Identification of distinct gene expression profiles in the synovium of patients with systemic lupus erythematosus

Toukap, A. Nzeusseu; Galant, Christine; Théate, Ivan; Maudoux, Anne‐Lise; Lories, Rik; Houssiau, Frédéric; Lauwerys, Bernard

doi:10.1002/art.22578

Cited by 170 publications

(91 citation statements)

References 12 publications

(12 reference statements)

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“…In most inflammatory conditions an upregulation of inflammation-associated genes would be expected, such as in RA and systemic lupus erythematosus. [147][148][149][150][151] Our results however are consistent with the macrophage study described above which also detailed a decreased immune response. 142 They also saw a decrease in TNFAIP3 expression in AS patients.…”

Section: Circulating Cell Studiessupporting

confidence: 92%

The genomics and genetics of ankylosing spondylitis

Kenna¹,

Davidson²,

Thomas³

2011

AGG

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Abstract:The spondyloarthropathies are a group of arthritides which specifically target the spine and pelvis with ankylosing spondylitis (AS) being the most prevalent and debilitating of these conditions. Unique to AS is the progression to excessive uncontrolled bone formation following an initial inflammatory phase that can result in joint fusion and significant disability. Spondyloarthritis is estimated to affect 1%-2% of the population, twice as many as rheumatoid arthritis and thus constitutes a significant health problem. Currently AS pathogenesis is very poorly understood but recent large-scale genetics and gene expression profiling studies have identified some of the underlying mechanisms and pathways contributing to the disease. Genome-wide association studies have identified a number of candidate genes associated with AS sharing the same pathways which are now being targeted for therapeutic intervention. However, although such approaches can identify genes contributing to the disease process and are very informative as to disease aetiopathogenesis, they cannot profile the actual changes in gene/cell activity at any point in the disease process or possibly more importantly at specific sites. Such information is generated using expression profiling. A number of expression profiling studies have been undertaken in AS, looking at both circulating cells and tissues from affected joints. Although some common genes/pathways have been identified, overall the results to date have been somewhat disappointing due to differences in experimental design and tissue source as well as the low power of the studies. More recent better powered studies have shown some potential in developing gene expression profiling as a diagnostic tool in AS. True future success will rely on larger genetic and genomic studies and the combination of these datasets in eQTL studies requiring significant collaborative efforts. Such larger-scale approaches will also generate sufficient power to target specific disease stages and sites.

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Section: Circulating Cell Studiessupporting

confidence: 92%

The genomics and genetics of ankylosing spondylitis

Kenna¹,

Davidson²,

Thomas³

2011

AGG

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“…All SLE patients had active disease, and their mean score on the SLE Disease Activity Index (SLEDAI) (32) was 17 (range [7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26]. SLE patients had a mean C-reactive protein (CRP) level of 5.7 mg/liter, and a mean erythrocyte sedimentation rate (ESR) of 40 mm/hour.…”

Section: Methodsmentioning

confidence: 99%

Sialic acid–binding Ig‐like lectin 1 expression in inflammatory and resident monocytes is a potential biomarker for monitoring disease activity and success of therapy in systemic lupus erythematosus

Biesen¹,

Demir²,

Barkhudarova³

et al. 2008

Arthritis & Rheumatism

175

149

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Objective. Type I interferon (IFN) plays a pivotal role in the pathogenesis of systemic lupus erythematosus (SLE) and is therefore considered a potential therapeutic target. This study was undertaken to establish a feasible biomarker for IFN effects with respect to disease activity and effectiveness of IFN-suppressive therapy in SLE patients.Methods. Transcriptomes of purified monocytes from 9 SLE patients and 7 healthy controls were analyzed by Affymetrix GeneChip technology. Levels of sialic acid-binding Ig-like lectin 1 (Siglec-1) (sialoadhesin, CD169) in inflammatory and resident monocytes were determined at the protein level in 38 healthy controls and 52 SLE patients, using multicolor flow cytometry.Results. Transcriptomes of peripheral monocytes from SLE patients revealed a dominant type I IFN signature. Siglec-1 was identified as one of the most prominent type I IFN-regulated candidate genes. At the protein level, the frequency of Siglec-1-expressing monocyte subsets was correlated with disease activity (as measured by the SLE Disease Activity Index) and was inversely correlated with levels of complement factors. Most interestingly, levels of anti-doublestranded DNA (anti-dsDNA) antibodies were highly correlated with the percentage of resident monocytes, but not inflammatory monocytes, expressing Siglec-1. High-dose glucocorticoid treatment resulted in a dramatic reduction of Siglec-1 expression in cells from patients with active SLE.Conclusion. Our findings indicate that Siglec-1 expression in resident blood monocytes is a potential biomarker for monitoring disease activity, displaying type I IFN responses, and estimating levels of antidsDNA antibodies. Moreover, our results suggest that resident and inflammatory monocytes contribute differently to the process of autoantibody formation in SLE.

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“…FAP␣ expression is associated with arthritis, and we have shown active FAP␣ on the surface of chondrocytes and elevated expression in OA cartilage compared with control carti-lage (137). FAP␣ is also present in OA and RA synovial tissue (138,139), and elevated expression is detected in murine CIA (140). Unlike DPP-4, FAP␣ has gelatinolytic activity and thus may contribute to ECM degradation, although the exact mechanistic role of FAP␣ in arthritis (and indeed other pathologies) is unknown.…”

Section: )mentioning

confidence: 99%