Skip to main content

Advertisement

Log in

Association between serum thymosin β4 levels of rheumatoid arthritis patients and disease activity and response to therapy

  • Brief Report
  • Published:
Clinical Rheumatology Aims and scope Submit manuscript

Abstract

The aim of this study was to evaluate whether thymosin β4 (Tβ4) levels are increased in the serum of rheumatoid arthritis (RA) patients, and if this increase is associated with RA disease activity and resistance to treatment. Blood samples from 40 patients with RA were collected at baseline and 6 months after starting treatment with disease-modifying antirheumatic drugs (DMARD) and/or tumor necrosis factor (TNF)-α blocker. Serum levels of Tβ4 were measured by ELISA. Tβ4 levels (mean ± standard deviation) in RA patients were significantly (approximately tenfold) higher than in healthy controls (577.4 ± 67.92 vs. 56.61 ± 5.72 ng/mL). Serum Tβ4 levels in patients with severe disease activity before therapy were slightly higher than in patients with moderate disease activity (662.4 ± 491.5 vs. 462.5 ± 305.3 ng/ml, P > 0.05). Tβ4 levels were significantly associated with disease activity according to the 28-joint Disease Activity Score. The mean Tβ4 level at baseline in the DMARD treatment group was significantly lower than in the DMARD + TNF-α blocker treatment group. Tβ4 levels were increased in the serum of patients with RA and were positively associated with disease activity. Levels of Tβ4 may also be relevant in determining or predicting resistance to RA treatment. Further studies are necessary to determine if Tβ4 is an appropriate therapeutic target for controlling inflammation associated with RA.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Low TL, Goldstein AL (1982) Chemical characterization of thymosin beta 4. J Biol Chem 257:1000–1006

    PubMed  CAS  Google Scholar 

  2. Low TL, Goldstein AL (1985) Thymosin beta 4. Methods Enzymol 116:248–255

    Article  PubMed  CAS  Google Scholar 

  3. Crockford D, Turjman N, Allan C, Angel J (2010) Thymosin beta4: structure, function, and biological properties supporting current and future clinical applications. Ann N Y Acad Sci 1194:179–189

    Article  PubMed  CAS  Google Scholar 

  4. Grant DS, Rose W, Yaen C, Goldstein A, Martinez J, Kleinman H (1999) Thymosin beta4 enhances endothelial cell differentiation and angiogenesis. Angiogenesis 3(2):125–135

    Article  PubMed  CAS  Google Scholar 

  5. Philp D, Goldstein AL, Kleinman HK (2004) Thymosin beta4 promotes angiogenesis, wound healing, and hair follicle development. Mech Ageing Dev 125(2):113–115

    Article  PubMed  CAS  Google Scholar 

  6. Philp D, St-Surin S, Cha HJ, Moon HS, Kleinman HK, Elkin M (2007) Thymosin beta 4 induces hair growth via stem cell migration and differentiation. Ann N Y Acad Sci 1112:95–103

    Article  PubMed  CAS  Google Scholar 

  7. Iguchi K, Usami Y, Hirano K, Hamatake M, Shibata M, Ishida R (1999) Decreased thymosin beta4 in apoptosis induced by a variety of antitumor drugs. Biochem Pharmacol 57(10):1105–1111

    Article  PubMed  CAS  Google Scholar 

  8. Niu M, Nachmias VT (2000) Increased resistance to apoptosis in cells overexpressing thymosin beta four: a role for focal adhesion kinase pp 125FAK. Cell Adhes Commun 7(4):311–320

    Article  PubMed  CAS  Google Scholar 

  9. Moon EY, Im YS, Ryu YK, Kang JH (2010) Actin-sequestering protein, thymosin beta-4, is a novel hypoxia responsive regulator. Clin Exp Metastasis 27(8):601–609

    Article  PubMed  CAS  Google Scholar 

  10. Philp D, Scheremeta B, Sibliss K, Zhou M, Fine EL, Nguyen M, Wahl L, Hoffman MP, Kleinman HK (2006) Thymosin beta4 promotes matrix metalloproteinase expression during wound repair. J Cell Physiol 208(1):195–200

    Article  PubMed  CAS  Google Scholar 

  11. Kobayashi T, Okada F, Fujii N, Tomita N, Ito S, Tazawa H, Aoyama T, Choi SK, Shibata T, Fujita H et al (2002) Thymosin-beta4 regulates motility and metastasis of malignant mouse fibrosarcoma cells. Am J Pathol 160(3):869–882

    Article  PubMed  CAS  Google Scholar 

  12. Blain EJ, Mason DJ, Duance VC (2002) The effect of thymosin beta4 on articular cartilage chondrocyte matrix metalloproteinase expression. Biochem Soc Trans 30(Pt 6):879–882

    PubMed  CAS  Google Scholar 

  13. Golsteyn EJ, Fritzler MJ (1987) The role of the thymus–hypothalamus–pituitary–gonadal axis in normal immune processes and autoimmunity. J Rheumatol 14(5):982–990

    PubMed  CAS  Google Scholar 

  14. Choi HM, Lee YA, Yang HI, Yoo MC, Kim KS (2011) Increased levels of thymosin beta4 in synovial fluid of patients with rheumatoid arthritis: association of thymosin beta4 with other factors that are involved in inflammation and bone erosion in joints. Int J Rheum Dis 14(4):320–324

    Article  PubMed  Google Scholar 

  15. Arnett FC, Edworthy SM, Bloch DA, McShane DJ, Fries JF, Cooper NS, Healey LA, Kaplan SR, Liang MH, Luthra HS et al (1988) The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis. Arthritis Rheum 31(3):315–324

    Article  PubMed  CAS  Google Scholar 

  16. Inoue E, Yamanaka H, Hara M, Tomatsu T, Kamatani N (2007) Comparison of Disease Activity Score (DAS)28- erythrocyte sedimentation rate and DAS28- C-reactive protein threshold values. Ann Rheum Dis 66(3):407–409

    Article  PubMed  CAS  Google Scholar 

  17. Fries JF, Spitz P, Kraines RG, Holman HR (1980) Measurement of patient outcome in arthritis. Arthritis Rheum 23(2):137–145

    Article  PubMed  CAS  Google Scholar 

  18. Felson DT, Anderson JJ, Boers M, Bombardier C, Furst D, Goldsmith C, Katz LM, Lightfoot R Jr, Paulus H, Strand V et al (1995) American College of Rheumatology. Preliminary definition of improvement in rheumatoid arthritis. Arthritis Rheum 38(6):727–735

    Article  PubMed  CAS  Google Scholar 

  19. Badamchian M, Fagarasan MO, Danner RL, Suffredini AF, Damavandy H, Goldstein AL (2003) Thymosin beta(4) reduces lethality and down-regulates inflammatory mediators in endotoxin-induced septic shock. Int Immunopharmacol 3(8):1225–1233

    Article  PubMed  CAS  Google Scholar 

  20. Girardi M, Sherling MA, Filler RB, Shires J, Theodoridis E, Hayday AC, Tigelaar RE (2003) Anti-inflammatory effects in the skin of thymosin-beta4 splice-variants. Immunology 109(1):1–7

    Article  PubMed  Google Scholar 

  21. Sosne G, Qiu P, Christopherson PL, Wheater MK (2007) Thymosin beta 4 suppression of corneal NFkappaB: a potential anti-inflammatory pathway. Exp Eye Res 84(4):663–669

    Article  PubMed  CAS  Google Scholar 

  22. Sosne G, Szliter EA, Barrett R, Kernacki KA, Kleinman H, Hazlett LD (2002) Thymosin beta 4 promotes corneal wound healing and decreases inflammation in vivo following alkali injury. Exp Eye Res 74(2):293–299

    Article  PubMed  CAS  Google Scholar 

  23. Qiu P, Wheater MK, Qiu Y, Sosne G (2011) Thymosin beta4 inhibits TNF-alpha-induced NF-kappaB activation, IL-8 expression, and the sensitizing effects by its partners PINCH-1 and ILK. FASEB J 25(6):1815–1826

    Article  PubMed  CAS  Google Scholar 

  24. Zhang Y, Feurino LW, Zhai Q, Wang H, Fisher WE, Chen C, Yao Q, Li M (2008) Thymosin Beta 4 is overexpressed in human pancreatic cancer cells and stimulates proinflammatory cytokine secretion and JNK activation. Cancer Biol Ther 7(3):419–423

    Article  PubMed  CAS  Google Scholar 

  25. Goldstein AL, Hannappel E, Sosne G, Kleinman HK (2012) Thymosin β4: a multi-functional regenerative peptide. Basic properties and clinical applications. Expert Opin Biol Ther 12(1):37–51

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

This research was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology (2011-0009061).

Disclosures

None.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Kyoung Soo Kim.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Song, R., Choi, H.M., Yang, HI. et al. Association between serum thymosin β4 levels of rheumatoid arthritis patients and disease activity and response to therapy. Clin Rheumatol 31, 1253–1258 (2012). https://doi.org/10.1007/s10067-012-2011-7

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10067-012-2011-7

Keywords

Navigation