JBM  Vol.5 No.9 , September 2017
Gene Expression of Tumor Necrosis Factor-Alpha in Etanercept-Treated Rheumatoid Arthritis Patients
Abstract: Fifty-one rheumatoid arthritis (RA) patients were enrolled to assess the gene expression of tumor necrosis factor-alpha (TNF-α) by reverse transcription quantitative polymerase chain reaction (qRT-PCR) in etanercept-treated RA patients, with some emphasis on clinical and biological markers of disease. The results revealed that the ΔCt mean range in total, male and female RA patients and controls was 1.286 ± 1.226 - 4.023 ± 0.856 and the differences were not. Laboratory and clinical findings in subgroups of patients also showed no significant variations in the distribution of 2-ΔΔCt means, with the exception of anti-cyclic citrullinated peptide (ACCP) antibodies. The lowest expression was observed in moderate positive patients (1.566 ± 1.104) compared to low and high positive patients (4.061 ± 1.366 and 9.668 ± 3.518, respectively) for ACCP antibodies, and the difference was significant (p = 0.043). Inspecting the 2-ΔΔCt means in duration of disease and gender revealed that male patients recorded a lower mean than female patients (0.827 ± 0.550 vs. 4.143 ± 1.317) at <5 years disease duration, while at >10 years duration of disease, female patients showed a lower mean than male patients (1.242 ± 0.372 vs. 5.607 ± 3.334). However, both differences were not significant. It is concluded that etanercept was effective in normalizing the TNF gene expression, but variations that were related to gender, duration of disease and some biological markers of disease, were observed.
Cite this paper: Mahmood, A. , Al-Kazaz, A. , Ad’hiah, A. and Mayouf, K. (2017) Gene Expression of Tumor Necrosis Factor-Alpha in Etanercept-Treated Rheumatoid Arthritis Patients. Journal of Biosciences and Medicines, 5, 1-9. doi: 10.4236/jbm.2017.59001.

[1]   Cross, M., Smith, E., Hoy, D., Carmona, L., Wolfe, F., Vos, T., et al. (2014) The Global Burden of Rheumatoid Arthritis: Estimates from the Global Burden of Disease 2010 Study. Annals of the Rheumatic Diseases, 73, 1316-1322.

[2]   Jalil, S.F., Arshad, M., Bhatti, A., Ahmad, J., Akbar, F., Ali, S., et al. (2016) Rheumatoid Arthritis: What Have We Learned about the Causing Factors? Pakistan Journal of Pharmaceutical Sciences, 29, 629-645.

[3]   Iltchev, P., Sliwczyński, A., Czeleko, T., Sierocka, A., Tlustochowicz, M., Tlustochowicz, W., et al. (2016) Epidemiology of Rheumatoid Arthritis (RA) in Rural and Urban Areas of Poland—2008-2012. Annals of Agricultural and Environmental Medicine, 23, 350-356.

[4]   Mcinnes, I.B. and Schett, G. (2011) The Pathogenesis of Rheumatoid Arthritis. The New England Journal of Medicine, 365, 2205-2219.

[5]   Mateen, S., Zafar, A., Moin, S., Khan, A.Q. and Zubair, S. (2016) Understanding the Role of Cytokines in the Pathogenesis of Rheumatoid Arthritis. Clinica Chimica Acta, 455, 161-171.

[6]   Brzustewicz, E. and Bryl, E. (2015) The Role of Cytokines in the Pathogenesis of Rheumatoid Arthritis—Practical and Potential Application of Cytokines as Biomarkers and Targets of Personalized Therapy. Cytokine, 76, 527-536.

[7]   Levine, S.J. (2006) Tumor Necrosis Factor Alpha (TNF-α). Encyclopedia of Respiratory Medicine, Elsevier, 307-311.

[8]   Wu, H. and Hymowitz, S.G. (2009) Structure and Function of Tumor Necrosis Factor (TNF) at the Cell Surface. 2nd Edition, Handbag Cell Signal, 265-275.

[9]   Jarvis, B. and Faulds, D. (1999) Etanercept: A Review of Its Use in Rheumatoid Arthritis. Drugs, 57, 945-966.

[10]   Culy, C.R. and Keating, G.M. (2003) Spotlight on Etanercept in Rheumatoid Arthritis, Psoriatic Arthritis and Juvenile Rheumatoid Arthritis. BioDrugs, 17, 139-145.

[11]   Cuchacovich, M., Bueno, D., Carvajal, R., Bravo, N., Aguillón, J.C., Catalán, D., et al. (2014) Clinical Parameters and Biomarkers for Anti-TNF Treatment Prognosis in Rheumatoid Arthritis Patients. Clinical Rheumatology, 33, 1707-1714.

[12]   Aletaha, D., Neogi, T., Silman, A.J., Funovits, J., Felson, D.T., Iii, C.O.B., et al. (2010) Rheumatoid Arthritis Classification Criteria?: An American College of Rheumatology/European League against Rheumatism Collaborative Initiative. Annals of the Rheumatic Diseases, 69, 1580-1588.

[13]   Sengul, I., Akcay-Yalbuzdag, S., Ince, B., Goksel-Karatepe, A. and Kaya, T. (2015) Comparison of the DAS28-CRP and DAS28-ESR in Patients with Rheumatoid Arthritis. International Journal of Rheumatic Diseases, 18, 640-645.

[14]   Mariaselvam, C.M., Aoki, M., Salah, S., Boukouaci, W., Moins-Teisserenc, H., Charron, D., et al. (2014) Cytokine Expression and Cytokine-Based T Cell Profiling in South Indian Rheumatoid Arthritis. Immunobiology, 219, 772-777.

[15]   Stephenson, F.H. (2016) Chapter 9 Real-Time PCR. Calc. Mol. Biol. Biotechnol., p. 215-320.

[16]   Schwartzman, S., Fleischmann, R. and Morgan, G.J. (2004) Do Anti-TNF Agents Have Equal Efficacy in Patients with Rheumatoid Arthritis? Arthritis Research & Therapy, 6, S3-S11.

[17]   Mok, C.C., van der Kleij, D. and Wolbink, G.J. (2013) Drug Levels, Anti-Drug Antibodies, and Clinical Efficacy of the Anti-TNF? Biologics in Rheumatic Diseases. Clinical Rheumatology, 32, 1429-1435.

[18]   Yi, H., Kim, J., Jung, H., Rim, Y., Kim, Y., Jung, S., et al. (2014) Induced Production of Anti-Etanercept Antibody in Collagen-Induced Arthritis. Molecular Medicine Reports, 9, 2301-2308.

[19]   Gibellini, L., De Biasi, S., Bianchini, E., Bartolomeo, R., Fabiano, A., Manfredini, M., et al. (2016) Anti-TNF? Drugs Differently Affect the TNF sTNFR System and Monocyte Subsets in Patients with Psoriasis. PLoS ONE, 11, e0167757.

[20]   Mewar, D. and Wilson, A.G. (2011) Treatment of Rheumatoid Arthritis with Tumour Necrosis Factor Inhibitors. British Journal of Pharmacology, 162, 785-791.

[21]   Moreland, L.W., Weinblatt, M.E., Keystone, E.C., Kremer, J.M., Martin, R.W., Schiff, M.H., et al. (2006) Etanercept Treatment in Adults with Established Rheumatoid Arthritis: 7 Years of Clinical Experience. The Journal of Rheumatology, 33, 854-861.

[22]   Keystone, E., Freundlich, B., Schiff, M., Li, J. and Hooper, M. (2009) Patients with Moderate Rheumatoid Arthritis (RA) Achieve Better Disease Activity States with Etanercept Treatment than Patients with Severe RA. The Journal of Rheumatology, 36, 522-531.