Skip to main content

Advertisement

SpringerLink
Log in

Effects of Tumor Necrosis Factor Inhibitor on Serum Level of HLA-B27 and PDCD-1 in Patients with Ankylosing Spondylitis

  • Original Paper
  • Published:
Cell Biochemistry and Biophysics Aims and scope Submit manuscript

Abstract

The aim of this study was to evaluate the effect of tumor necrosis factor-alpha (TNF-α) inhibitor-infliximab on ankylosing spondylitis (AS) patients and detect the serum level of HLA-B27 and PDCD-1 before and after TNF inhibitor treatment. 138 patients at active stage of AS were treated with infliximab; serum was collected before and after TNF-α inhibitor treatment for analysis. Reverse transcription-polymerase chain reaction (RT-PCR), flow cytometry, and enzyme-linked immuno sorbent assay were applied to detect the levels of HLA-B27 and PDCD-1 at different time points, which were used for statistical analysis with clinical data including two AS indicators (erythrocyte sedimentation rate—ESR and C-reactive protein—CRP). After the treatment for 6 weeks, RT-PCR showed that the gene expressions of HLA-B27 and PDCD-1 were significantly downregulated compared with baseline before infliximab treatment (P < 0.05); flow cytometry showed that the HLA-B27 and PDCD-1 double-labeled cells were significantly downregulated (P < 0.05). After 2, 6, or 10 weeks of infliximab treatment, the levels of ESR, CRP, serum HLA-B27, and PDCD-1 of the AS patients were all significantly lower than the baseline levels (P < 0.05), and the serum HLA-B27 and PDCD-1 levels were all significantly correlated with ESR (P < 0.05). Infliximab, an anti-TNF-α inhibitor, decreases significantly not only ESR and CRP, but also the serum levels of HLA-B27 and PDCD-1 in patients with AS. HLA-B27 and PDCD-1 are involved in the pathogenesis, and disease activities of AS. HLA-B27 and PDCD-1 are potentially the useful markers of AS activity and useful parameters to evaluate the effectiveness of anti-TNF-α inhibitor in treating AS.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Zink, A., Braun, J., Listing, J., & Wollenhaupt, J. (2000). Disability and handicap in rheumatoid arthritis and ankylosing spondylitis-results from the German rheumatological database. German Collaborative Arthritis Centers. The Journal of Rheumatology, 27(3), 613–622.

    PubMed  CAS  Google Scholar 

  2. Rostamian, A., Mazoochy, H., Movassaghi, S., Mortazavi, S. M., Sadeghzadeh, E., Shahbazi, F., et al. (2014). Coexistence of ankylosing spondylitis and hereditary multiple exostoses: Coincidence or association. Iranian Journal of Radiology, 11(1), e4242.

    PubMed  PubMed Central  Google Scholar 

  3. Tekatas, A., & Pamuk, O. N. (2014). Increased frequency of restless leg syndrome in patients with ankylosing spondylitis. International Journal of Rheumatic Diseases,. doi:10.1111/1756-185X.12323.

    PubMed  Google Scholar 

  4. Braun, J., Bollow, M., Remlinger, G., Eggens, U., Rudwaleit, M., Distler, A., et al. (1998). Prevalence of spondylarthropathies in HLA-B27 positive and negative blood donors. Arthritis and Rheumatism, 41(1), 58–67.

    Article  PubMed  CAS  Google Scholar 

  5. Zink, A., Listing, J., Klindworth, C., & Zeidler, H. (2001). The national database of the German Collaborative Arthritis Centres: I. Structure, aims, and patients. Annals of the Rheumatic Diseases, 60(3), 199–206.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  6. Yang, P. T., Xiao, W. G., Qin, L., Zhao, L. J., He, L. M., & Ito, M. (2010). A pilot study on changes of macrophage colony stimulating factor and transforming growth factor beta1 in male patients with ankylosing spondylitis taking thalidomide. Annals of the Rheumatic Diseases, 69(4), 781–782.

    Article  PubMed  CAS  Google Scholar 

  7. Maksymowych, W. P. (2007). Update on the treatment of ankylosing spondylitis. Therapeutics and Clinical Risk Management, 3(6), 1125–1133.

    PubMed  CAS  PubMed Central  Google Scholar 

  8. Feng XH, Jiang Q, Liu HX, Wang HL, He XX, Zhang HD, Tang XP, Xu FQ, Liu J, Zhou CY et al [Clinical effect analysis of ankylosing spondylitis treated by Chinese medical syndrome differentiation]. Zhongguo Zhong xi yi jie he za zhi Zhongguo Zhongxiyi jiehe zazhi = Chinese Journal of Integrated Traditional and Western Medicine/Zhongguo Zhong xi yi jie he xue hui, Zhongguo Zhong yi yan jiu yuan zhu ban 2013, 33(10):1309–1314.

  9. Zochling, J., & Braun, J. (2005). Management and treatment of ankylosing spondylitis. Current Opinion in Rheumatology, 17(4), 418–425.

    Article  PubMed  CAS  Google Scholar 

  10. Kiltz, U., Sieper, J., & Braun, J. (2013). ASAS/EULAR recommendations for the management of ankylosing spondylitis: Evaluation of the 2010 update in the German-speaking area. Zeitschrift fur Rheumatologie, 72(1), 71–80.

    Article  PubMed  CAS  Google Scholar 

  11. Sampaio-Barros, P. D., Keiserman, M., Meirelles Ede, S., Pinheiro Mde, M., Ximenes, A. C., Azevedo, V. F., et al. (2013). Recommendations for the management and treatment of ankylosing spondylitis. Revista Brasileira de Reumatologia, 53(3), 242–257.

    Article  PubMed  Google Scholar 

  12. Can, M., Aydin, S. Z., Nigdelioglu, A., Atagunduz, P., & Direskeneli, H. (2012). Conventional DMARD therapy (methotrexate–sulphasalazine) may decrease the requirement of biologics in routine practice of ankylosing spondylitis patients: A real-life experience. International Journal of Rheumatic Diseases, 15(6), 526–530.

    Article  PubMed  CAS  Google Scholar 

  13. Miranda-Filloy, J. A., Llorca, J., Carnero-Lopez, B., Gonzalez-Juanatey, C., Blanco, R., & Gonzalez-Gay, M. A. (2012). TNF-alpha antagonist therapy improves insulin sensitivity in non-diabetic ankylosing spondylitis patients. Clinical and Experimental Rheumatology, 30(6), 850–855.

    PubMed  Google Scholar 

  14. Voloshyna, I., Seshadri, S., Anwar, K., Littlefield, M. J., Belilos, E., Carsons, S. E., et al. (2014). Infliximab reverses suppression of cholesterol efflux proteins by TNF-alpha: A possible mechanism for modulation of atherogenesis. BioMed Research International, 2014, 312647.

    Article  PubMed  PubMed Central  Google Scholar 

  15. Furst, D. E., Keystone, E. C., So, A. K., Braun, J., Breedveld, F. C., Burmester, G. R., et al. (2013). Updated consensus statement on biological agents for the treatment of rheumatic diseases, 2012. Annals of the Rheumatic Diseases, 72(Suppl 2), ii2–34.

    PubMed  CAS  Google Scholar 

  16. Braun, J., & Sieper, J. (2004). Biological therapies in the spondyloarthritis: the current state. Rheumatology (Oxford), 43(9), 1072–1084.

    Article  CAS  Google Scholar 

  17. Braun, J., Deodhar, A., Dijkmans, B., Geusens, P., Sieper, J., Williamson, P., et al. (2008). Efficacy and safety of infliximab in patients with ankylosing spondylitis over a two-year period. Arthritis and Rheumatism, 59(9), 1270–1278.

    Article  PubMed  CAS  Google Scholar 

  18. Evans, D. M., Spencer, C. C., Pointon, J. J., Su, Z., Harvey, D., Kochan, G., et al. (2011). Interaction between ERAP1 and HLA-B27 in ankylosing spondylitis implicates peptide handling in the mechanism for HLA-B27 in disease susceptibility. Nature Genetics, 43(8), 761–767.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  19. Li, M. Y., Yao, Z. Q., & Liu, X. Y. (2011). Advance of research on HLA-B27 and the immunological mechanism of ankylosing spondylitis. Sheng li ke xue jin zhan [Progress in Physiology], 42(1), 16–20.

    Google Scholar 

  20. Gu, X., Wu, H., & Fu, P. (2013). Allicin attenuates inflammation and suppresses HLA-B27 protein expression in ankylosing spondylitis mice. BioMed Research International, 2013, 171573.

    PubMed  PubMed Central  Google Scholar 

  21. Wu, Z., Mou, Y., Lin, Z., Huang, J., Wei, Q., & Gu, J. (2009). HLA-B27 polymorphism in Han Chinese patients with ankylosing spondylitis: A distinctive disease association for B*2715 in a multiplex family. The Journal of Rheumatology, 36(12), 2849–2850.

    Article  PubMed  Google Scholar 

  22. Brewerton, D. A., Hart, F. D., Nicholls, A., Caffrey, M., James, D. C., & Sturrock, R. D. (1973). Ankylosing spondylitis and HL-A 27. Lancet, 1(7809), 904–907.

    Article  PubMed  CAS  Google Scholar 

  23. Diyarbakir, E., Eyerci, N., Melikoglu, M., Topcu, A., & Pirim, I. (2012). HLA B27 subtype distribution among patients with ankylosing spondylitis in eastern Turkey. Genetic Testing and Molecular Biomarkers, 16(5), 456–458.

    Article  PubMed  CAS  Google Scholar 

  24. Mahmoudi, M., Amirzargar, A. A., Jamshidi, A. R., Farhadi, E., Noori, S., Avraee, M., et al. (2011). Association of IL1R polymorphism with HLA-B27 positive in Iranian patients with ankylosing spondylitis. European Cytokine Network, 22(4), 175–180.

    PubMed  CAS  Google Scholar 

  25. Peng, W., Liu, C., Xu, C., Lou, Y., Chen, J., Yang, Y., et al. (2012). PD-1 blockade enhances T-cell migration to tumors by elevating IFN-gamma inducible chemokines. Cancer Research, 72(20), 5209–5218.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  26. Tahoori, M. T., Pourfathollah, A. A., Akhlaghi, M., Daneshmandi, S., Nicknam, M. H., & Soleimanifar, N. (2011). Association of programmed cell death-1 (PDCD-1) gene polymorphisms with rheumatoid arthritis in Iranian patients. Clinical and Experimental Rheumatology, 29(5), 763–767.

    PubMed  Google Scholar 

  27. Hiromine, Y., Ikegami, H., Fujisawa, T., Kawabata, Y., Noso, S., Yamaji, K., et al. (2006). Molecular scanning of the gene for programmed cell death-1 (PDCD-1) as a candidate for type 1 diabetes susceptibility. Annals of the New York Academy of Sciences, 1079, 285–288.

    Article  PubMed  CAS  Google Scholar 

  28. Wei, J. C., Hung, K. S., Hsu, Y. W., Wong, R. H., Huang, C. H., Jan, M. S., et al. (2012). Genetic polymorphisms of stromal interaction molecule 1 associated with the erythrocyte sedimentation rate and C-reactive protein in HLA-B27 positive ankylosing spondylitis patients. PLoS ONE, 7(12), e49698.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  29. de Vries, M. K., van Eijk, I. C., van der Horst-Bruinsma, I. E., Peters, M. J., Nurmohamed, M. T., Dijkmans, B. A., et al. (2009). Erythrocyte sedimentation rate, C-reactive protein level, and serum amyloid a protein for patient selection and monitoring of anti-tumor necrosis factor treatment in ankylosing spondylitis. Arthritis and Rheumatism, 61(11), 1484–1490.

    Article  PubMed  Google Scholar 

  30. Poddubnyy, D. A., Rudwaleit, M., Listing, J., Braun, J., & Sieper, J. (2010). Comparison of a high sensitivity and standard C reactive protein measurement in patients with ankylosing spondylitis and non-radiographic axial spondyloarthritis. Annals of the Rheumatic Diseases, 69(7), 1338–1341.

    Article  PubMed  CAS  Google Scholar 

  31. Benhamou, M., Gossec, L., & Dougados, M. (2010). Clinical relevance of C-reactive protein in ankylosing spondylitis and evaluation of the NSAIDs/coxibs’ treatment effect on C-reactive protein. Rheumatology (Oxford), 49(3), 536–541.

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Orthopaedics, The Second People’s Hospital of Huaian, Jiangsu, 223002, China

    Xiaogang Chen, Xiaoqing Zhou, Xia Li, Jinshan Tang, Xiaowu Hu & Junsheng Wang

  2. Department of Rheumatology, The Second People’s Hospital of Huaian, Jiangsu, 223002, China

    Cheng Xu

Authors
  1. Xiaogang Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Xiaoqing Zhou
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Xia Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Jinshan Tang
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Xiaowu Hu
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Junsheng Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Cheng Xu
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Xiaogang Chen.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Chen, X., Zhou, X., Li, X. et al. Effects of Tumor Necrosis Factor Inhibitor on Serum Level of HLA-B27 and PDCD-1 in Patients with Ankylosing Spondylitis. Cell Biochem Biophys 70, 1453–1457 (2014). https://doi.org/10.1007/s12013-014-0082-6

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12013-014-0082-6

Keywords

Search

Navigation