STAT1 deficiency underlies a proinflammatory imprint of naive CD4 T cells in spondyloarthritis.

Introduction: In spondyloarthritis (SpA), an increased type 3 immune response, including T helper cells (Th) 17 excess, is observed in both human and SpA animal models, such as the HLA-B27/human β2-microglobulin transgenic rat (B27-rat).

Methods: To investigate this unexplained Th17-biased differentiation, we focused on understanding the immunobiology of B27-rat naive CD4 T cells (Tn).

Results: We observed that neutrally stimulated B27-rat Tn developed heightened Th17 profile even before disease onset, suggesting an intrinsic proinflammatory predisposition.

Both Disease Activity and HLA-B27 Status Are Associated With Gut Microbiome Dysbiosis in Spondyloarthritis Patients.

Objective: Gut microbiome dysbiosis has previously been reported in spondyloarthritis (SpA) patients and could be critically involved in the pathogenesis of this disorder. The objectives of this study were to further characterize the microbiota structure in SpA patients and to investigate the relationship between dysbiosis and disease activity in light of the putative influence of the genetic background.

Methods: Shotgun sequencing was performed on fecal DNA isolated from stool samples from 2 groups of adult volunteers: SpA patients (n = 102) and healthy controls (n = 63).

Targeted resequencing of the 13q13 spondyloarthritis-linked locus identifies a rare variant in FREM2 possibly associated with familial spondyloarthritis.

Objectives: The strong heritability of spondyloarthritis remains poorly explained, despite several large-scale association studies. A recent linkage analysis identified a new region linked to SpA on 13q13. Here we searched for variants potentially explaining this linkage signal by deep-sequencing of the region.

Rheumatoid arthritis, as a clinical disease, but not rheumatoid arthritis-associated autoimmunity, is linked to cardiovascular events.

Background: Rheumatoid arthritis (RA) is characterized by increased cardiovascular (CV) mortality. CV events are particularly high in patients with RA-specific autoimmunity, including rheumatoid factor (RF) and anti-citrullinated protein antibodies (ACPA), raising the question whether RA-specific autoimmunity itself is associated with CV events.

Methods: New CV events (myocardial infarction, stroke or death by CV cause) were recorded in 20,625 subjects of the Electricité de France - Gaz de France (GAZEL) cohort.

What Have We Learned From Family-Based Studies About Spondyloarthritis?

Spondyloarthritis (SpA) is a chronic inflammatory disorder with a high familial aggregation, emphasizing the existence of genetic susceptibility factors. In the last decades, family-based studies have contributed to better understand the genetic background of SpA, in particular by showing that the most likely model of transmission is oligogenic with multiplicative effects. Coexistence of different SpA subtypes within families also highlighted the complex interplay between all subtypes.

Abrupt and unexpected stressful life events are followed with increased disease activity in spondyloarthritis: A two years web-based cohort study.

Objective: The contribution of environmental factors to spondyloarthritis (SpA) course remains poorly characterized. We previously reported a possible triggering of disease flares by stressful life events and vaccination. The objective of the present study was to specify the types of vaccine and life event that may influence disease activity.

Faecal microbiota study reveals specific dysbiosis in spondyloarthritis.

Objective: Altered microbiota composition or dysbiosis is suspected to be implicated in the pathogenesis of chronic inflammatory diseases, such as spondyloarthritis (SpA) and rheumatoid arthritis (RA).

Methods: 16S ribosomal RNA gene sequencing was performed on faecal DNA isolated from stool samples in two consecutive cross-sectional cohorts, each comprising three groups of adult volunteers: SpA, RA and healthy controls (HCs). In the second study, HCs comprised a majority of aged-matched siblings of patients with known HLA-B27 status.

Radiographic sacroiliitis develops predictably over time in a cohort of familial spondyloarthritis followed longitudinally.

Objectives: Radiographic sacroiliitis is an important outcome in SpA and is considered a hallmark to ascertain the diagnosis of AS. The aim of the current study was to investigate factors associated with the presence of radiographic sacroiliitis at baseline and the predictors of progression to AS in a family cohort of SpA.

Methods: A total of 953 patients fulfilling the Assessment of SpondyloArthritis international Society criteria for SpA and having at least one first- or second-degree SpA-affected relative were included.

A family-based genome-wide association study reveals an association of spondyloarthritis with MAPK14.

Objective: More than 40 loci have been associated with ankylosing spondylitis (AS), but less is known about genetic associations in spondyloarthritis (SpA) as a whole. We conducted a family-based genome-wide association study (GWAS) to identify new non-major histocompatibility complex (MHC) genetic factors associated with SpA.

Methods: 906 subjects from 156 French multiplex families, including 438 with SpA, were genotyped using Affymetrix 250K microarrays.

Whole-genome single nucleotide polymorphism-based linkage analysis in spondyloarthritis multiplex families reveals a new susceptibility locus in 13q13.

Objective: Spondyloarthritis (SpA) is a chronic inflammatory disorder with high heritability but with complex genetics. Apart from HLA-B27, most of the underlying genetic components remain to be identified. We conducted a whole-genome high-density non-parametric linkage analysis to identify new genetic factors of susceptibility to SpA.

ERAP1 Gene Expression Is Influenced by Nonsynonymous Polymorphisms Associated With Predisposition to Spondyloarthritis.

Objective: Several polymorphisms in ERAP1 are strongly associated with susceptibility to spondyloarthritis (SpA). The combination of rs17482078, rs10050860, and rs30187 results in the construction of 3 major haplotypes that are associated with SpA (the "protective" haplotype T/T/C, the "neutral" haplotype C/C/C, and the "susceptibility" haplotype C/C/T). The aim of the present study was to determine whether such haplotypes might affect endoplasmic reticulum aminopeptidase 1 (ERAP-1) messenger RNA (mRNA) expression, protein level, and/or enzymatic activity in antigen-presenting cells, a type of cell that is potentially relevant to disease pathogenesis.

Prevalence of spondyloarthritis in reference to HLA-B27 in the French population: results of the GAZEL cohort.

Objective: To estimate the prevalence of spondyloarthritis (SpA) in reference to HLA-B27 in the French population.

Methods: In 1989, 20 625 employees of the French national gas and electricity company aged 35-50 years were enrolled in the GAZEL cohort. In 2010, 18 757 still active participants were screened by a questionnaire validated for the detection of SpA.

Brief report: the IL23R nonsynonymous polymorphism rs11209026 is associated with radiographic sacroiliitis in spondyloarthritis.

Objective: Spondyloarthritis (SpA) is a group of inflammatory articular disorders sharing a genetic background. The nonsynonymous single-nucleotide polymorphism (SNP) rs11209026 (Arg381Gln) in the IL23R gene has reproducibly been shown to be associated with ankylosing spondylitis (AS). We undertook this study to examine the association between rs11209026 and SpA as a whole, with particular attention devoted to genotype/phenotype correlation.

Influence of environmental factors on disease activity in spondyloarthritis: a prospective cohort study.

Objective: Spondyloarthritis (SpA) is a complex inflammatory disorder. We investigated the influence of environmental factors on SpA disease activity.

Methods: A prospective cohort of adults with SpA was followed for 3 years.

Investigating the genetic association between ERAP1 and spondyloarthritis.

Objective: A robust association between polymorphisms in the non-major histocompatibility complex gene ERAP1 and ankylosing spondylitis (AS) in several populations was recently identified. The aim of the current study was to determine the level of association of ERAP1 polymorphisms with spondyloarthritis (SpA) in French/Belgian populations with particular attention to genotype-phenotype correlations.

Methods: We studied 734 independent SpA cases and 632 controls from two European cohorts.

Can we improve the diagnosis of spondyloarthritis in patients with uncertain diagnosis? The EchoSpA prospective multicenter French cohort.

Unlabelled: Power Doppler ultrasound (PDUS) has proved to be a highly sensitive tool for assessing enthesitis in spondyloarthritis (SpA). In patients with a suspected SpA, diagnosis could be improved by detecting enthesitis with PDUS.

Objective: To evaluate the performance of PDUS for the diagnosis of SpA alone or combined with other clinical, laboratory and imaging findings in patients consulting for a suspected SpA.

Association between the IL-1 family gene cluster and spondyloarthritis.

Objective: Spondyloarthritis is a group of articular disorders sharing a genetic background. Polymorphisms in the IL-1 gene cluster have previously been associated with ankylosing spondylitis (AS), a subset of spondyloarthritis. This study examined the association between several of these polymorphisms and the whole spondyloarthritis.

Systematic candidate gene investigations in the SPA2 locus (9q32) show an association between TNFSF8 and susceptibility to spondylarthritis.

Objective: Our group previously identified a new susceptibility region linked to spondylarthritis (SpA) on chromosome 9q31-34. Fine mapping of this SPA2 locus allowed us to refine the peak of linkage to a 1.3-Mb interval.

Prospective assessment of thoracic kyphosis in postmenopausal women with osteoporosis.

We attempt to assess quantitatively thoracic kyphosis and its influence on incident fractures and quality of life over three years in postmenopausal women with osteoporosis and the effect of strontium ranelate on thoracic kyphosis progression. This study was performed on women with postmenopausal osteoporosis from the Spinal Osteoporosis Therapeutic Intervention (SOTI) and Treatment of Peripheral Osteoporosis (TROPOS) studies. Vertebral fractures were assessed on lateral thoracic radiographs performed at baseline and at three years according to standardized procedure.

Comprehensive linkage and association analyses identify haplotype, near to the TNFSF15 gene, significantly associated with spondyloarthritis.

Spondyloarthritis (SpA) is a chronic inflammatory disorder with a strong genetic predisposition dominated by the role of HLA-B27. However, the contribution of other genes to the disease susceptibility has been clearly demonstrated. We previously reported significant evidence of linkage of SpA to chromosome 9q31-34.

The genetics of spondyloarthropathies.

The spondyloarthropathies constitute a group of inflammatory joint diseases linked by shared characteristics that include a strong common genetic background. Genetic factors include major histocompatibility complex (MHC) genes, among which HLA-B27 contributes 30% of the overall genetic susceptibility to spondyloarthropathies, and non-MHC genes, none of which have been identified to date. Genome screens have identified regions that may contain susceptibility genes for spondyloarthropathies.

Two major spondylarthropathy phenotypes are distinguished by pattern analysis in multiplex families.

Objective: To examine whether spondylarthropathy (SpA) disease manifestations would combine in any ordered pattern among patients from SpA multiplex families.

Methods: SpA patients (n = 540) belonging to 190 multiplex families were thoroughly investigated. Clinical data was collected, systematic pelvic radiographs were taken, and HLA-B27 status was determined.

Significant linkage to spondyloarthropathy on 9q31-34.

Spondyloarthropathy (SpA) is a frequent rheumatologic disorder with a prevalence of 0.3% in Caucasian populations from western Europe. It commonly presents as chronic axial and/or peripheral arthritis with potential disabling outcome.

Familial and genetic aspects of spondyloarthropathy.

Predisposition to SpA is largely determined by genetic factors including HLA-B27 and other as yet unknown genes that might be tracked by a positional cloning approach. Analysis performed on a large cohort of SpA multiplex families revealed that the different articular and extra-articular inflammatory manifestations comprising the SpA spectrum were linked together, implying that they were determined by a shared set of factors, including HLA-B27. The variety of phenotypes appeared to be related to ubiquitous and secondary factors.

Assessment of peripheral enthesitis in the spondylarthropathies by ultrasonography combined with power Doppler: a cross-sectional study.

Objective: To assess the prevalence and severity of peripheral enthesitis among the different subtypes of spondylarthropathy (SpA) by using ultrasonography (US) in B mode with power Doppler.

Methods: One hundred sixty-four consecutive patients with SpA (according to the criteria of the European Spondylarthropathy Study Group) and 64 control patients (34 with mechanical low back pain [MBP] and 30 with rheumatoid arthritis [RA]) underwent US examination of major entheses of their limbs. Particular attention was given to the detection of vascularization at the following sites: cortical bone insertion of entheses, junction between tendon and entheses, body of tendon, and bursa.