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.
Similar content being viewed by others
References
Low TL, Goldstein AL (1982) Chemical characterization of thymosin beta 4. J Biol Chem 257:1000–1006
Low TL, Goldstein AL (1985) Thymosin beta 4. Methods Enzymol 116:248–255
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
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
Philp D, Goldstein AL, Kleinman HK (2004) Thymosin beta4 promotes angiogenesis, wound healing, and hair follicle development. Mech Ageing Dev 125(2):113–115
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
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
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
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
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
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
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
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
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
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
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
Fries JF, Spitz P, Kraines RG, Holman HR (1980) Measurement of patient outcome in arthritis. Arthritis Rheum 23(2):137–145
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
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
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
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
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
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
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
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
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
Corresponding author
Rights 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
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10067-012-2011-7