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Circulating leptin level in rheumatoid arthritis and its correlation with disease activity: a meta-analysis

Zirkulierender Leptinwert bei rheumatischer Arthritis und seine Korrelation mit der Erkrankungsaktivität: eine Metaanalyse

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Abstract

Objective

This study aimed to evaluate the relationship between the circulating serum leptin level and rheumatoid arthritis (RA) and to establish a correlation between serum leptin levels and RA activity.

Methods

We searched the PUBMED, EMBASE, and Cochrane databases. A meta-analysis was performed, comparing the serum/plasma leptin levels in patients with RA and healthy controls. Correlation coefficients between serum leptin level and either disease activity score 28 (DAS28) or C‑reactive protein (CRP) in RA patients were also examined.

Results

Thirteen studies with a total of 648 RA patients and 426 controls were included in this meta-analysis. Circulating leptin level was significantly higher in the RA group than in the control group (SMD = 1.056, 95 % CI = 0.647–1.465, p = 4.2 × 10−7). In addition, stratification by ethnicity showed a significantly elevated leptin level in the RA group in Caucasian, Turkish, and Arab populations (SMD = 0.813, 95 % CI = 0.137–1.490, p = 0.018, SMD = 0.981, 95 % CI = 0.307–1.655, p = 0.004, and SMD = 1.469, 95 % CI = 0.443–2.495, p = 0.005 respectively). A meta-analysis of correlation coefficients showed a small but significantly positive correlation between the circulating leptin level and either DAS28 (correlation coefficient = 0.275, 95 % CI = 0.076–0.452, p = 0.007) or CRP (correlation coefficient = 0.274, 95 % CI = 0.068–0.458, p = 0.010).

Conclusions

Our meta-analysis demonstrated that the circulating leptin level is significantly higher in patients with RA and that a small but significantly positive correlation exists between leptin levels and RA activity.

Zusammenfassung

Ziel

Ziel der Studie war es, den Zusammenhang zwischen zirkulierendem Serumleptinspiegel und rheumatischer Arthritis (RA) zu untersuchen und eine Korrelation zwischen Serumleptinspiegeln und der RA-Aktivität festzustellen.

Methoden

Wir durchsuchten die Datenbanken PUBMED, EMBASE und Cochrane. Eine Metaanalyse wurde durchgeführt, bei der die Serum-/Plasmaleptinspiegel bei RA-Patienten und bei gesunden Kontrollgruppen untersucht wurden. Der Korrelationskoeffizient zwischen Serumleptinspiegel und entweder der Krankheitsaktivität 28 (disease activity score; DAS28) oder C‑reaktivem Protein (CRP) bei RA-Patienten wurden ebenfalls untersucht.

Ergebnisse

Dreizehn Studien mit insgesamt 648 Patienten und 426 Kontrollpersonen wurde in die Metaanalyse einbezogen. Der zirkulierende Leptinspiegel war in der RA-Gruppe signifikant höher als in der Kontrollgruppe (SMD = 1,056, 95 % CI = 0,647–1,465, p = 4,2 × 10− 7). Die Schichtung nach Ethnie zeigte einen signifikant erhöhten Leptinspiegel in der RA-Gruppe bei der hellhäutigen, türkischen und arabischen Bevölkerung (SMD = 0,813, 95 % CI = 0,137–1,490, p = 0,018, SMD = 0,981, 95 % CI = 0,307–1,655, p = 0,004 bzw. SMD = 1,469, 95 % CI = 0,443–2,495, p = 0,005). Eine Metaanalyse der Korrelationskoeffizienten zeigte eine kleine, aber signifikant positive Korrelation zwischen dem zirkulierendem Leptinspiegel und entweder DAS28 (Korrelationskoeffizient = 0,275, 95 % CI = 0,076–0,452, p = 0,007) oder CRP (Korrelationskoeffizient = 0,274, 95 % CI = 0,068–0,458, p = 0,010).

Zusammenfassung

Unsere Metaanalyse konnte darlegen, dass der zirkulierende Leptinspiegel bei Patienten mit RA signifikant höher ist und dass eine kleine aber signifikant positive Korrelation zwischen Leptinspiegeln und der RA-Aktivität besteht.

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References

  1. Harris ED Jr (1990) Rheumatoid arthritis. Pathophysiology and implications for therapy. N Engl J Med 322(18):1277–1289

    Article  PubMed  Google Scholar 

  2. Choi SJ, Rho YH, Ji JD, Song GG, Lee YH (2006) Genome scan meta-analysis of rheumatoid arthritis. Rheumatology (Oxford) 45(2):166–170

    Article  CAS  Google Scholar 

  3. Kelesidis T, Kelesidis I, Chou S, Mantzoros CS (2010) Narrative review: the role of leptin in human physiology: emerging clinical applications. Ann Intern Med 152(2):93–100

    Article  PubMed  PubMed Central  Google Scholar 

  4. Conde J, Scotece M, Gómez R, López V, Gómez-Reino JJ, Lago F et al (2011) Adipokines: biofactors from white adipose tissue. A complex hub among inflammation, metabolism, and immunity. Biofactors 37(6):413–420

    Article  CAS  PubMed  Google Scholar 

  5. Fantuzzi G, Faggioni R (2000) Leptin in the regulation of immunity, inflammation, and hematopoiesis. J Leukoc Biol 68(4):437–446

    CAS  PubMed  Google Scholar 

  6. Fernández-Riejos P, Najib S, Santos-Alvarez J, Martín-Romero C, Pérez-Pérez A, González-Yanes C et al (2010) Role of leptin in the activation of immune cells. Mediat Inflamm 2010:568343

    Article  Google Scholar 

  7. Gabay C, Dreyer M, Pellegrinelli N, Chicheportiche R, Meier CA (2001) Leptin directly induces the secretion of interleukin 1 receptor antagonist in human monocytes. J Clin Endocrinol Metab 86(2):783–791

    CAS  PubMed  Google Scholar 

  8. Li HM, Zhang TP, Leng RX, Li XP, Li XM, Pan HF (2015) Plasma/serum leptin levels in patients with systemic lupus erythematosus: a meta-analysis. Arch Med Res 46(7):551–556

    Article  CAS  PubMed  Google Scholar 

  9. Matarese G, Sanna V, Di Giacomo A, Lord GM, Howard JK, Bloom SR et al (2001) Leptin potentiates experimental autoimmune encephalomyelitis in SJL female mice and confers susceptibility to males. Eur J Immunol 31(5):1324–1332

    Article  CAS  PubMed  Google Scholar 

  10. Abdalla M, Effat D, Sheta M, Hamed WE (2014) Serum leptin levels in rheumatoid arthritis and relationship with disease activity. Egypt Rheumatol 36(1):1–5

    Article  Google Scholar 

  11. Olama SM, Senna MK, Elarman M (2012) Synovial/serum leptin ratio in rheumatoid arthritis: the association with activity and erosion. Rheumatol Int 32(3):683–690

    Article  CAS  PubMed  Google Scholar 

  12. Allam A, Radwan A (2012) The relationship of serum leptin levels with disease activity in Egyptian patients with rheumatoid arthritis. Egypt Rheumatol 34(4):185–190

    Article  CAS  Google Scholar 

  13. Ismail F, HA-h A, Ibrahim HM (2011) Possible role of leptin, and tumor necrosis factor-alpha in hypoandrogenicity in patients with early rheumatoid arthritis. Egypt Rheumatol 33(4):209–215

    Article  CAS  Google Scholar 

  14. El-Batch MM, Zakaria SS, Farouk G, El Saadany H, Selim M (2010) Changes in visfatin, adiponectin, leptin and ghrelin levels in patients with rheumatoid arthritis and their correlation with disease activity. Turkish J Biochem Biyokimya Dergisi 35(1):50–57

    CAS  Google Scholar 

  15. Seven A, Guzel S, Aslan M, Hamuryudan V (2009) Serum and synovial fluid leptin levels and markers of inflammation in rheumatoid arthritis. Rheumatol Int 29(7):743–747

    Article  CAS  PubMed  Google Scholar 

  16. Rho YH, Solus J, Sokka T, Oeser A, Chung CP, Gebretsadik T et al (2009) Adipocytokines are associated with radiographic joint damage in rheumatoid arthritis. Arthritis Rheum 60(7):1906–1914

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Turhanoğlu AD, Özmen Ş, Ogün C, Kaplan A (2009) Plasma resistin and leptin levels in overweight and lean patients with rheumatoid arthritis. Turk J Med Sci 39(3):447–451

    Google Scholar 

  18. Hizmetli S, Kisa M, Gokalp N, Bakici MZ (2007) Are plasma and synovial fluid leptin levels correlated with disease activity in rheumatoid arthritis? Rheumatol Int 27(4):335–338

    Article  CAS  PubMed  Google Scholar 

  19. Gunaydin R, Kaya T, Atay A, Olmez N, Hur A, Koseoglu M (2006) Serum leptin levels in rheumatoid arthritis and relationship with disease activity. South Med J Birm Ala 99(10):1078

    Article  Google Scholar 

  20. Otero M, Lago R, Gomez R, Lago F, Dieguez C, Gomez-Reino JJ et al (2006) Changes in plasma levels of fat-derived hormones adiponectin, leptin, resistin and visfatin in patients with rheumatoid arthritis. Ann Rheum Dis 65(9):1198–1201

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Popa C, Netea MG, Radstake TR, van Riel PL, Barrera P, van der Meer JW (2005) Markers of inflammation are negatively correlated with serum leptin in rheumatoid arthritis. Ann Rheum Dis 64(8):1195–1198

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Bokarewa M, Bokarew D, Hultgren O, Tarkowski A (2003) Leptin consumption in the inflamed joints of patients with rheumatoid arthritis. Ann Rheum Dis 62(10):952–956

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Lee YH, Woo JH, Choi SJ, Ji JD, Song GG (2010) Associations between osteoprotegerin polymorphisms and bone mineral density: a meta-analysis. Mol Biol Rep 37(1):227–234

    Article  CAS  PubMed  Google Scholar 

  24. Lee YH, Rho YH, Choi SJ, Ji JD, Song GG (2007) PADI4 polymorphisms and rheumatoid arthritis susceptibility: a meta-analysis. Rheumatol Int 27(9):827–833

    Article  CAS  PubMed  Google Scholar 

  25. Lee YH, Woo JH, Choi SJ, Ji JD, Song GG (2010) Induction and maintenance therapy for lupus nephritis: a systematic review and meta-analysis. Lupus 19(6):703–710

    Article  CAS  PubMed  Google Scholar 

  26. Hozo SP, Djulbegovic B, Hozo I (2005) Estimating the mean and variance from the median, range, and the size of a sample. BMC Med Res Methodol 5:13

    Article  PubMed  PubMed Central  Google Scholar 

  27. Wells GA, Shea B, O’Connell D, Peterson J, Welch V, Losos M et al (2011) The Newcastle-Ottawa Scale (NOS) for assessing the quality of nonrandomised studies in meta-analyses. Ottawa Health Research Institute, Ottawa. http://www.ohri.ca/programs/clinical_epidemiology/oxford.htm

    Google Scholar 

  28. Egger M, Smith GD, Phillips AN (1997) Meta-analysis: principles and procedures. BMJ 315(7121):1533–1537

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. DerSimonian R, Laird N (1986) Meta-analysis in clinical trials. Control Clin Trials 7(3):177–188

    Article  CAS  PubMed  Google Scholar 

  30. Higgins JP, Thompson SG (2002) Quantifying heterogeneity in a meta-analysis. Stat Med 21(11):1539–1558

    Article  PubMed  Google Scholar 

  31. Egger M, Davey Smith G, Schneider M, Minder C (1997) Bias in meta-analysis detected by a simple, graphical test. BMJ 315(7109):629–634

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Aminzadeh MA, Pahl MV, Barton CH, Doctor NS, Vaziri ND (2009) Human uraemic plasma stimulates release of leptin and uptake of tumour necrosis factor-alpha in visceral adipocytes. Nephrol Dial Transplant 24(12):3626–3631

    Article  CAS  PubMed  Google Scholar 

  33. Gunaydin R, Kaya T, Atay A, Olmez N, Hur A, Koseoglu M (2006) Serum leptin levels in rheumatoid arthritis and relationship with disease activity. South Med J 99(10):1078–1083

    Article  PubMed  Google Scholar 

  34. Otero M, Lago R, Gomez R, Dieguez C, Lago F, Gómez-Reino J et al (2006) Towards a pro-inflammatory and immunomodulatory emerging role of leptin. Rheumatology 45(8):944–950

    Article  CAS  PubMed  Google Scholar 

  35. Iikuni N, Lam QL, Lu L, Matarese G, La Cava A (2008) Leptin and Inflammation. Curr Immunol Rev 4(2):70–79

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Lord GM, Matarese G, Howard JK, Baker RJ, Bloom SR, Lechler RI (1998) Leptin modulates the T-cell immune response and reverses starvation-induced immunosuppression. Nature 394(6696):897–901

    Article  CAS  PubMed  Google Scholar 

  37. White DW, Kuropatwinski KK, Devos R, Baumann H, Tartaglia LA (1997) Leptin receptor (OB-R) signaling. Cytoplasmic domain mutational analysis and evidence for receptor homo-oligomerization. J Biol Chem 272(7):4065–4071

    Article  CAS  PubMed  Google Scholar 

  38. Muraoka S, Kusunoki N, Takahashi H, Tsuchiya K, Kawai S (2013) Leptin stimulates interleukin-6 production via janus kinase 2/signal transducer and activator of transcription 3 in rheumatoid synovial fibroblasts. Clin Exp Rheumatol 31(4):589–595

    PubMed  Google Scholar 

  39. Alshaker H, Wang Q, Frampton AE, Krell J, Waxman J, Winkler M et al (2015) Sphingosine kinase 1 contributes to leptin-induced STAT3 phosphorylation through IL-6/gp130 transactivation in oestrogen receptor-negative breast cancer. Breast Cancer Res Treat 149(1):59–67

    Article  CAS  PubMed  Google Scholar 

  40. Tian G, Liang JN, Wang ZY, Zhou D (2014) Emerging role of leptin in rheumatoid arthritis. Clin Exp Immunol 177(3):557–570

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Fazeli M, Zarkesh-Esfahani H, Wu Z, Maamra M, Bidlingmaier M, Pockley AG et al (2006) Identification of a monoclonal antibody against the leptin receptor that acts as an antagonist and blocks human monocyte and T cell activation. J Immunol Methods 312(1–2):190–200

    Article  CAS  PubMed  Google Scholar 

  42. Iliopoulos D, Malizos KN, Tsezou A (2007) Epigenetic regulation of leptin affects MMP-13 expression in osteoarthritic chondrocytes: possible molecular target for osteoarthritis therapeutic intervention. Ann Rheum Dis 66(12):1616–1621

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Feng GS (2006) Shp2 as a therapeutic target for leptin resistance and obesity. Expert Opin Ther Targets 10(1):135–142

    Article  CAS  PubMed  Google Scholar 

  44. Soebiyanto RP, Sreenath SN, Qu CK, Loparo KA, Bunting KD (2007) Complex systems biology approach to understanding coordination of JAK-STAT signaling. Biosystems 90(3):830–842

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Toussirot É, Michel F, Binda D, Dumoulin G (2015) The role of leptin in the pathophysiology of rheumatoid arthritis. Life Sci 140:29–36

    Article  CAS  PubMed  Google Scholar 

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Acknowledegment

This study was supported in part by a grant from the Korea Healthcare technology R&D Project, Ministry for Health and Welfare, Republic of Korea (HI13C2124).

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Authors and Affiliations

  1. Division of Rheumatology, Department of Internal Medicine, Korea University Anam Hospital, Korea University College of Medicine, 73, Inchon-ro, Seongbuk-gu, 136-705, Seoul, Korea

    Y. H. Lee

  2. Department of Rheumatology, Hanyang University Hospital for Rheumatic Diseases, Seoul, Korea

    S.‑C. Bae

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Correspondence to Y. H. Lee.

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Y. H. Lee and S.-C. Bae states that there are no conflicts of interest.

The accompanying manuscript does not include studies on humans or animals.

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U. Müller-Ladner, Bad Nauheim

U. Lange, Bad Nauheim

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Lee, Y.H., Bae, S. Circulating leptin level in rheumatoid arthritis and its correlation with disease activity: a meta-analysis. Z Rheumatol 75, 1021–1027 (2016). https://doi.org/10.1007/s00393-016-0050-1

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  • DOI: https://doi.org/10.1007/s00393-016-0050-1

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