Skip to main content

Advertisement

Log in

Distinct genetic profile in peripheral blood mononuclear cells of psoriatic arthritis patients treated with methotrexate and TNF-inhibitors

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

Abstract

Psoriatic arthritis (PsA) is a systemic inflammatory condition associated with psoriasis. Despite considerable heterogeneity in clinical presentation, genetic studies and animal models support the notion that PsA is a distinct disease. We aimed to characterize the PsA genotype by gene expression profile and to research the effect in gene modulation of methotrexate (MTX) and TNF-inhibitors (TNF-I) in PsA-treated patients. Nine PsA patients, according to CASPAR criteria, and three healthy controls were recruited from an outpatient rheumatology clinic. Three out of nine PsA patients were naïve to treatment, three received TNF-I, and the remaining three were on MTX-monotherapy. Blood samples were collected and analyzed by human genome U95 Array-Affymetrix (GeneChip® instrument system). Identification of statistically significant differences between differentially expressed genes was determined by Mann–Whitney and t test (p < 0.05). The microarray profile identified a predominance of differentially expressed genes with an increased expression in baseline PsA patients: 115/12,000 genes were up-regulated and 13/12,000 down-regulated, as compared to healthy controls. The great majority were involved in inflammatory cells and pathways. In the biologic-treated patients, a higher number of down-regulated genes were expressed vs. the MTX patients, 161 vs. 33, respectively. This study shows that in PsA patients, TNF-I and MTX are able to modulate the gene expression in a synergistic and additive manner.

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

Similar content being viewed by others

Abbreviations

PsA:

Psoriatic arthritis

Ps:

Psoriasis

MTX:

Methotrexate, TNF-α, tumor necrosis factor-α

SLE:

Systemic lupus erythematosus

RA:

Rheumatoid arthritis

AS:

Ankylosing spondylitis

PBMCs:

Peripheral blood mononuclear cells

DNA:

Deoxyribonucleic acid

DEG:

Differentially expressed genes

TGF-β:

Transforming growth factor beta

BMP:

Bone morphogenetic protein

IFN-γ:

Interferon gamma

References

  1. O’Rielly D, Rahman P (2011) Genetics of susceptibility and treatment response in psoriatic arthritis. Nat Rev Rheumatol 7:718–723

    Article  PubMed  Google Scholar 

  2. Lories RJ, de Vlam K (2012) Is psoriatic arthritis a result of abnormalities in acquired or innate immunity? Curr Rheumatol Rep 14:375–382

    Article  CAS  PubMed  Google Scholar 

  3. McGonagle D, Lories RJ, Tan AL et al (2007) The concept of a “synovio-entheseal complex” and its implications for understanding joint inflammation and damage in psoriatic arthritis and beyond. Arthritis Rheum 56:2482–2491

    Article  PubMed  Google Scholar 

  4. Yeremenko N, Noordenbos T, Cantaert T et al (2013) Disease-specific and inflammation-independent stromal alterations in spondyloarthritis synovitis. Arthritis Rheum 65:174–185

    Article  CAS  PubMed  Google Scholar 

  5. Nestle FO, Kaplan D, Barker J (2009) Psoriasis. N Engl J Med 361:496–509

    Article  CAS  PubMed  Google Scholar 

  6. Reveille JD (2012) Genetics of spondyloarthritis: beyond the MHC. Nat Rev Rheumatol 8:296–304

    Article  CAS  PubMed  Google Scholar 

  7. Chandran V, Raychaudhuri SP (2010) Geoepidemiology and environmental factors of psoriasis and psoriatic arthritis. J Autoimmun 34:J314–J321

    Article  CAS  PubMed  Google Scholar 

  8. Ogilvie AL, Luft M, Antoni C (2006) Leukocyte infiltration and mRNA expression of IL-20, IL-8 and TNF-R P60 in psoriatic skin is driven by TNF-alpha. Int J Immunopathol Pharmacol 19(2):271–278

    CAS  PubMed  Google Scholar 

  9. Gossec L, Smolen J, Gaujoux-Viala C et al (2012) European League Against Rheumatism recommendations for the management of psoriatic arthritis with pharmacological therapies. Ann Rheum Dis 71:4–12

    Article  CAS  PubMed  Google Scholar 

  10. Baechler EC, Batliwalla FM, Karypis G et al (2003) Interferon-inducible gene expression signature in peripheral blood cells of patients with severe lupus. Proc Natl Acad Sci U S A 100(5):2610–2615

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  11. Batliwalla FM, Baechler EC, Xiao X et al (2005) Peripheral blood gene expression profiling in rheumatoid arthritis. Genes Immun 6(5):388–397

    Article  CAS  PubMed  Google Scholar 

  12. Pimentel-Santos F, Ligeiro D, Matos M et al (2011) Whole blood transcriptional profiling in ankylosing spondylitis identifies novel candidate genes that might contribute to the inflammatory and tissue-destructive disease aspects. Arthritis Res Ther 13:R57

    Article  PubMed Central  PubMed  Google Scholar 

  13. Taylor WJ, Gladman DD, Helliwell PS et al (2006) Classification criteria for psoriatic arthritis: development of new criteria from a large international study. Arthritis Rheum 54:2665–2673

    Article  PubMed  Google Scholar 

  14. Gu J, Marker-Hermann E, Baeten D et al (2002) A 588-gene microarray analysis of the peripheral blood mononuclear cells of spondyloarthropathy patients. Rheumatology 41:759–766

    Article  CAS  PubMed  Google Scholar 

  15. Stoeckman AK, Baechler EC, Ortmann WA et al (2006) A distinct inflammatory gene expression profile in patients with psoriatic arthritis. Genes Immun 7:583–591

    Article  CAS  PubMed  Google Scholar 

  16. Batliwalla FM, Wentian L, Ritchlin C et al (2005) Microarray analysis of peripheral blood cells identifies unique gene expression signature in psoriatic arthritis. Mol Med 11:1–12

    Article  Google Scholar 

  17. Shi L, Perkins RG, Fang H et al (2008) Reproducible and reliable microarray results through quality controls: good laboratory proficiency and appropriate data analysis practices are essential. Curr Opin Biotechnol 19:10–18

    Article  CAS  PubMed  Google Scholar 

  18. Simon R (2008) Microarray-based expression profiling and informatics. Curr Opin Biotechnol 19:26–29

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  19. Van Kuijk AW, Reinders-Blankert P, Smeets TJ et al (2006) Detailed analysis of the cell infiltrate and the expression of mediators of synovial inflammation and joint destruction in the synovium of patients with psoriatic arthritis: implications for treatment. Ann Rheum Dis 65(12):1551–1557

    Article  PubMed Central  PubMed  Google Scholar 

  20. Mease P (2011) Psoriatic arthritis: update on pathophysiology, assessment and management. Ann Rheum Dis 70:i77–i84

    Article  PubMed  Google Scholar 

Download references

Acknowledgments

We would like to thank Ms. Jill Schurr for her assistance in the microarray analysis.

Conflict of interest

None.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Luis R. Espinoza.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Cuchacovich, R., Perez-Alamino, R., Zea, A.H. et al. Distinct genetic profile in peripheral blood mononuclear cells of psoriatic arthritis patients treated with methotrexate and TNF-inhibitors. Clin Rheumatol 33, 1815–1821 (2014). https://doi.org/10.1007/s10067-014-2807-8

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10067-014-2807-8

Keywords

Navigation