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A6.19 Identification of an unexpected dysregulated pathway by transcriptomic analysis of monocyte-derived dendritic cells (MD-DCS) in spondyloarthritis (SPA) patients
  1. C Desjardin1,
  2. C Hue1,
  3. S Grassin-Delyle2,
  4. H-J Garchon1,
  5. E Chaplais1,
  6. M Breban1,
  7. G Chiocchia1
  1. 1INSERM U1173, UFR Sciences de La Santé Simone Veil, Université Versailles Saint Quentin en Yvelines, 2, Avenue de La Source de La Bièvre 78180 Montigny-Le-Bretonneux
  2. 2UVSQ, Plateforme de Spectrométrie de Masse MasSpecLab, UFR Sciences de La Santé Simone Veil, Université Versailles Saint Quentin en Yvelines, 2, Avenue de La Source de La Bièvre, 78180 Montigny-Le-Bretonneux

Abstract

Background Spondyloarthritis (SpA) is one of the most frequent chronic inflammatory rheumatisms that affects axial skeleton, peripheral joints and may result in ankylosis of the spine and sacroiliac joints. Extra-articular features including uveitis, psoriasis and inflammatory bowel disease are frequent. Current SpA treatments are only symptomatic, relieving inflammatory symptoms. SpA aetiology is largely multifactorial with a genetic component dominated by the association with the HLA-B27 allele. This allele, however, is not sufficient for the disease to occur. Whereas dendritic cells (DCs) are believed to play a key role in SpA pathogenesis, the precise mechanisms underlying disease development and the role of HLA-B27 remain poorly understood. To shed light on the genes involved, we recently carried out a transcriptomic analysis of monocyte-derived DCs (MD-DCs) from patients and healthy controls, also accounting for HLA-B27.

Material and methods Transcriptomic profiles of MD-DCs were obtained with the Affymetrix Human Gene 1.0 ST technology from SpA patients (n = 23 HLA-B27+) and from healthy controls (n = 23 HLA-B27+, n = 21 HLA-B27-). Analysis of differentially expressed (DE) genes was conducted with LIMMA accounting for both the disease and the HLA-B27 status, followed by quantitative gene set enrichment analyses (quSAGE) and functional annotation. We performed three comparisons to identify DE genes and generating three lists: A, including 800 DE genes between SpA patients and HLA-B27- controls; B, including 673 DE genes between HLA-B27+ controls and HLA-B27- controls; and C, including 466 DE genes between SpA patients and HLA-B27+ controls. Subtracting A–B left 656 genes, of which 68 are in list C.

Results By combining a transcriptomic analysis and innovative comparative approaches, we identified a set of 68 genes affected by SpA overcoming the potential HLA-B27 effect. Based on functional annotation, those genes are mainly related to lipid synthesis, regulation and trafficking suggesting that MD-DCs from SpA patients exhibit major functional dysregulations.

Conclusion In SpA patients, DCs present a defect in lipid intracellular regulation and signalling which may be involved in SpA physiopathology and may contribute to its development and progression. Our work may help to improve the understanding of SpA pathogenesis and open new perspectives in therapeutic approaches.

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