Objective: To validate and refine two sets of candidate criteria for the classification/diagnosis of axial spondyloarthritis (SpA). Methods: All Assessment of SpondyloArthritis international Society (ASAS) members were invited to include consecutively new patients with chronic (>3 months) back pain of unknown origin that began before 45 years of age. The candidate criteria were first tested in the entire cohort of 649 patients from 25 centres, and then refined in a random selection of 40% of cases and thereafter validated in the remaining 60%. Results: Upon diagnostic work-up, axial SpA was diagnosed in 60.2% of the cohort. Of these, 70% did not fulfil modified New York criteria and, therefore, were classified as having ''non-radiographic'' axial SpA. Refinement of the candidate criteria resulted in new ASAS classification criteria that are defined as: the presence of sacroiliitis by radiography or by magnetic resonance imaging (MRI) plus at least one SpA feature (''imaging arm'') or the presence of HLA-B27 plus at least two SpA features (''clinical arm''). The sensitivity and specificity of the entire set of the new criteria were 82.9% and 84.4%, and for the imaging arm alone 66.2% and 97.3%, respectively. The specificity of the new criteria was much better than that of the European Spondylarthropathy Study Group criteria modified for MRI (sensitivity 85.1%, specificity 65.1%) and slightly better than that of the modified Amor criteria (sensitivity 82.9, specificity 77.5%). Conclusion:The new ASAS classification criteria for axial SpA can reliably classify patients for clinical studies and may help rheumatologists in clinical practice in diagnosing axial SpA in those with chronic back pain. Trial registration number: NCT00328068.

Objective To evaluate new classifi cation criteria for peripheral spondyloarthritis (SpA) in patients with SpA with peripheral manifestations only. Methods In this Assessment of SpondyloArthritis international Society (ASAS) study, two prespecifi ed sets of criteria were compared against the European Spondylarthropathy Study Group (ESSG) and Amor criteria in newly referred consecutive patients with undiagnosed peripheral arthritis, and/or enthesitis, and/ or dactylitis that usually began before 45 years of age. The clinical diagnosis (SpA vs no SpA) made by the ASAS rheumatologist served as reference standard. Results In all, 24 ASAS centres included 266 patients, with a fi nal diagnosis of SpA being made in 66.2%. After adjustments a fi nal set of criteria showed the best balance between sensitivity (77.8%) and specifi city (82.9%): arthritis and/or enthesitis and/or dactylitis plus (A) one or more of the following parameters: psoriasis, infl ammatory bowel disease, preceding infection, human leucocyte antigen B27, uveitis, sacroiliitis on imaging, or (B) two or more other parameters: arthritis, enthesitis, dactylitis, infl ammatory back pain in the past, family history of SpA. The new criteria performed better than modifi ed versions of the ESSG (sensitivity 62.5%, specifi city 81.1%) and the Amor criteria (sensitivity 39.8%, specifi city 97.8%), particularly regarding sensitivity. In the entire ASAS population of 975 patients the combined use of ASAS criteria for axial SpA and ASAS criteria for peripheral SpA also had a better balance (sensitivity 79.5%, specifi city 83.3%) than the modifi ed ESSG (sensitivity 79.1%, specifi city 68.8%) and Amor criteria (sensitivity 67.5%, specifi city 86.7%), respectively. Conclusions The new ASAS classifi cation criteria for peripheral SpA performed well in patients presenting with peripheral arthritis, enthesitis and/or dactylitis.

Sphingosine kinase (SphK) is a key enzyme in the sphingolipid metabolic pathway responsible for phosphorylating sphingosine into sphingosine-1-phosphate (S1P). SphK/S1P play a critical role in angiogenesis, inflammation, and various pathologic conditions. Recently, S1P1 receptor was found to be expressed in rheumatoid arthritis (RA) synovium, and S1P signaling via S1P1 enhances synoviocyte proliferation, COX-2 expression, and prostaglandin E2 production. Here, we examined the role of SphK/S1P in RA using a potent SphK inhibitor, N,N-dimethylsphingosine (DMS), and a molecular approach against one of its isoenzymes, SphK1. We observed that levels of S1P in the synovial fluid of RA patients were significantly higher than those of osteoarthritis patients. Additionally, DMS significantly reduced the levels of TNF-α, IL-6, IL-1β, MCP-1, and MMP-9 in cell-contact assays using both Jurkat-U937 cells and RA PBMCs. In a murine collagen-induced arthritis model, i.p. administration of DMS significantly inhibited disease severity and reduced articular inflammation and joint destruction. Treatment of DMS also down-regulated serum levels IL-6, TNF-α, IFN-γ, S1P, and IgG1 and IgG2a anti-collagen Ab. Furthermore, DMS-treated mice also displayed suppressed proinflammatory cytokine production in response to type II collagen in vitro. Moreover, similar reduction in incidence and disease activity was observed in mice treated with SphK1 knock-down via small interfering RNA approach. Together, these results demonstrate SphK modulation may provide a novel approach in treating chronic autoimmune conditions such as RA by inhibiting the release of pro-inflammatory cytokines.

This study shows that individuals with pre-RA have significant inflammatory periodontal involvement. There was a significant association between IgG against P. gingivalis and ACPAs in pre-RA and markers of RA activity in individuals with eRA.

The PPV of the axSpA and pSpA criteria to forecast an expert's diagnosis of 'SpA' after more than 4 years is excellent. The 'imaging arm' and 'clinical arm' of the axSpA criteria have similar predictive validity and are truly complementary.

Different pharmacological treatments for RA affect the clinical condition and subgingival microbiota.

The aim of this study was to investigate the body mass index (BMI), anti-citrullinated protein antibodies (ACPAs) status and the presence of periodontitis and IgG-1/IgG-2 antibodies against Porphyromonas gingivalis (Pg) in the first-degree relatives (FDRs) of rheumatoid arthritis (RA) patients and compare these variables with a control group of healthy individuals from the general population. In total, 100 FDR individuals and 200 healthy controls matched by age and gender were included. Rheumatologic and periodontal assessment was performed, and the presence of ACPAs and anti-P. gingivalis antibodies was evaluated. Groupwise comparisons were analysed using the McNemar and Wilcoxon tests. A conditional logistic regression analysis was performed to establish the associations between BMI, ACPAs and periodontitis in both groups. In the FDR group, 70% of the subjects were female, with a mean age of 37.3 ± 13 years. Obesity was observed in 17 and 7% of the FDRs and controls, respectively. ACPAs were found in 7% of the FDRs vs. 2.5% of the controls. Periodontitis was diagnosed in 79 and 56% of the FDRs and controls, respectively. Among the FDRs, 15% had severe periodontitis. There were associations in the FDR group related to the presence of obesity (OR 2.93, 95% CI 1.03-8.28), ACPAs (OR 2.45, 95% CI 0.7-8.32) and periodontitis (OR 3.70 95% CI 1.89-7.29). Regarding anti-P. gingivalis antibodies and smoking history, no differences were found between the groups. Obesity, ACPAs and periodontitis (diagnosis and severity) can be considered as relevant conditions associated with the development of RA in FDRs.

Although most ankylosing spondylitis patients show an apparent clinical response to infliximab therapy, there is considerable individual variation. Because current clinical assessment relies heavily on subjective patient self-evaluation, biomarkers of high sensitivity and specificity are much needed. Here, we assessed potential biomarkers in 47 ankylosing spondylitis patients who received three standard pulses of infliximab. Before each infusion and at week 10, the following were measured: erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), platelet count, serum levels of metalloproteinase-3 (MMP-3), and 22 different cytokines. We discovered that, 2 weeks after the first infusion, the combination of ESR, CRP, and platelet count distinguished responders from non-responders with 81.3% sensitivity and 72.7% specificity. The distinguishing power was much less when each acute phase reactant was used alone. Among the 22 cytokines, serum IL-1alpha was able to distinguish responders from non-responders at week 6, with sensitivity of 84.9% and specificity of 53.8%. Serum IL-1alpha was probably generated from the joint compartments, as synovial fluid levels were much higher than corresponding serum levels. Although infliximab infusions led to rapid and significant suppression of serum MMP-3 levels, serum MMP-3 levels did not distinguish responders from non-responders. Besides identifying potential biomarkers, our results also demonstrate the usefulness of using sensitivity and specificity to assess usefulness of potential biomarkers.