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Ankylosing spondylitis (AS) remains difficult to diagnose before irreversible damage to sacroiliac joint is noticeable. Circulating microRNAs have demonstrated to serve as diagnostic tools for several human diseases. Here, we analysed plasma microRNAs to identify potential AS biomarkers. Higher expression levels of microRNA (miR)-146a-5p, miR-125a-5p, miR-151a-3p and miR-22-3p, and lower expression of miR-150-5p, and miR-451a were found in AS versus healthy donors. Interestingly, higher miR-146a-5p, miR-125a-5p, miR-151a-3p, miR-22-3p and miR-451a expression was also observed in AS than psoriatic arthritis patients. The areas under the curve, generated to assess the accuracy of microRNAs as diagnostic biomarkers for AS, ranged from 0.614 to 0.781; the six-microRNA signature reached 0.957. Bioinformatics analysis revealed that microRNAs targeted inflammatory and bone remodeling genes, underlying their potential role in this pathology. Indeed, additional studies revealed an association between these six microRNAs and potential target proteins related to AS pathophysiology. Furthermore, miR-146a-5p, miR-125a-5p and miR-22-3p expression was increased in active versus non-active patients. Moreover, miR-125a-5p, miR-151a-3p, miR-150-5p and miR-451a expression was related to the presence of syndesmophytes in AS patients. Overall, this study identified a six-plasma microRNA signature that could be attractive candidates as non-invasive biomarkers for the AS diagnosis, and may help to elucidate the disease pathogenesis.

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The aim of this study was to investigate the microRNA (miRNA) expression pattern in neutrophils from rheumatoid arthritis (RA) patients and its contribution to their pathogenic profile and to analyze the effect of specific autoantibodies or inflammatory components in the regulation of miRNA in RA neutrophils and its modulation by biological therapies. Neutrophils were isolated from paired peripheral blood (PB) and synovial fluid samples of 40 patients with RA and from PB of 40 healthy donors. A miRNA array was performed using nCounter technology. Neutrophils from healthy donors were treated in vitrowith antibodies to citrullinated protein antigens isolated from RA patients and tumor necrosis factor-a (TNF-a) or interleukin-6. A number of cytokines and chemokines were analyzed. In vitro treatments of RA-neutrophils with tocilizumab or infliximab were carried out. Transfections with pre-miRNA and DICER downregulation experiments were further performed. RA-neutrophils showed a global downregulation of miRNA and genes involved in their biogenesis, alongside with an upregulation of various potential mRNA targets related to migration and inflammation. Decreased levels of miRNA and DICER correlated with autoimmunity, inflammation and disease activity. Citrullinated protein antigens and TNF-a decreased the expression of numerous miRNA and their biogenesis-related genes, increasing their potential mRNA targets. Infliximab reversed those effects. Transfections with pre-miRNA-223, -126 and -148a specifically modulated genes regulating inflammation, survival and migration whereas DICER depletion influenced the inflammatory profile of neutrophils. Taken together RA-neutrophils exhibited a global low abundance of miRNA induced by autoantibodies and inflammatory markers, which potentially contributed to their pathogenic activation. miRNA biogenesis was significantly impaired in RAneutrophils and further associated with a greater downregulation of miRNA mainly related to migration and inflammation in synovial fluid neutrophils. Finally, anti-TNF-a and anti-interleukin-6 receptor treatments can modulate miRNA levels in the neutrophils, minimizing their inflammatory profile.

Our results show that the metabolic disturbances associated with RA depend on the degree of inflammation and identify inflammation of adipose tissue as the initial target leading to IR and the associated molecular disorders of carbohydrate and lipid homeostasis. Thus, we anticipate that therapeutic strategies based on tighter control of inflammation and flares could provide promising approaches to normalize and/or prevent metabolic alterations associated with RA.

To evaluate quality of life (QoL) in patients with axial spondyloarthritis (axSpA) and its association with disease activity, functionality, structural damage, and spinal mobility, using patient-reported outcomes. This was an observational, cross-sectional, and single-center study in which 100 consecutive patients with axSpA were included. We obtained from all patients' sociodemographic data and values related to disease activity, functionality, structural damage, mobility, and quality of life. The Ankylosing Spondylitis Quality of Life Questionnaire (ASQoL) was considered as the primary outcome. Pearson r statistic, Student's T test, and univariate and multivariate linear regressions were performed to relate ASQoL with the studied covariates. Mean ASQoL score in all patients was 4.02 ± 2.81, with statistically significant differences between male and female (3.61 ± 2.80 vs. 4.83 ± 2.70). Patients with high disease activity (measured by the ASAS-endorsed Disease Activity Score, ASDAS > 2.1) showed higher mean score in ASQoL than those with low disease activity (ASDAS ≤ 2.1) (3.21 ± 0.74 vs. 1.43 ± 0.43, p < 0.001). ASQoL presented a significant linear correlation with BASDAI, BASFI, and ASDAS (r > 0.60). However, disease duration was not significantly correlated with ASQoL. Finally, the 68.9% of the ASQoL variability (R = 0.689) was determined by BASDAI, BASFI, and mSASSS, presenting mSASSS a negative regression coefficient (- 0.035). In our study, the impairment of QoL was mainly associated with disease activity (BASDAI) and worsening of functionality (BASFI). However, there is an inverse relationship between the worsening of QoL and structural damage. In addition, disease duration does not seem to influence the patient's welfare.

No abstract

BackgroundSeveral measurements are often used in daily clinical practice in the assessment of Ankylosing Spondylitis (AS) patients. The Assessment in SpondyloArthiritis International Society (ASAS) recommend in its core set: chest expansion modified Schöber test, Occiput to wall distance, lateral lumbar flexion, cervical rotation and The Bath Ankylosing Spondylitis Metrology Index (BASMI). BASMI also includes five measurements, some of them recommended by ASAS. Three versions of BASMI have been published with different scales and intervals for each component of the index. Though studies about reliability of these measurements are needed. The aim of this study was to analyze inter-rater reliability of recommended spinal mobility measures in AS.MethodsWe examined reproducibility of spinal mobility measurements on 33 AS patients performed by two experienced rheumatologists in the same day. Descriptive statistics, Intraclass Correlation Coefficients (ICC), and Smallest Detectable Difference (SDD) using the Bland-Altman criteria were obtained for all the measurements.ResultsChest expansion showed the lowest value of ICC (0.66) and occiput-wall the highest (0.97). SDD was 2.43 units for BASMI2 and 1.27 units for BASMI10.ConclusionsReliability according to ICC was moderate to high in all measurements. BASMI10, instead BASMI2, must be used: measurements used to calculate are the same but there is better reliability. Inter-rater variation, expressed as SDD, must be taken in account: smaller improvements do not demonstrate the efficacy of treatment because they can be due to experimental error and not to the treatment itself.