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. 2017 Apr 24;8(4):127.
doi: 10.3390/genes8040127.

Gene Expression Analysis before and after Treatment with Adalimumab in Patients with Ankylosing Spondylitis Identifies Molecular Pathways Associated with Response to Therapy

Marzia Dolcino  1 , Elisa Tinazzi  2 , Andrea Pelosi  3 , Giuseppe Patuzzo  4 , Francesca Moretta  5 , Claudio Lunardi  6 , Antonio Puccetti  7
Affiliations

Gene Expression Analysis before and after Treatment with Adalimumab in Patients with Ankylosing Spondylitis Identifies Molecular Pathways Associated with Response to Therapy

Marzia Dolcino et al. Genes (Basel). .

Abstract

The etiology of Ankylosing spondylitis (AS) is still unknown and the identification of the involved molecular pathogenetic pathways is a current challenge in the study of the disease. Adalimumab (ADA), an anti-tumor necrosis factor (TNF)-alpha agent, is used in the treatment of AS. We aimed at identifying pathogenetic pathways modified by ADA in patients with a good response to the treatment. Gene expression analysis of Peripheral Blood Cells (PBC) from six responders and four not responder patients was performed before and after treatment. Differentially expressed genes (DEGs) were submitted to functional enrichment analysis and network analysis, followed by modules selection. Most of the DEGs were involved in signaling pathways and in immune response. We identified three modules that were mostly impacted by ADA therapy and included genes involved in mitogen activated protein (MAP) kinase, wingless related integration site (Wnt), fibroblast growth factor (FGF) receptor, and Toll-like receptor (TCR) signaling. A separate analysis showed that a higher percentage of DEGs was modified by ADA in responders (44%) compared to non-responders (12%). Moreover, only in the responder group, TNF, Wnt, TLRs and type I interferon signaling were corrected by the treatment. We hypothesize that these pathways are strongly associated to AS pathogenesis and that they might be considered as possible targets of new drugs in the treatment of AS.

Keywords: Adalimumab (ADA); Ankylosing spondylitis; gene module; gene-array; protein-protein interaction (PPI) network.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Real time (RT)-PCR of some modulated genes in AS patients. Genes selected for validation were IL6ST, TNFRSF25, TNFSF8 and STAT1. The transcripts of the selected genes were increased in AS samples when compared to healthy donors. Relative expression levels were calculated for each sample after normalization against the housekeeping gene GAPDH. Experiments have been conducted in triplicates. Similar results were obtained using the housekeeping genes18s rRNA and beta-actin.
Figure 2
Figure 2
Network analysis of differentially expressed genes (DEGs) in AS patients. (A) Protein-protein interaction (PPI) network of DEGs; (B) Degree Sorted Circle Layout of the PPI network. Nodes are ordered around a circle based on their degree of connectivity (number of edges). Nodes belonging to modules are highlighted in red; (C) Modules originated from the interaction network.
Figure 3
Figure 3
Protein-protein interaction (PPI) network of DEGs in AS patients after treatment.
See this image and copyright information in PMC

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References

    1. Stolwijk C., Essers I., van Tubergen A., Boonen A., Bazelier M.T., de Bruin M.L., de Vries F. The epidemiology of extra-articular manifestations in ankylosing spondylitis: A population-based matched cohort study. Ann. Rheum. Dis. 2015;74:1373–1378. doi: 10.1136/annrheumdis-2014-205253. - DOI - PubMed
    1. Reveille J.D. An update on the contribution of the MHC to as susceptibility. Clin. Rheumatol. 2014;33:749–757. doi: 10.1007/s10067-014-2662-7. - DOI - PMC - PubMed
    1. Braun J., van den Berg R., Baraliakos X., Boehm H., Burgos-Vargas R., Collantes-Estevez E., Dagfinrud H., Dijkmans B., Dougados M., Emery P., et al. 2010 update of the ASAS/EULAR recommendations for the management of ankylosing spondylitis. Ann. Rheum. Dis. 2011;70:896–904. doi: 10.1136/ard.2011.151027. - DOI - PMC - PubMed
    1. Ward M.M., Deodhar A., Akl E.A., Lui A., Ermann J., Gensler L.S., Smith J.A., Borenstein D., Hiratzka J., Weiss P.F., et al. American college of rheumatology/spondylitis association of america/spondyloarthritis research and treatment network 2015 recommendations for the treatment of ankylosing spondylitis and nonradiographic axial spondyloarthritis. Arthritis Rheumatol. 2016;68:282–298. doi: 10.1002/art.39298. - DOI - PMC - PubMed
    1. Sieper J., oddubnyy D. New evidence on the management of spondyloarthritis. Nat. Rev. Rheumatol. 2016;12:282–295. doi: 10.1038/nrrheum.2016.42. - DOI - PubMed

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