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Altered gut transcriptome in spondyloarthropathy

D Laukens¹, H Peeters², B V Cruyssen³, T Boonefaes¹, D Elewaut³, F De Keyser³, H Mielants³, C Cuvelier⁴, E M Veys³, K Knecht⁵, P Van Hummelen⁶, E Remaut¹, L Steidler⁷, M De Vos², P Rottiers¹

¹ Department for Molecular Biomedical Research, Flanders Interuniversity Institute for Biotechnology (VIB), Ghent, Belgium
² Department of Gastroenterology, Ghent University Hospital, Ghent
³ Department of Rheumatology, Ghent University Hospital
⁴ Department of Pathology, Ghent University Hospital
⁵ Applied Maths BVBA, Sint-Martens-Latem, Belgium
⁶ MicroArray Facility, Flanders Interuniversity Institute for Biotechnology, Leuven, Belgium
⁷ Alimentary Pharmabiotic Centre, University College Cork, Cork, Ireland

Correspondence to:
D Laukens
Department for Molecular Biomedical Research, Ghent University, Technologiepark 927, B-9052 Ghent (Zwijnaarde), Belgium;debby.laukens{at}dmbr.Ugent.be

Background: Intestinal inflammation is a common feature of spondyloarthropathy (SpA) and Crohn’s disease. Inflammation is manifested clinically in Crohn’s disease and subclinically in SpA. However, a fraction of patients with SpA develops overt Crohn’s disease.

Aims: To investigate whether subclinical gut lesions in patients with SpA are associated with transcriptome changes comparable to those seen in Crohn’s disease and to examine global gene expression in non-inflamed colon biopsy specimens and screen patients for differentially expressed genes.

Methods: Macroarray analysis was used as an initial genomewide screen for selecting a comprehensive set of genes relevant to Crohn’s disease and SpA. This led to the identification of 2625 expressed sequence tags that are differentially expressed in the colon of patients with Crohn’s disease or SpA. These clones, with appropriate controls (6779 in total), were used to construct a glass-based microarray, which was then used to analyse colon biopsy specimens from 15 patients with SpA, 11 patients with Crohn’s disease and 10 controls.

Results: 95 genes were identified as differentially expressed in patients with SpA having a history of subclinical chronic gut inflammation and also in patients with Crohn’s disease. Principal component analysis of this filtered set of genes successfully distinguished colon biopsy specimens from the three groups studied. Patients with SpA having subclinical chronic gut inflammation cluster together and are more related to those with Crohn’s disease.

Conclusion: The transcriptome in the intestine of patients with SpA differs from that of controls. Moreover, these gene changes are comparable to those seen in patients with Crohn’s disease, confirming initial clinical observations. On the basis of these findings, new (genetic) markers for detection of early Crohn’s disease in patients with SpA can be considered.

Abbreviations: ACOXI, Acyl-coenzyme A oxidase 1; EST, expressed sequence tag; IBD, inflammatory bowel disease; PCR, polymerase chain reaction; SpA, spondyloarthropathy

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