritis care & research, 64(10), 1497-1504.‏
  • Holick, M. F., & Chen, T. C. (2008). Vitamin D deficiency: a worldwide problem with health consequences. The American journal of clinical nutrition, 87(4), 1080S-1086S.‏
  • Hussein, R.H., MezherAl-Rayahi, I.A., Taha,K.(2018). Rheumatoid factor isotypes in a sample of Iraqi rheumatoid arthritis patients, J. Glob. Pharma Technol. 10 141–145.
  • Ihsan, M.A.A. Chiad1*, A. Hanaa S.Yossef, Muntadher A. Al-Saidi2,(2015). Evaluation of Some Immunological Markers in the Rheumatoid Arthritis Patients, 56 7 2488–2493.
  • Ingegnoli, F., Castelli, R., & Gualtierotti, R. (2013). Rheumatoid factors: clinical applications. Disease markers, 35.‏
  • Kostoglou-Athanassiou, I., Athanassiou, P., Lyraki, A., Raftakis, I., & Antoniadis, C. (2012). Vitamin D and rheumatoid arthritis. Therapeutic advances in endocrinology and metabolism, 3(6), 181-187.‏
  • Lee, Y. H., & Bae, S. C. (2016). Vitamin D level in rheumatoid arthritis and its correlation with the disease activity: a meta-analysis. Clin Exp Rheumatol, 34(5), 827-833.‏
  • Li, Y. B., Xu, P., Xu, K., Cai, Y. S., Sun, M. Y., Yang, L., ... & Lu, S. M. (2016). Methotrexate affects HMGB1 expression in rheumatoid arthritis, and the downregulation of HMGB1 prevents rheumatoid arthritis progression. Molecular and cellular biochemistry, 420(1-2), 161-170.‏
  • Lin, J., Liu, J., Davies, M. L., & Chen, W. (2016). Serum vitamin D level and rheumatoid arthritis disease activity: review and meta-analysis. PloS one, 11(1), e0146351.‏
  • Liu, W., Zhang, L., Xu, H. J., Li, Y., Hu, C. M., Yang, J. Y., & Sun, M. Y. (2018). The anti-inflammatory effects of vitamin D in tumorigenesis. International journal of molecular sciences, 19(9), 2736.
  • Lu, M., Yu, S., Xu, W., Gao, B., & Xiong, S. (2015). HMGB1 promotes systemic lupus erythematosus by enhancing macrophage inflammatory response. Journal of immunology research, 2015.‏
  • Magna, M., & Pisetsky, D. S. (2014). The role of HMGB1 in the pathogenesis of inflammatory and autoimmune diseases. Molecular medicine, 20(1), 138-146.‏
  • Makinodan, T., & Kay, M. M. (1980). Age influence on the immune system. In Advances in immunology (Vol. 29, pp. 287-330). Academic Press.‏
  • Malm, K. Bremander, A. Arvidsson,B. Andersson, M.L.E. Bergman,S. Larsson,(2016). I. The influence of lifestyle habits on quality of life in patients with established rheumatoid arthritis - A constant balancing between ideality and reality, Int. J. Qual. Stud. Health Well-Being. 11 https://doi.org/10.3402/qhw.v11.30534.
  • Mayyadah R.H.A.-J. & Rashid, M.H.A. H.(2017). Plasma microRNA-16 expression as a potential biomarker for disease assessment in newly diagnosed theumatoid arthritis patients, IJABR, VOL.7 2017 257-262.
  • Meena, N., Chawla, S. P. S., Garg, R., Batta, A., & Kaur, S. (2018). Assessment of vitamin D in rheumatoid arthritis and its correlation with disease activity. Journal of natural science, biology, and medicine, 9(1), 54.‏
  • Meng, X. H., Wang, Z., Zhang, X. N., Xu, J., & Hu, Y. C. (2018). Rheumatoid Arthritis of Knee Joints: MRI–Pathological Correlation. Orthopaedic Surgery, 10(3), 247-254.
  • Mukhtar, M., Sheikh, N., Suqaina, S. K., Batool, A., Fatima, N., Mehmood, R., & Nazir, S. (2019). Vitamin D receptor gene polymorphism: an important predictor of arthritis development. BioMed Research International, 2019.‏
  • Muss, T. Q., AL-Faham, M., & Gorial, F. I.(2018). Assessment of Serum Galectin-8 in Iraqi Patients with Rheumatoid arthritis.‏
  • Nowak, A., Boesch, L., Andres, E., Battegay, E., Hornemann, T., Schmid, C., ... & Krayenbuehl, P. A. (2016). Effect of vitamin D3 on self-perceived fatigue: A double-blind randomized placebo-controlled trial. Medicine, 95(52).‏
  • Ohajianya, D. O., Okwara, M. O., Ugwu, J. N., Tim Ashama, A., Mbah, R. O., & Dike, N. F. (2016). Productivity of Farmland Values in Food Crop Production in the Natural Disasters Prone Areas of Imo State, Nigeria. International Journal of Sustainable Agricultural Research, 3(2), 42-48
  • Pérez-Hernández, N., Aptilon-Duque, G., Nostroza-Hernández, M. C., Vargas-Alarcón, G., Rodríguez-Pérez, J. M., & Blachman-Braun, R. (2016). Vitamin D and its effects on cardiovascular diseases: a comprehensive review. The Korean journal of internal medicine, 31(6), 1018.‏
  • Pilzweger, C., & Holdenrieder, S. (2015). Circulating HMGB1 and RAGE as clinical biomarkers in malignant and autoimmune diseases. Diagnostics, 5(2), 219-253.‏
  • Radner, H., Smolen, J. S., & Aletaha, D. (2011). Comorbidity affects all domains of physical function and quality of life in patients with rheumatoid arthritis. Rheumatology, 50(2), 381-388.
  • Rocha, S. D. B., Baldo, D. C., & Andrade, L. E. C. (2019). Clinical and pathophysiologic relevance of autoantibodies in rheumatoid arthritis. Advances in Rheumatology, 59.
  • Schierbeck, H. Pullerits, R. Pruunsild, C. Fischer,M. D. Holzinger, Å. Laestadius, E. Sundberg, Harris, H.E. (2013).HMGB1 levels are increased in patients with juvenile idiopathic arthritis, correlate with early onset of disease,,andare independent of disease duration, J. Rheumatol. 40 1604–1613. https://doi.org/10.3899/jrheum.120987.
  • Solidoro, P., Bellocchia, M., Aredano, I., Mattei, A., Pivetta, E., Patrucco, F., ... & Bucca, C. (2017). Asthmatic patients with vitamin D deficiency have decreased exacerbations after vitamin replacement. Nutrients, 9(11), 1234.‏
  • Song, Y. W., & Kang, E. H. (2010). The pathogenic role of rheumatoid factor in rheumatoid arthritis. International Journal of Clinical Rheumatology, 5(6), 651.
  • Tsung, A., Klune, J. R., Zhang, X., Jeyabalan, G., Cao, Z., Peng, X., ... & Billiar, T. R. (2007). HMGB1 release induced by liver ischemia involves Toll-like receptor 4–dependent reactive oxygen species production and calcium-mediated signaling. The Journal of experimental medicine, 204(12), 2913-2923.‏
  • van Etten, E., & Mathieu, C. (2005). Immunoregulation by 1, 25-dihydroxyvitamin D3: basic concepts. The Journal of steroid biochemistry and molecular biology, 97(1-2), 93-101.‏
  • Walker, S. E., & Ranatunga, S. K. (2006). Rheumatoid arthritis: A review. Missouri medicine, 103(5), 539-544.
  • Wang, H., Bloom, O., Zhang, M., Vishnubhakat, J. M., Ombrellino, M., Che, J., ... & Manogue, K. R. (1999). HMG-1 as a late mediator of endotoxin lethality in mice. Science, 285(5425), 248-251.‏
  • Wang, W., Wu, A., Zhou, Y., Wang, Y., & Cao, K. (2017). Association between Vitamin D Receptor polymorphisms and rheumatoid arthritis risk: a meta-analysis. International Journal of Clinical & Experimental Medicine, 10(2).‏
  • Yuen, E. Y., Liu, W., Karatsoreos, I. N., Ren, Y., Feng, J., McEwen, B. S., & Yan, Z. (2011). Mechanisms for acute stress-induced enhancement of glutamatergic transmission and working memory. Molecular psychiatry, 16(2), 156-170.‏

License

This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.