Both baseline clinical factors and genetic polymorphisms influence the development of severe functional status in ankylosing spondylitis

Functional severity in ankylosing spondylitis (AS) patients is variable and difficult to predict early. The aim of our study was to assess whether a combination of baseline clinical factors and genetic markers may predict the development of severe functional status in AS. We performed a cross-sectional association study on AS patients included in the Spanish National Registry of Spondyloarthropathies-REGISPONSER. Bath Ankylosing Spondylitis Functional Index (BASFI) was standardized by adjusting for disease duration since the first symptoms (BASFI/t). We considered as severe functional status the values of BASFI/t in the top of the 60th (p60), 65th (p65), 70th (p70), and 75th (p75) percentile. We selected 384 single nucleotide polymorphisms (SNPs) distributed in 190 genes to be analyzed. The study cohort included 456 patients with mean age 50.8(±10.5) years and with mean disease duration since first symptoms 24.7 (±10.1) years. Older age at disease onset and neck pain at baseline showed statistical significant association with severe BASFI/t. Polymorphisms associated in the allele frequencies test with severe BASFI/t in all classifications were: rs2542151 (p60 [P =.04], p65 [P =.04], p70 [P =.001] and p75 [P =.001]) and rs2254441 (p60 [P =.004], p65 [P =.02], p70 [P =.01] and p75 [P<.001]). Genotype association, after adjustment for covariates, found an association in three of the four patients' classifications for rs2542151 and in two of the classifications for rs2254441.Forward logistic regression did not identify any model with a good predictive power for severe functional development. In our study we identified clinical factors and 24 polymorphisms associated with development of severe functional status in AS patients. Validation of these results in other cohorts is requiredThis work was supported by the Ministerio de Ciencia e Innovación of Spain [Proyect PSE-01000-2006-1] and by Progenika Biopharma S.

Exploring the unifying concept of Spondyloarthritis: a latent class analysis of the REGISPONSER registry

ObjectivesThe aim of our study is to identify the potential distinct phenotypes within a broad Spondyloarthritis (SpA) population.MethodsWe conducted a cross-sectional study using the REGISPONSER registry with data from 31 specialist centres in Spain including patients with SpA who fulfilled the European Spondyloarthropathy Study Group (ESSG) criteria. A latent class analysis (LCA) was performed to identify the latent classes underlying SpA according to a set of predefined clinical and radiographic features, independently of expert opinion.ResultsIn a population of 2319 SpA patients, a 5 classes LCA model yielded the best fit. Classes named ‘axial with spine involvement’ and ‘axial with isolated SIJ involvement” show a primarily axial SpA phenotype defined by inflammatory back pain and high HLA-B27 prevalence. Patients in class ‘axial + peripheral’ show similar distribution of manifest variables to previous classes but also have a higher likelihood of peripheral involvement (peripheral arthritis/dactylitis) and enthesitis, therefore representing a mixed (axial and peripheral) subtype. Classes ‘Peripheral + psoriasis’ and ‘Axial + peripheral + psoriasis’ are indicative of peripheral SpA (and/or PsA) with high likelihood of psoriasis, peripheral involvement, dactylitis, nail disease, and low HLA-B27 prevalence, while class ‘Axial + peripheral + psoriasis’ also exhibits increased probability of axial involvement both clinically and radiologically.ConclusionThe identification of 5 latent classes in the REGISPONSER registry with significant overlap between axial and peripheral phenotypes is concordant with a unifying concept of SpA. Psoriasis and related features (nail disease and dactylitis) influence the phenotype of both axial and peripheral manifestations.<br/

Effects of Biological Therapies on Molecular Features of Rheumatoid Arthritis

Rheumatoid arthritis (RA) is an autoimmune and chronic inflammatory disease primarily affecting the joints, and closely related to specific autoantibodies that mostly target modified self-epitopes. Relevant findings in the field of RA pathogenesis have been described. In particular, new insights come from studies on synovial fibroblasts and cells belonging to the innate and adaptive immune system, which documented the aberrant production of inflammatory mediators, oxidative stress and NETosis, along with relevant alterations of the genome and on the regulatory epigenetic mechanisms. In recent years, the advances in the understanding of RA pathogenesis by identifying key cells and cytokines allowed the development of new targeted disease-modifying antirheumatic drugs (DMARDs). These drugs considerably improved treatment outcomes for the majority of patients. Moreover, numerous studies demonstrated that the pharmacological therapy with biologic DMARDs (bDMARDs) promotes, in parallel to their clinical efficacy, significant improvement in all these altered molecular mechanisms. Thus, continuous updating of the knowledge of molecular processes associated with the pathogenesis of RA, and on the specific effects of bDMARDs in the correction of their dysregulation, are essential in the early and correct approach to the treatment of this complex autoimmune disorder. The present review details basic mechanisms related to the physiopathology of RA, along with the core mechanisms of response to bDMARDs

Expression of DDX11 and DNM1L at the 12p11 Locus Modulates Systemic Lupus Erythematosus Susceptibility

This study employed genetic and functional analyses using OASIS meta-analysis of multiple existing GWAS and gene-expression datasets to identify novel SLE genes. Methods: Four hundred and ten genes were mapped using SNIPPER to 30 SLE GWAS loci and investigated for expression in three SLE GEO-datasets and the Cordoba GSE50395-dataset. Blood eQTL for significant SNPs in SLE loci and STRING for functional pathways of differentially expressed genes were used. Confirmatory qPCR on SLE monocytes was performed. The entire 12p11 locus was investigated for genetic association using two additional GWAS. Expression of 150 genes at this locus was assessed. Based on this significance, qPCRs for DNM1L and KRAS were performed. Results: Fifty genes were differentially expressed in at least two SLE GEO-datasets, with all probes directionally aligned. DDX11, an RNA helicase involved in genome stability, was downregulated in both GEO and Cordoba datasets. The most significant SNP, rs3741869 in OASIS locus 12p11.21, containing DDX11, was a cis-eQTL regulating DDX11 expression. DDX11 was found repressed. The entire 12p11 locus showed three association peaks. Gene expression in GEO datasets identified DNM1L and KRAS, besides DDX11. Confirmatory qPCR validated DNM1L as an SLE susceptibility gene. DDX11, DNM1L and KRAS interact with each other and multiple known SLE genes including STAT1/STAT4 and major components of IFN-dependent gene expression, and are responsible for signal transduction of cytokines, hormones, and growth-factors, deregulation of which is involved in SLE-development. Conclusion: A genomic convergence approach with OASIS analysis of multiple GWAS and expression datasets identified DDX11 and DNM1L as novel SLE-genes, the expression of which is altered in monocytes from SLE patients. This study lays the foundation for understanding the pathogenic involvement of DDX11 and DNM1L in SLE by identifying them using a systems-biology approach, while the 12p11 locus harboring these genes was previously missed by four independent GWAS

Assessment of Subclinical Psychotic Symptoms in Patients with Rheumatoid Arthritis and Spondyloarthritis

Inflammatory and autoimmune processes have been associated with the onset of depressive and psychotic symptoms. Rheumatoid arthritis (RA) and spondyloarthritis (SpA) are rheumatic diseases with an inflammatory etiology. A high prevalence of depressive and anxiety-related comorbidity has been reported for both diseases, with no evidence of a greater prevalence of psychosis. The objective of the present study was to evaluate for the first time subclinical psychotic symptoms in patients with RA and SpA. This is a cross-sectional, single-center study including RA and SpA patients, as well as healthy controls. Abnormal psychotic experiences (positive, negative, and depressive symptoms) were evaluated using the Community Assessment of Psychic Experiences (CAPE-42). Functional capacity was evaluated using the Short-Form Health Survey SF-12. We compared the CAPE and SF-12 scores between the three groups. We recruited 385 individuals: 218 with RA, 100 with SpA, and 67 healthy controls. According to the CAPE scale, the frequency of subclinical psychotic symptoms was greater in patients than in healthy controls (RA, 1.90 vs. 1.63, p < 0.001; SpA, 1.88 vs. 1.63, p = 0.001). Distress was also greater in patients than in controls owing to the presence of symptoms. No differences were observed between the three groups for the mental dimension scores in the SF-12 Health Survey (43.75 in RA, 45.54 in SpA, and 43.19 in healthy controls). Our findings point to a greater prevalence of subclinical psychotic symptoms in patients with RA and patients with SpA than in the general population. The results suggest an association between inflammation and depression/subclinical psychotic symptoms

Sanitary education for students of children teachers directed to dealing with the allergic children at the school

La alergia en edad pediátrica es un problema de salud pública emergente y a su vez complejo de abordar. A pesar de esto, apenas hay protocolos de identificación de alumnos alérgicos y tampoco se incluyen en los planes docentes de los futuros profesores aspectos relacionados con la alergia infantil y del adolescente. Dado que los niños pasan una importante parte de su vida en la escuela, con éste proyecto se pretende formar a estudiantes de Grado en Educación Infantil y Grado en Educación Primaria en nociones básicas sobre qué es y qué supone una alergia alimentaria y/ó un asma, en el reconocimiento de los primeros síntomas de una reacción alérgica y en cómo actuar cuando ésta se ha producido. Se propuso a los participantes (todos alumnos de Magisterio) que rellenaran de forma anónima un cuestionario donde se preguntaba acerca del manejo del niño alérgico en la escuela, mediante 44 preguntas. A continuación se llevarían a cabo varias sesiones formativas y un mes despúes de la formación se volvería a pasar el mismo cuestionario, para valorar la evolución del conocimiento de los alumnos en el tema alergológico. Con el presente trabajo se muestra que los futuros maestros presentan unos conocimientos escasos acerca de la Alergología. Sería conveniente plantear programas de educación sanitaria de patologías cada vez más prevalentes en la población general y especialmente de las que se manifiestan en niños, ya que como se demuestra en este trabajo, la realización de seminarios informativos mejora de forma significativa el conocimiento sobre dicho tema de los futuros docentes en la escuela.Allergic diseases in children are an emergent issue of public health difficult to deal with. nevertheless, there barely are available protocols to identify allergic pupils neither some chapters relative to allergy in childhood and adolescence are included in academic programs of future teachers. Since children spend much time at the school, this project aims to give basic education to future children teachers, directed to know which both asthma and food allergy are, how identify early allergic symptoms, and what to do in front of an allergic episode. A group of students of university school for children teachers were asked to anonymously fill in a survey about the allergic children at the school, including 44 items. After that, an allergist carried out an educational program of basic allergy directed to the participants, and one month later, the same survey was offered to them in order to size the evolution of the knowledge. Future children teachers show a low profile of knowledge about allergy. It would be adequate to give them sanitary education about highly prevalent diseases, particularly in the case of pediatric diseases. This project has demonstrated the high value of educational seminars to improve the aimed results

Patients with Axial Spondyloarthritis Show an Altered Flexion/Relaxation Phenomenon

Axial spondyloarthritis (axSpA) is a chronic rheumatic disease characterized by the presence of inflammatory back pain. In patients with chronic low back pain, the lumbar flexion relaxation phenomenon measured by surface electromyography (sEMG) differs from that in healthy individuals. However, sEMG activity in axSpA patients has not been studied. The purpose of this study was to analyze the flexion relaxation phenomenon in axSpA patients. A study evaluating 39 axSpA patients and 35 healthy controls was conducted. sEMG activity at the erector spinae muscles was measured during lumbar full flexion movements. sEMG activity was compared between axSpA patients and the controls, as well as between active (BASDAI ≥ 4) and non-active (BASDAI 0.8 for 1/FRR) and criterion validity. ROC analysis showed good discriminant validity for axSpA patients (AUC = 0.835) vs. the control group using 1/FRR. An abnormal flexion/relaxation phenomenon exists in axSpA patients compared with controls. sEMG could be an additional objective tool in the evaluation of patient function and disease activity status

Subclinical Atherosclerosis Measure by Carotid Ultrasound and Inflammatory Activity in Patients with Rheumatoid Arthritis and Spondylarthritis

Objective: To compare the effect of inflammation on subclinical atherosclerosis using carotid ultrasound in patients with rheumatoid arthritis (RA) and spondyloarthritis (SpA). Methods: Cross-sectional study including 347 participants (148 RA, 159 SpA, and 40 controls). We measured the carotid intima media thickness (cIMT) and detection of atheromatous plaques using carotid ultrasound. We recorded disease activity (DAS28-CRP/ASDAS-CRP) and traditional cardiovascular risk factors. We performed descriptive, bivariate, and linear multivariate analyses (dependent variable: cIMT) to evaluate the influence of diagnosis on cIMT in all patients. Two additional multivariate analyses were performed by stratifying patients according to their inflammatory activity. Results: cIMT correlated with the mean CRP during the previous 5 years in RA, but not with CRP at the cut-off date. We did not find such differences in patients with SpA. The first multivariate model revealed that increased cIMT was more common in patients with RA than in those with SpA (β coefficient, 0.045; 95% confidence interval (95% CI), 0.0002–0.09; p = 0.048) after adjusting for age, sex, disease course, and differential cardiovascular risk factors (arterial hypertension, smoking, statins, and corticosteroids). The second model revealed no differences in cIMT between the 2 groups of patients classified as remission–low activity (β coefficient, 0.020; 95% CI, −0.03 to 0.080; p = 0.500). However, when only patients with moderate–high disease activity were analysed, the cIMT was 0.112 mm greater in those with RA (95% CI, 0.013–0.212; p = 0.026) than in those with SpA after adjusting for the same variables. Conclusions: Subclinical atherosclerosis measured by carotid ultrasound in patients with RA and SpA is comparable when the disease is well controlled. However, when patients have moderate–high disease activity, cIMT is greater in patients with RA than in those with SpA after adjusting for age, sex, disease course, and cardiovascular risk factors. Our results point to greater involvement of disease activity in subclinical atherosclerosis in patients with RA than in those with SpA

Prevalence and Associated Factors of Low Bone Mineral Density in the Femoral Neck and Total Hip in Axial Spondyloarthritis: Data from the CASTRO Cohort

Studies on osteoporosis in axial spondyloarthritis (axSpA) have focused on the lumbar segment, and few studies have assessed bone mineral density (BMD) in the hip and femoral neck in these patients. The aim of this study was to evaluate the prevalence of low BMD and osteopenia in the total hip or femoral neck and the factors associated with these conditions in axSpA patients. This was a single-centre, observational, cross-sectional study among consecutive patients with axSpA according to the ASAS criteria from the CASTRO registry. All patients underwent total hip and femoral neck DXA BMD measurements. Low BMD was defined as a Z-score less than −1, and osteopenia was defined as a T-score less than −1. Multivariate logistic and generalised linear regressions were used to evaluate factors independently associated with low BMD and osteopenia in the hip or femoral neck and those associated with variability in BMD, respectively. A total of 117 patients were included, among which 30.8% were female and the mean age was 45 years. A total of 36.0% of patients had low BMD (28.1% in the total hip and 27.4% in the femoral neck), and 56.0% of patients had osteopenia (44.7% in the total hip and 53.8% in the femoral neck). A multivariate logistic regression showed that age, radiographic sacroiliitis and ASAS-HI were independently associated with low BMD in the total hip or femoral neck. Factors that were independently associated with osteopenia were Body Mass Index, disease duration, radiographic sacroiliitis and ASAS-HI. In conclusion, 36% of the patients with axSpA had low BMD in the total hip or femoral neck. A younger age and radiographic sacroiliitis were the most important factors associated with decreased BMD

Measuring Spinal Mobility Using an Inertial Measurement Unit System: A Validation Study in Axial Spondyloarthritis

Portable inertial measurement units (IMUs) are beginning to be used in human motion analysis. These devices can be useful for the evaluation of spinal mobility in individuals with axial spondyloarthritis (axSpA). The objectives of this study were to assess (a) concurrent criterion validity in individuals with axSpA by comparing spinal mobility measured by an IMU sensor-based system vs. optical motion capture as the reference standard; (b) discriminant validity comparing mobility with healthy volunteers; (c) construct validity by comparing mobility results with relevant outcome measures. A total of 70 participants with axSpA and 20 healthy controls were included. Individuals with axSpA completed function and activity questionnaires, and their mobility was measured using conventional metrology for axSpA, an optical motion capture system, and an IMU sensor-based system. The UCOASMI, a metrology index based on measures obtained by motion capture, and the IUCOASMI, the same index using IMU measures, were also calculated. Descriptive and inferential analyses were conducted to show the relationships between outcome measures. There was excellent agreement (ICC > 0.90) between both systems and a significant correlation between the IUCOASMI and conventional metrology (r = 0.91), activity (r = 0.40), function (r = 0.62), quality of life (r = 0.55) and structural change (r = 0.76). This study demonstrates the validity of an IMU system to evaluate spinal mobility in axSpA. These systems are more feasible than optical motion capture systems, and they could be useful in clinical practice