Gene Expression Profiling of Monozygotic Twins Affected by Psoriatic Arthritis

Overview

Journal Open Access Rheumatol

Publisher Dove Medical Press

Specialty Rheumatology

Date 2021 Mar 11

PMID 33692638

Citations 1

Authors

Maria Maddalena Angioni

Alberto Floris

Ignazio Cangemi

Mattia Congia

Elisabetta Chessa

Sandro Orru

Matteo Piga

Alberto Cauli

Affiliations

Soon will be listed here.

Abstract

Introduction: Psoriatic Arthritis (PsA) is a multifactorial disease, where the relative burden of genetic, epigenetic and environmental factors in clinical course and damage accrual is not yet definitively clarified. In clinical practice, there is a real need for useful candidate biomarkers in PsA diagnosis and disease progression, by exploring its underlying transcriptomic and epigenomic mechanisms. This work aims to profile the transcriptome in monozygotic (MZ) twins with psoriatic arthritis (PsA) highly concordant for clinical presentation, but discordant for the radiographic outcomes' severity.

Methods: We describe i) the clinical case of two MZ twins; ii) their comparative gene expression profiling (HTA 2.0 Affymetrix) and iii) signal pathways and pathophysiological processes in which differentially expressed genes are involved (in silico analysis by the IPA software, QIAGEN).

Results: One hundred sixty-three transcripts and 36 coding genes (28 up and 8 down) were differentially expressed between twins, and in the brother with the most erosive form, the transcriptomic profiling highlights the overexpression of genes known to be involved in immunomodulatory processes and on a broad spectrum of PsA manifestations.

Discussion: Twins' clinical cases are still a gold mine in medical research: twin brothers are ideal experimental models in estimating the relative importance of genetic versus nongenetic components as determinants of complex phenotypes, non-Mendelian and multifactorial diseases as PsA.

Citing Articles

Molecular profiling of clinical remission in psoriatic arthritis reveals dysregulation of and genes: a gene expression study.

Angioni M, Floris A, Cangemi I, Congia M, Chessa E, Naitza M Front Immunol. 2023; 14:1274539.

PMID: 37965313 PMC: 10641465. DOI: 10.3389/fimmu.2023.1274539.

References

Chandran V, Schentag C, Brockbank J, Pellett F, Shanmugarajah S, Toloza S . Familial aggregation of psoriatic arthritis. Ann Rheum Dis. 2008; 68(5):664-7. DOI: 10.1136/ard.2008.089367. View

Xiang Z, Yang Y, Chang C, Lu Q . The epigenetic mechanism for discordance of autoimmunity in monozygotic twins. J Autoimmun. 2017; 83:43-50. DOI: 10.1016/j.jaut.2017.04.003. View

Gray-Owen S, Blumberg R . CEACAM1: contact-dependent control of immunity. Nat Rev Immunol. 2006; 6(6):433-46. DOI: 10.1038/nri1864. View

Saito T, Fukai A, Mabuchi A, Ikeda T, Yano F, Ohba S . Transcriptional regulation of endochondral ossification by HIF-2alpha during skeletal growth and osteoarthritis development. Nat Med. 2010; 16(6):678-86. DOI: 10.1038/nm.2146. View

Floreani A, Leung P, Gershwin M . Environmental Basis of Autoimmunity. Clin Rev Allergy Immunol. 2015; 50(3):287-300. DOI: 10.1007/s12016-015-8493-8. View

Pedersen O, Svendsen A, Ejstrup L, Skytthe A, Junker P . On the heritability of psoriatic arthritis. Disease concordance among monozygotic and dizygotic twins. Ann Rheum Dis. 2008; 67(10):1417-21. DOI: 10.1136/ard.2007.078428. View

Moll J, WRIGHT V . Familial occurrence of psoriatic arthritis. Ann Rheum Dis. 1973; 32(3):181-201. PMC: 1006078. DOI: 10.1136/ard.32.3.181. View

Davidson R, Waters J, Kevorkian L, Darrah C, Cooper A, Donell S . Expression profiling of metalloproteinases and their inhibitors in synovium and cartilage. Arthritis Res Ther. 2006; 8(4):R124. PMC: 1779413. DOI: 10.1186/ar2013. View

Zheng Z, Nguyen C, Zhang X, Khorasani H, Wang J, Zara J . Delayed wound closure in fibromodulin-deficient mice is associated with increased TGF-β3 signaling. J Invest Dermatol. 2010; 131(3):769-78. PMC: 4073663. DOI: 10.1038/jid.2010.381. View

10.

Zhao L, Furebring M, Xu S, Venge P . Subcellular localization and mobilization of carcinoembryonic antigen-related cell adhesion molecule 8 in human neutrophils. Br J Haematol. 2004; 125(5):666-73. DOI: 10.1111/j.1365-2141.2004.04963.x. View

11.

Lorentzen J, Flornes L, Eklow C, Backdahl L, Ribbhammar U, Guo J . Association of arthritis with a gene complex encoding C-type lectin-like receptors. Arthritis Rheum. 2007; 56(8):2620-32. DOI: 10.1002/art.22813. View

12.

Ooms L, Horan K, Rahman P, Seaton G, Gurung R, Kethesparan D . The role of the inositol polyphosphate 5-phosphatases in cellular function and human disease. Biochem J. 2009; 419(1):29-49. DOI: 10.1042/BJ20081673. View

13.

Selmi C, Lu Q, Humble M . Heritability versus the role of the environment in autoimmunity. J Autoimmun. 2012; 39(4):249-52. DOI: 10.1016/j.jaut.2012.07.011. View

14.

Park H, Kim Y, Yu B, Moroishi T, Mo J, Plouffe S . Alternative Wnt Signaling Activates YAP/TAZ. Cell. 2015; 162(4):780-94. PMC: 4538707. DOI: 10.1016/j.cell.2015.07.013. View

15.

Streicher K, Morehouse C, Groves C, Rajan B, Pilataxi F, Lehmann K . The plasma cell signature in autoimmune disease. Arthritis Rheumatol. 2014; 66(1):173-84. DOI: 10.1002/art.38194. View

16.

Rahman P, Elder J . Genetic epidemiology of psoriasis and psoriatic arthritis. Ann Rheum Dis. 2005; 64 Suppl 2:ii37-9. PMC: 1766868. DOI: 10.1136/ard.2004.030775. View

17.

Sjoberg A, Onnerfjord P, Morgelin M, Heinegard D, Blom A . The extracellular matrix and inflammation: fibromodulin activates the classical pathway of complement by directly binding C1q. J Biol Chem. 2005; 280(37):32301-8. DOI: 10.1074/jbc.M504828200. View

18.

Coates L, Fransen J, Helliwell P . Defining minimal disease activity in psoriatic arthritis: a proposed objective target for treatment. Ann Rheum Dis. 2009; 69(1):48-53. DOI: 10.1136/ard.2008.102053. View

19.

De Preter V, Rutgeerts P, Schuit F, Verbeke K, Arijs I . Impaired expression of genes involved in the butyrate oxidation pathway in Crohn's disease patients. Inflamm Bowel Dis. 2012; 19(3):E43-4. DOI: 10.1002/ibd.22970. View

20.

Zhu W, Trivedi C, Zhou D, Yuan L, Lu M, Epstein J . Inpp5f is a polyphosphoinositide phosphatase that regulates cardiac hypertrophic responsiveness. Circ Res. 2009; 105(12):1240-7. PMC: 2802340. DOI: 10.1161/CIRCRESAHA.109.208785. View