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Serum levels of adiponectin and vitamin D correlate with activity of Rheumatoid Arthritis

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Abstract

Rheumatoid arthritis (RA) is a chronic inflammatory disease in which numerous cells and mediators affect inflammatory conditions and disease severity. To compare the serum levels of adiponectin, vitamin D, copper, and zinc in patients with RA and to investigate the relationship between these parameters and RA severity. Ninety patients with RA and 30 healthy controls participated in this cross-sectional case-control study between November 2016 and April 2017; according to the ACR/EULAR criteria for RA. Serum levels of adiponectin were determined by ELISA; copper and zinc by colorimetric spectrophotometry; and vitamin D by HPLC. Kruskal-Wallis and Spearman tests were performed using SPSS software and data were depicted by GraphPad Prism software. Compared with healthy controls, the serum level of adiponectin was significantly increased, whereas vitamin D was significantly decreased in patients with RA. Adiponectin and vitamin D levels were inversely correlated in RA subgroups (P < 0.001, r = − 0.410). Adiponectin and vitamin D correlated with RA severity. Furthermore, no significant difference was found in copper and zinc levels between RA groups and controls. The definitive roles of adiponectin, vitamin D, copper, and zinc are not completely determined in RA development. Based on disease activity, these parameters can modulate inflammatory conditions, thus they have the potential to be used as promising therapeutic biomarkers to follow up the severity of disease, as well as the progression and treatment success in patients with RA.

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Abbreviations

CRP:

C-reactive protein

DAS28:

Disease activity score

ESR:

Erythrocyte sedimentation rate

ELISA:

Enzyme-linked immunosorbent assay

HPLC:

High-performance liquid chromatography

IL:

Interleukin

MMP:

Matrix metalloproteinase

NF-κB:

Nuclear factor-kappa B

RA:

Rheumatoid arthritis

SLE:

Systemic lupus erythematosus

TNF:

Tumor necrosis factor

References

  1. Kontny E, Plebanczyk M, Lisowska B, Olszewska M, Maldyk P, Maslinski W (2011) Comparison of rheumatoid articular adipose and synovial tissue reactivity to proinflammatory stimuli: contribution to adipocytokine network. Ann Rheum Dis 71:262–267

    Article  CAS  PubMed  Google Scholar 

  2. Uhlig T, Moe RH, Kvien TK (2014) The burden of disease in rheumatoid arthritis. Pharmacoeconomics 32:841–851

    Article  PubMed  Google Scholar 

  3. Coelho M, Oliveira T, Fernandes R (2013) Biochemistry of adipose tissue: an endocrine organ. Arch Med Sci 9:191

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Ouchi N, Walsh K (2007) Adiponectin as an anti-inflammatory factor. Clin Chim Acta 380:24–30

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Lee Y-A, Ji H-I, Lee S-H, Hong S-J, Yang H-I, Yoo MC et al (2014) The role of adiponectin in the production of IL-6, IL-8, VEGF and MMPs in human endothelial cells and osteoblasts: implications for arthritic joints. Exp Mol Med 46:e72

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Meyer M, Sellam J, Fellahi S, Kotti S, Bastard J-P, Meyer O et al (2013) Serum level of adiponectin is a surrogate independent biomarker of radiographic disease progression in early rheumatoid arthritis: results from the ESPOIR cohort. Arthritis Res Ther 15:R210

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Atherton K, Berry DJ, Parsons T, Macfarlane GJ, Power C, Hyppönen E (2009) Vitamin D and chronic widespread pain in a white middle-aged British population: evidence from a cross-sectional population survey. Ann Rheum Dis 68:817–822

    Article  CAS  PubMed  Google Scholar 

  8. Herly M, Stengaard-Pedersen K, Vestergaard P, Østergaard M, Junker P, Hetland ML et al (2018) The D-vitamin metabolite 1, 25 (OH) 2D in serum is associated with disease activity and Anti-Citrullinated Protein Antibodies in active and treatment naïve, early Rheumatoid Arthritis Patients. Scand J Immunol 88:e12704

    Article  CAS  PubMed  Google Scholar 

  9. He X-J, Ding Y, Xiang W, Dang X-Q (2016) Roles of 1, 25 (OH) 2D3 and vitamin D receptor in the pathogenesis of rheumatoid arthritis and systemic lupus erythematosus by regulating the activation of CD4 + T cells and the PKCδ/ERK signaling pathway. Cell Physiol Biochem 40:743–756

    Article  CAS  PubMed  Google Scholar 

  10. Turnlund JR, Jacob RA, Keen CL, Strain J, Kelley DS, Domek JM et al (2004) Long-term high copper intake: effects on indexes of copper status, antioxidant status, and immune function in young men. Am J Clin Nutr 79:1037–1044

    Article  CAS  PubMed  Google Scholar 

  11. Muñoz C, López M, Olivares M, Pizarro F, Arredondo M, Araya M (2005) Differential response of interleukin-2 production to chronic copper supplementation in healthy humans. Eur Cytokine Netw 16:261–265

    PubMed  Google Scholar 

  12. Teles M, MacKenzie S, Boltana S, Callol A, Tort L (2011) “Gene expression and TNF-alpha secretion profile in rainbow trout macrophages following exposures to copper and bacterial lipopolysaccharide. Fish Shellfish Immunol 30:340–346

    Article  CAS  PubMed  Google Scholar 

  13. Yang T-H, Yuan T-H, Hwang Y-H, Lian I-B, Meng M, Su C-C (2015) Increased inflammation in rheumatoid arthritis patients living where farm soils contain high levels of copper. J Formosan Med Assoc 115:991–996

    Article  CAS  PubMed  Google Scholar 

  14. Overbeck S, Rink L, Haase H (2008) Modulating the immune response by oral zinc supplementation: a single approach for multiple diseases. Arch Immunol Ther Exp 56: 15–30,

    Article  CAS  Google Scholar 

  15. Amancio OS, Chaud DA, Yanaguibashi G, Hilário ME (2003) Copper and zinc intake and serum levels in patients with juvenile rheumatoid arthritis. Eur J Clin Nutr 57:706–712

    Article  CAS  Google Scholar 

  16. Soylak M, Kirnap M (2001) Serum copper and zinc concentrations of patients with rheumatoid arthritis from Kayseri-Turkey. Fresenius Environ Bull 10:409–410

    CAS  Google Scholar 

  17. Aletaha D, Neogi T, Silman AJ, Funovits J, Felson DT, Bingham CO et al (2010) 2010 rheumatoid arthritis classification criteria: an American College of Rheumatology/European League Against Rheumatism collaborative initiative. Arthritis Rheumatology 62:2569–2581

    Article  Google Scholar 

  18. Anderson J, Caplan L, Yazdany J, Robbins ML, Neogi T, Michaud K et al (2012) Rheumatoid arthritis disease activity measures: american College of Rheumatology recommendations for use in clinical practice. Arthritis Care Res 64:640–647

    Article  Google Scholar 

  19. Seif F, Khoshmirsafa M, Mousavi M, Beshkar P, Rafeian-Kopaei M, Bagheri N et al (2014) Interleukin-21 receptor might be a novel therapeutic target for the treatment of rheumatoid arthritis. J Exp Clin Med 6:57–61

    Article  CAS  Google Scholar 

  20. Mohsenzadegan M, Fayazi MR, Abdolmaleki M, Bakhshayesh M, Seif F, Mousavizadeh K (2015) Direct immunomodulatory influence of IFN-β on human astrocytoma cells. Immunopharmacol Immunotoxicol 37:214–219

    Article  CAS  PubMed  Google Scholar 

  21. Seif F, Khoshmirsafa M, Aazami H, Mohsenzadegan M, Sedighi G, Bahar M (2017) The role of JAK-STAT signaling pathway and its regulators in the fate of T helper cells. Cell Commun Signal 15:23

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Lee YH, Bae SC (2017) Circulating adiponectin and visfatin levels in rheumatoid arthritis and their correlation with disease activity: a meta-analysis. Int J Rheum Dis 21:664-672

    PubMed  Google Scholar 

  23. Dini AA, Wang P, Ye D-Q (2017) Serum adiponectin levels in patients with systemic lupus erythematosus: a meta-analysis. J Clin Rheumatol 23:361–367

    Article  PubMed  Google Scholar 

  24. Shehzad W, Iqbal O, Shehzad, Lee YS (2012) Adiponectin: regulation of its production and its role in human diseases. Hormones (Athens) 11:8–20

    Article  Google Scholar 

  25. Tang C-H, Chiu Y-C, Tan T-W, Yang R-S, Fu W-M (2007) Adiponectin enhances IL-6 production in human synovial fibroblast via an AdipoR1 receptor, AMPK, p38, and NF-κB pathway. J Immunol 179:5483–5492

    Article  CAS  PubMed  Google Scholar 

  26. Eidet JR, Fostad IG, Shields KJ, Lyberg T, Utheim TP, Kåss A et al (2015) A Low Adiponectin Level in Rheumatoid Arthritis Is Associated with Coronary Artery Disease. Arthritis Rheumatol 67:1982–1983

    Google Scholar 

  27. Neumann E, Junker S, Schett G, Frommer K, Müller-Ladner U (2016) Adipokines in bone disease. Nat Rev Rheumatol 12:296–302

    Article  CAS  PubMed  Google Scholar 

  28. Zhang Y, Leung DY, Richers BN, Liu Y, Remigio LK, Riches DW et al (2012) Vitamin D inhibits monocyte/macrophage proinflammatory cytokine production by targeting MAPK phosphatase-1. J Immunol 1102412

  29. Sharma R, Saigal R, Goyal L, Mital P, Yadav R, Meena P et al (2014) “Estimation of vitamin D levels in rheumatoid arthritis patients and its correlation with the disease activity”. J Assoc Phys India 62:678–681

    Google Scholar 

  30. Ishikawa LLW, Colavite PM, de Campos Fraga-Silva TF, Mimura LAN, França TGD, Zorzella-Pezavento SFG et al (2017) Vitamin D deficiency and rheumatoid arthritis. Clin Rev Allergy Immunol 52:373–388

    Article  CAS  PubMed  Google Scholar 

  31. Song GG, Bae S-C, Lee YH (2012) Association between vitamin D intake and the risk of rheumatoid arthritis: a meta-analysis. Clin Rheumatol 31:1733–1739

    Article  PubMed  Google Scholar 

  32. Mateen S, Moin S, Shahzad S, Khan AQ (2017) Level of inflammatory cytokines in rheumatoid arthritis patients: Correlation with 25-hydroxy vitamin D and reactive oxygen species. PloS ONE 12:e0178879

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Lin J, Liu J, Davies ML, Chen W (2016) Serum vitamin D level and rheumatoid arthritis disease activity: review and meta-analysis. PloS ONE 11:e0146351

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Fakharan M, Haghighi A, Arabi M, Loghman M (2014) Investigating the levels of serum vitamin d in patients with rheumatoid arthritis referred to rasoul-akram hospital during 2011–2012. Iran J Med Sci 39:476

    PubMed  PubMed Central  Google Scholar 

  35. Shams E, Afshari M, Tajadini M, Keikha M, Qorbani R, Heshmat et al (2016) The relationship of serum vitamin D and Zinc in a nationally representative sample of Iranian children and adolescents: The CASPIAN-III study. Med J Islam Rep Iran 30:430

    Google Scholar 

  36. Heshmat R, Mohammad K, Majdzadeh S, Forouzanfar M, Bahrami A, Ranjbar Omrani G (2008) Vitamin D deficiency in Iran: a multi-center study among different urban areas Iran J Public Health

  37. Hajjaj-Hassouni N, Mawani N, Allali F, Rkain H, Hassouni K, Hmamouchi I et al (2017) Evaluation of vitamin D status in rheumatoid arthritis and its association with disease activity across 15 countries:“The COMORA Study”. Int J Rheumatol. https://doi.org/10.1155/2017/5491676

    Article  PubMed  PubMed Central  Google Scholar 

  38. Lee Y, Bae S-C (2016) “Vitamin D level in rheumatoid arthritis and its correlation with the disease activity: a meta-analysis”. Clin Exp Rheumatol 34:827–833

    PubMed  Google Scholar 

  39. Das BK, Panda AK, “Vitamin D (2016) The unexplored immunomodulator. Int J Rheum Dis 19:332–334

    Article  PubMed  Google Scholar 

  40. Strecker A, Mierzecki, Radomska K (2013) Copper levels in patients with rheumatoid arthritis. Ann Agric Environ Med 20:312–316

    CAS  PubMed  Google Scholar 

  41. Xin L, Yang X, Cai G, Fan D, Xia Q, Liu L et al (2015) Serum levels of copper and zinc in patients with rheumatoid arthritis: a meta-analysis. Biol Trace Elem Res 168:1–10

    Article  CAS  PubMed  Google Scholar 

  42. Zoli A, Altomonte L, Caricchio R, Galossi A, Mirone L, Ruffini M et al (1998) Serum zinc and copper in active rheumatoid arthritis: correlation with interleukin 1β and tumour necrosis factor α. Clinical Rheumatol 17:378–382

    Article  CAS  Google Scholar 

  43. Tapiero H, Tew KD (2003) Trace elements in human physiology and pathology: zinc and metallothioneins. Biomed Pharmacother 57:399–411

    Article  CAS  PubMed  Google Scholar 

  44. Ala S, Shokrzadeh M, Pur SA, Saeedi SS (2009) Zinc and copper plasma concentrations in rheumatoid arthritis patients from a selected population in Iran. Pak J Biol Sci 12:1041–1044

    Article  CAS  PubMed  Google Scholar 

  45. Söderlin M, Petersson I, Geborek P (2012) The effect of smoking on response and drug survival in rheumatoid arthritis patients treated with their first anti-TNF drug. Scand J Rheumatol 41:1–9

    Article  CAS  PubMed  Google Scholar 

  46. Chasapis CT, Loutsidou AC, Spiliopoulou CA, Stefanidou ME (2012) “Zinc and human health: an update. Arch Toxicol 86:521–534

    Article  CAS  PubMed  Google Scholar 

  47. Summersgill H, England H, Lopez-Castejon G, Lawrence C, Luheshi N, Pahle J et al (2014) Zinc depletion regulates the processing and secretion of IL-1β. Cell Death Dis 5:e1040

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Mierzecki D, Strecker, Radomska K (2011) A pilot study on zinc levels in patients with rheumatoid arthritis. Biol Trace Elem Res 143:854–862

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Miyamoto T, Katsuyama E, Kanagawa H, Fujie A, Miyamoto H, Yoshida S et al (2016) Vitamin D deficiency with high intact PTH levels is more common in younger than in older women: a study of women aged 39–64 years. Keio J Med 65:33–38

    Article  PubMed  Google Scholar 

  50. Khoshmirsafa M, Seif F, Bagheri N, Beshkar P, Mousavi M, Shirzad H (2018) Correlation of interleukin 6 and transforming growth factor β1 with peripheral blood regulatory T cells in rheumatoid arthritis patients: a potential biomarker. Cent Eur J Immunol 43(3):281

    Article  PubMed  PubMed Central  Google Scholar 

  51. Baharlou R, Atashzar MR, Vasmehjani AA, Rahimi E, Khoshmirsafa M, Seif F et al (2016) Reduced levels of T-helper 17-associated cytokines in the serum of patients with breast cancer: indicators for following the course of disease. Cent Eur J Immunol 41(1):78

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

This study was supported by a Grant of Rasoul Akram hospital. We would also appreciate the kind staff of Massoud clinical laboratory for their collaboration.

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Correspondence to Anousheh Haghighi.

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Khajoei, S., Hassaninevisi, M., Kianmehr, N. et al. Serum levels of adiponectin and vitamin D correlate with activity of Rheumatoid Arthritis. Mol Biol Rep 46, 2505–2512 (2019). https://doi.org/10.1007/s11033-019-04682-1

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