Reduced expression of miRNAs as potential biomarkers in axial spondyloarthritis.

OBJECTIVE: This study aimed to investigate the value of miR-29a-3p, miR-27a, miR126-3p, miR-146a-5p, miR-625-3p, miR-130a, miR-32, miR-218, miR-131, and miR5196 in the diagnosis of axial spondyloarthritis and to determine whether there is a difference in miRNA expression levels between radiographic axial spondyloarthritis and non-radiographic axial spondyloarthritis, as well as the relationship between miRNA expression levels, disease activity, and uveitis history. METHODS: This study included 50 patients with axial spondyloarthritis (25 with radiographic axial spondyloarthritis and 25 with non-radiographic axial spondyloarthritis) and 25 healthy individuals. The fold change of miRNA expression for each miRNA was calculated using the 2-ΔΔCt method. RESULTS: The expression of all miRNAs except miR-130a was downregulated in axial spondyloarthritis patients (miR-27a: fold regulation: -11.21, p<0.001; miR-29a-3p: fold regulation: -2.63, p<0.001; miR-32: fold regulation: -2.94, p=0.002; miR-126-3p: fold regulation -10.94, p<0.001; miR-132: fold regulation: -2.18, p<0.001; miR-146-5p: fold regulation: -9.78, p<0.001; miR-218: fold regulation: -2.65, p<0.001; miR-625-3p: fold regulation: -2.01, p=0.001; miR-5196-3p: fold regulation: -7.04, p<0.001). The expression levels of these miRNAs did not differ significantly between non-radiographic axial spondyloarthritis and radiographic axial spondyloarthritis patients (p>0.05 for all). CONCLUSION: Particularly, miR-27a, miR-126-3p, miR-146-5p, and miR-5196-3p were found to be substantially downregulated in both non-radiographic axial spondyloarthritis and radiographic axial spondyloarthritis patients, suggesting their potential as diagnostic biomarkers for axial spondyloarthritis.

Presentation of enthesitis-related arthritis and juvenile-onset spondyloarthritis: a cross-sectional study in a pediatric and adult clinic.

BACKGROUND: Juvenile idiopathic arthritis (JIA) comprises a whole spectrum of chronic arthritis starting before 16 years of age. The study aims to explore the clinical and demographic descriptors, treatment, and disease progression of enthesitis-related arthritis (ERA) in comparison with juvenile-onset spondyloarthritis (SpA). METHODS: Cross-sectional analysis of consecutive patients in two dedicated clinics, with a single visit and retrospective case-notes review. Arthritis, enthesitis and sacroiliitis were evaluated by scoring disease activity and damage. Continuous variables were reported by median, interquartile range; categorical variables were reported by the frequency comparison of the two groups. RESULTS: Thirty-three cases were included, being 23 (69.7%) with ERA. The median age at diagnosis was 12.5 y (SpA) vs. 9 y (ERA) (p < 0.01); the time from symptom onset to diagnosis was 5.5 y (SpA) vs. 1.5 y (ERA) (p < 0.03). In both groups, the predominant presentation was a single joint or < 5 lower limb joints and asymmetric involvement, with a high frequency of enthesitis. There was a higher frequency of mid-tarsal and ankle synovitis in the ERA group and hip involvement in those with SpA. The comparison of the frequency of spine symptoms at presentation, 30% SpA vs. 21.7% ERA (p = 0.7), was not significant, and radiographic progression to spinal involvement occurred in 43.5% of ERA patients. The median time for spinal progression and age at onset was 2.2 and 12 y for ERA, and 4 and 16.5 y for SpA, respectively. Activity and damage scores were not significantly different between the groups. Treatment comparison resulted in 91.3% of ERA and 100% SpA being treated, predominantly with NSAIDs in both groups, followed by DMARDs and biologics, with a higher frequency of biologics in SpA. CONCLUSION: The main differences were the late diagnoses of SpA, and the hip and spine involvement, with higher frequency of biologic treatment in juvenile-onset SpA compared to ERA.

Differences between radiographic and non-radiographic axial spondyloarthritis patients in a Mexican cohort.

To compare the demographic, clinical, and laboratory characteristics, disease onset, and clinical features of radiographic axial Spondyloarthritis (r-axSpA) and non-radiographic axial Spondyloarthritis (nr-axSpA) patients. All patients who attended outpatient spondylarthritis (SpA) clinics at Hospital General de Mexico and the Instituto Nacional de la Nutrición from 1998 to 2005 and met the rheumatologist diagnostic criteria for SpA were selected. Then the SpA patients were classified by European Spondyloarthropathy Study Group criteria (ESSG). We selected SpA patients with axial presentation as axial SpA (axSpA), and they were classified as r-axSpA if they met modified New York (mNY) criteria for sacroiliitis and as nr-axSpA if they did not meet mNY criteria; to compared clinical, demographic, and laboratory test between the subgroups. It included 148 SpA patients; 55 (37.2%) patients had r-axSpA, and 70 (47.3%) had nr-axSpA. The nr-axSpA patients had a lower proportion of males (58.6% vs 78.2%, P < 0.05), lower HLA-B27 frequency (54.3%. vs. 92.7%, P < 0.05), were older at disease onset (21 vs 16 years; P < 0.01) and had a higher frequency of infections at disease onset (9.1% vs 32.9, P < 0.05) than r-axSpA. BASFI (2.9 vs 4.8; P < 0.0001), Dougados functional index (7 vs. 14; P < 0.05), and BASDAI (4.1 vs. 5.2; P < 0.001) were lower in patients with nr-axSpA than r-axSpA, respectively. The factors that most influenced the presentation of r-axSpA were history of uveitis (OR 14, 95% CI 2.3-85), HLA-B27 (OR 7.97, 95% CI, 2.96-122), male sex (OR 6.16, 95% CI, 1.47-25.7), axial enthesopathy count (OR 1.17 95% CI, 1.03-1.33). This study provides insight into the differences between nr-axSpA and r-axSpA in Mexico. Patients with r-axSpA were mainly male, with a younger presentation age, a higher prevalence of HLA-B27, more history of uveitis, fewer episodes of dactylitis, more axial enthesopathy, and higher disease activity than nr-axSpA.

An immunocompetent host with blood-disseminated Aspergillus versicolor spondylitis: a case report and literature review.

Blood-disseminated Aspergillus spondylitis in immunocompetent individuals is rare. The clinical, imaging, and pathological manifestations of this condition are not specific. Therefore, this disease is prone to misdiagnosis and a missed diagnosis. Systemic antifungal therapy is the main treatment for Aspergillus spondylitis. We report a case of blood-disseminated Aspergillus versicolor spondylitis in a patient with normal immune function. The first antifungal treatment lasted for 4 months, but Aspergillus spondylitis recurred a few months later. A second antifungal treatment course was initiated for at least 1 year, and follow-up has been ongoing. Currently, there has been no recurrence.

Diagnostic accuracy in axial spondyloarthritis: a systematic evaluation of the role of clinical information in the interpretation of sacroiliac joint imaging.

OBJECTIVES: Radiography and MRI of the sacroiliac joints (SIJ) are relevant for the diagnosis and classification of patients with axial spondyloarthritis (axSpA). This study aimed to evaluate the impact of clinical information (CI) on the accuracy of imaging interpretation. METHODS: Out of 109 patients referred because of suspicion of axSpA with complete imaging sets (radiographs and MRI of SIJ), 61 were diagnosed with axSpA (56%). Images were independently evaluated by three radiologists in four consecutive reading campaigns: radiographs and radiographs+MRI without and with CI including demographic data, SpA features, physical activity and pregnancy. Radiographs were scored according to the modified New York criteria, and MRIs for inflammatory and structural changes compatible with axSpA (yes/no). The clinical diagnosis was taken as reference standard. The compatibility of imaging findings with a diagnosis of axSpA (precision) before and after the provision of CI and radiologists' confidence with their findings (0-10) were evaluated. RESULTS: The precision of radiographs evaluation without versus with CI increased from 70% to 78% (p=0.008), and for radiographs+MRI from 81% to 82% (p=1.0), respectively. For CR alone, the sensitivity and specificity of radiologic findings were 51% and 94% without and 60% and 100% with CI, while, for radiographs+MRI, they were 74% and 90% vs 71% and 98%, respectively. The diagnostic confidence of radiologists increased from 5.2±1.9 to 6.0±1.7 with CI for radiographs, and from 6.7±1.6 to 7.2±1.6 for radiographs+MRI, respectively. CONCLUSION: The precision, specificity and diagnostic confidence of radiologic evaluation increased when CI was provided.

Frequency and the effects of spondyloarthritis-spectrum disorders on the clinical course and management of Takayasu arteritis: an observational retrospective study.

OBJECTIVES: Extravascular findings of Takayasu arteritis (TAK) often share features with the spondyloarthritis (SpA) spectrum of disorders. However, the characteristics of this overlap and its effect on the vascular manifestations of TAK are not fully known. Therefore, we aimed to investigate the frequency of SpA-related features in TAK patients. MATERIAL AND METHODS: In this observational retrospective study, 350 patients with TAK classified according to ACR 1990 criteria, from 12 tertiary rheumatology clinics, were included and evaluated for the presence of axSpA, IBD, or psoriasis. Demographic, clinical features, angiographic involvement patterns, disease activity, and treatments of TAK patients with or without SpA were analyzed. RESULTS: Mean age was 45.5 ± 13.6 years and mean follow-up period was 76.1 ± 65.9 months. Among 350 patients, 31 (8.8%) had at least one additional disease from the SpA spectrum, 8 had IBD, 8 had psoriasis, and 20 had features of axSpA. In the TAK-SpA group, TAK had significantly earlier disease onset, compared to TAK-without-SpA (p = 0.041). SpA-related symptoms generally preceded TAK symptoms. Biological treatments, mostly for active vasculitis, were higher in the TAK-SpA group (70.9%) compared to TAK-without-SpA (27.9%) (p < 0.001). Vascular involvements were similar in both. CONCLUSION: Our study confirmed that diseases in the SpA spectrum are not rare in TAK. Vascular symptoms appeared earlier in such patients, and more aggressive therapy with biological agents was required in the TAK-SpA group, suggesting an association between TAK and SpA spectrum. Key Points • The pathogenesis of Takayasu arteritis is mediated by an MHC class I alelle (HLA-B*52), similar to spondyloarthritis-disorders. • Extravascular findings of Takayasu arteritis are in the spectrum of spondyloarthritis disease. • This frequent coexistence between Takayasu arteritis and spondyloarthritic disorders suggests a relationship rather than a coincidence.

[Diagnosis and classification of axial spondyloarthritis (axSpA) - the current status]. / Diagnostik und Klassifikation der axialen Spondyloarthritis (axSpA) ­ der aktuelle Stand.

Axial spondyloarthritis (axSpA) is an inflammatory rheumatic disease typically characterized by inflammatory back pain (IBP). The term axSpA has largely replaced the long-used term ankylosing spondylitis (AS). IBP is caused by inflammation in the axial skeleton, with the sacroiliac joints (SIJ) being particularly frequently affected initially. The spine is usually added in later stages, which is then increasingly characterized structurally by the formation of new bone. The overall concept of spondyloarthritis includes other disease manifestations such as uveitis, psoriasis and colitis and comorbidities such as cardiovascular disease and osteoporosis.The ASAS classification criteria for axSpA, in place since 2009, have replaced the 1984 modified New York criteria. In the former, in addition to conventional X-rays, changes in the SIJ detected by magnetic resonance imaging (MRI) and also the detection of HLA B27 have, for the first time, played a role. It is important to note that these are not diagnostic criteria, as they do not exist. This paper outlines 10 points that should be considered when making a diagnosis.

The prevalence of chronic obstructive pulmonary disease in patients with spondyloarthritis compared to the general population in the southernmost region of Sweden: a case-control study.

Spondyloarthritis (SpA) has been associated with comorbidities, e.g., cardiovascular disease. However, little is known about the relation between SpA and chronic obstructive pulmonary disease (COPD). The aim of the study was to compare the prevalence of COPD in SpA to the general population. Patients with prevalent SpA in Skåne, Sweden, on December 31, 2018, were identified based on diagnostic codes in a regional register on primary care, secondary outpatient care and inpatient care. Population-based controls (5 per SpA case) were matched for age, sex and municipality. The base case definition for COPD required at least two prior visits with a registered COPD diagnosis. Stricter definitions included dispensed prescriptions for COPD and a COPD diagnosis made by a specialist in lung medicine. The prevalence of COPD in patients with SpA and controls, overall and stratified by sex and age, and the corresponding prevalence ratios, were estimated. A total of 3571 patients with SpA (51% male, mean age 53 years) were compared to 17,855 matched controls. The prevalence of COPD in patients with SpA was 37.8/1000, with a prevalence ratio compared to controls of 1.03 (95% CI 0.85-1.24). There were no significant differences in COPD prevalence between patients with SpA and controls in men or women, in any of the age groups, or in analyses using stricter definitions of COPD. In this regional study including data from primary care, the prevalence of COPD was not increased in patients with SpA compared to the background population.

Association of clinical response criteria and disease activity levels with axial spondyloarthritis core domains: results from two phase 3 randomised studies, BE MOBILE 1 and 2.

OBJECTIVE: To assess how achievement of increasingly stringent clinical response criteria and disease activity states at week 52 translate into changes in core domains in patients with non-radiographic (nr-) and radiographic (r-) axial spondyloarthritis (axSpA). METHODS: Patients in BE MOBILE 1 and 2 achieving different levels of response or disease activity (Assessment of SpondyloArthritis International Society (ASAS) and Ankylosing Spondylitis Disease Activity Score (ASDAS) response criteria, Bath Ankylosing Spondylitis Disease Activity Index (BASDAI50)) at week 52 were pooled, regardless of treatment arm. Associations between achievement of these endpoints and change from baseline (CfB) in patient-reported outcomes (PROs) measuring core axSpA domains, including pain, fatigue, physical function, overall functioning and health, and work and employment, were assessed. RESULTS: Achievement of increasingly stringent clinical efficacy endpoints at week 52 was generally associated with sequentially greater improvements from baseline in all PROs. Patients with nr-axSpA achieving ASAS40 demonstrated greater improvements (CfB) than patients who did not achieve ASAS40 but did achieve ASAS20, in total spinal pain (-5.3 vs -2.8, respectively), Functional Assessment of Chronic Illness-Fatigue subscale (12.7 vs 6.7), Bath Ankylosing Spondylitis Function Index (-3.9 vs -1.8), European Quality of Life 5-Dimension 3-Level Version (0.30 vs 0.16), Work Productivity and Activity Impairment-axSpA presenteeism (-35.4 vs -15.9), overall work impairment (-36.5 vs -12.9), activity impairment (-39.0 vs -21.0) and sleep (9.0 vs 3.9). Results were similar for ASDAS and BASDAI50. Similar amplitudes of improvement were observed between patients with nr-axSpA and r-axSpA. CONCLUSIONS: Patients treated with bimekizumab across the full axSpA disease spectrum, who achieved increasingly stringent clinical response criteria and lower disease activity at week 52, reported larger improvements in core axSpA domains.

Tuberculosis and Nontuberculous Mycobacterial Infections in Patients with Spondyloarthritis: A Population-Based Study.

Background and Objectives: Tuberculosis is caused by Mycobacterium tuberculosis (MTB), while nontuberculous mycobacteria (NTM) encompass a group of mycobacterial species that are distinct from the MTB complex and leprae. Spondyloarthritis (SpA) is a group of chronic inflammatory diseases with shared clinical characteristics and is treated with biological agents; however, their use may elevate the risk of MTB and NTM infections. This study aimed to compare the incidence and risk of MTB and NTM infections in patients with SpA, including ankylosing spondylitis (AS) and psoriatic arthritis (PsA), using a population-based approach. Materials and Methods: This study included 2333 patients with SpA and 9332 age- and sex-matched controls from the Korea National Health Insurance Service-National Sample Cohort database from 2002 to 2019. The patients were identified using the International Classification of Diseases-10 codes for AS, PsA, MTB, and NTM. Results: The results showed that a negligible percentage of patients with SpA developed NTM (0.002%) and MTB (0.016%), with no significant difference in the incidence rate ratio (IRR) compared to controls. Among patients with SpA treated with biologics, the IRRs for NTM and MTB were 5.66 and 3.069, respectively; however, these were not statistically significant. No cases of NTM or MTB infection were reported in female patients with SpA treated with biologics. In both the SpA patient group and the control group, the incidence of MTB was higher in individuals over 60 years old compared to those under 60 years old. Cox proportional hazard analysis revealed a significant adjusted hazard ratio of 1.479 for MTB in patients with SpA after adjusting for age, sex, smoking history, insurance level, and comorbidities. However, this significance was not maintained when biological therapy was further adjusted. Conclusions: Our study indicated that the risks of NTM and MTB infection are not elevated in patients with SpA. Although biological use may potentially increase the risk of MTB infection, it does not lead to a significant increase in incidence rates. Proactive screening for latent tuberculosis and adequate prophylaxis using biologics can effectively manage the risk of NTM and MTB infections.

Prevalence of spondyloarthritis in inflammatory bowel disease according ASAS and ultrassonography and its correlation with plasma calprotectin.

BACKGROUND: Enteropathic spondyloarthritis is underdiagnosed and inflammatory biomarkers and ultrasonography (US) could be useful for screening inflammatory bowel disease (IBD) patients. The objective of this study was to evaluate the prevalence of spondyloarthritis (SpA) in IBD patients, according to the Assessment of SpondyloArthritis International Society (ASAS) criteria and the correlation of results of US of entheses and joints with plasma calprotectin levels. METHODS: This was an observational cross-sectional study. Patients from the IBD outpatient clinic of a reference center were evaluated according to ASAS criteria classification, results of US of entheses and joints, and inflammatory biomarker measurements (erythrocyte sedimentation rates, C-reactive protein levels, fecal and plasma calprotectin levels). A p value lower than 0.05 was considered significant. RESULTS: A total of 30.5% of the studied sample (n = 118) of patients with IBD presented at least one inflammatory musculoskeletal manifestation. The overall prevalence of enteropathic SpA was 13.55%, with 10.16% axial SpA and 4.23% peripheral SpA according to the ASAS criteria. A total of 42.1% of patients had an MASEI score greater than 18, 35.2% had synovitis, and 14.7% had tenosynovitis on US, increasing the frequency of diagnosis of enteropathic SpA to 22.8%. Plasma calprotectin levels were similar to those in healthy controls, and correlated only with the fecal calprotectin level (p 0.041). CONCLUSIONS: A total of 13.5% of patients met the criteria in accordance with the ASAS criteria for enteropathic SpA, which increased to 22.8% with the addition of US. The prevalence of enthesitis, synovitis and tenosynovitis by US of symptomatic joints and entheses were 42%, 35% and 14.7% respectively. Plasma calprotectin was correlated with fecal calprotectin but not with inflammatory biomarkers or US or ASAS criteria.

To be or not to B27 positive: implications for the phenotypes of axial spondyloarthritis outcomes. Data from a large multiracial cohort from the Brazilian Registry of Spondyloarthritis.

BACKGROUND: There is a remarkable variability in the frequency of HLA-B27 positivity in patients with spondyloarthritis (SpA), which may be associated with different clinical presentations worldwide. However, there is a lack of data considering ethnicity and sex on the evaluation of the main clinical and prognostic outcomes in mixed-race populations. The aim of this study was to evaluate the frequency of HLA-B27 and its correlation with disease parameters in a large population of patients from the Brazilian Registry of Spondyloarthritis (RBE). METHODS: The RBE is a multicenter, observational, prospective cohort that enrolled patients with SpA from 46 centers representing all five geographic regions of Brazil. The inclusion criteria were as follow: (1) diagnosis of axSpA by an expert rheumatologist; (2) age ≥18 years; (3) classification according to ASAS axial. The following data were collected via a standardized protocol: demographic data, disease parameters and treatment historical. RESULTS: A total of 1096 patients were included, with 73.4% HLA-B27 positivity and a mean age of 44.4 (±13.2) years. Positive HLA-B27 was significantly associated with male sex, earlier age at disease onset and diagnosis, uveitis, and family history of SpA. Conversely, negative HLA-B27 was associated with psoriasis, higher peripheral involvement and disease activity, worse quality of life and mobility. CONCLUSIONS: Our data showed that HLA-B27 positivity was associated with a classic axSpA pattern quite similar to that of Caucasian axSpA patients around the world. Furthermore, its absence was associated with peripheral manifestations and worse outcomes, suggesting a relevant phenotypic difference in a highly miscegenated population.

[HLA genotypes associated with gastrointestinal symptoms in patients with spondyloarthritis without inflammatory bowel disease]. / Genotipos HLA asociados a síntomas gastrointestinales en pacientes con espondiloartritis sin enfermedad inflamatoria intestinal.

OBJECTIVE: This study aimed to establish the association between HLA-A, B, DR genotypes and gastrointestinal variables in patients with SpA without inflammatory bowel disease (IBD). METHODS: Retrospective study of 91 patients with SpA and 401 healthy controls, with typing by Illumina Sequencing/PacBio and LIFECODES HLA-PCR/SSO multiplex sequencing technology. The presence of gastrointestinal symptoms was evaluated by administering a survey, and those who presented 2 or more symptoms were taken for clinical evaluation by rheumatology and gastroenterology, colonoscopy and histopathological study. (Ethics committee approval). RESULTS: The 59,3% of the patients were men, with a mean age of 43,9±11.4 years; 80,2% were classified as ankylosing spondylitis. 14, 28 and 19 genotypes for the HLA-A*, HLA-B* and HLA-DR* loci were identified in both groups, of which a relationship with gastrointestinal symptoms was identified: A*26, A*29 and B*27 were associated to abdominal pain, DRB1*11 and DRB1*16 with abdominal distention, A*30, B*38, DRB1*13 and DRB1*14 with weight loss, B*40 with diarrhea >4 weeks, and presence of mucus in the stools with A*02 and DRB1*11 (p<0.05). Furthermore, the presence of B*15 had a statistical relationship with intolerance to some food, highlighting the B*27 genotype in relation to grains and dairy products, A*23 with grains, vegetables and meats, and B*49 with vegetables and dairy (p<0.05). Regarding the endoscopic variables, macroscopic changes were found in the ileum mucosa related to A*02, B*48, DRB1*14 and the relationship between B*27 and ulcers at this level should be highlighted. Macroscopic changes in the sigmoid colon with B*48 and the rectum with A*30. In microscopic changes, inflammatory alterations of the ileum are mentioned with genotypes DRB1*07, DRB1*13 and DRB1*14, a genotype that is related to changes in the ileum both endoscopically and histologically (p<0.05). CONCLUSIONS: These findings indicate a potential genetic predisposition related to HLA genotypes that may increase the likelihood of food intolerance, gastrointestinal symptoms, and even visible and microscopic changes, specifically in the ileal tissue. The study highlights the presence of B*27 and other noteworthy HLA class I and class II genes (such as DRB1*14) in the diverse Colombian population.

OBJETIVO: Establecer la asociación entre genotipos HLA-A, B, DR y variables gastrointestinales en pacientes con EspA, sin enfermedad inflamatoria intestinal (EII). MÉTODOS: Estudio retrospectivo de 91 pacientes con EspA y 401 controles sanos, con tipificación por tecnología de secuenciación Illumina Sequencing/PacBio, y LIFECODES HLA-PCR/SSO multiplex. Se evaluó la presencia de síntomas gastrointestinales por aplicación de una encuesta, y, aquellos que presentaran dos o más síntomas, fueron llevados a valoración clínica por reumatología y gastroenterología, colonoscopia y estudio histopatológico. (Aprobación del Comité de Ética, HMC, 2022 - 2020). RESULTADOS: El 59,3% de los pacientes fueron hombres, con edad media de 43,9 ± 11,4 años. El 80,2% se clasificó como espondilitis anquilosante. Se identificaron en ambos grupos 14, 28 y 19 genotipos para los loci HLA-A*, HLA-B* y HLA-DR*, de los cuales se identificó relación con síntomas gastrointestinales: A*26, A*29 y B*27, con dolor abdominal; DRB1*11 y DRB1*16, con distensión abdominal; A*30, B*38, DRB1*13 y DRB1*14, con pérdida de peso; B*40, con diarrea >4 semanas y presencia de moco en las deposiciones con A*2 y DRB1*11 (p<0,05). Además, la presencia de B*15, tuvo relación estadística con intolerancia a algún tipo de alimento, a resaltar el genotipo B*27, en relación con granos y lácteos; A*23 con granos, verduras y carnes; y el B*49, con verduras y lácteos (p<0,05). Frente a las variables endoscópicas, se encontraron cambios macroscópicos en la mucosa de íleon relacionados con A*02, B*48, DRB1*14 y, a destacar, la relación B*27 con úlceras a este nivel. Cambios macroscópicos en colon sigmoides con B*48 y en recto con A*30. En cambios microscópicos, se mencionan alteraciones inflamatorias de íleon con genotipos DRB1*07, DRB1*13 y DRB1*14, genotipos que se relaciona a cambios en íleon tanto endoscópica e histológicamente (p<0,05). CONCLUSIONES: Estos resultados sugieren una posible susceptibilidad genética asociada al HLA, con genotipos que pueden predisponer a intolerancia alimentaria, síntomas gastrointestinales, e incluso, a cambios macroscópicos e histológicos, particularmente en tejido de íleon, entre los cuales está presente el B*27, pero resaltan otros interesantes en HLA clase I, como clase II (DRB1*14), en una población de alto mestizaje como la colombiana.

[Faecal microbiota study reveals specific dysbiosis in spondyloarthritis according to subtype, disease activity and treatment]. / Estudio de microbiota fecal revela disbiosis específica en espondiloartritis, según subtipo, actividad de la enfermedad y tratamiento.

OBJECTIVE: To compare the diversity and composition of the gastrointestinal microbiome of patients with SpA. METHODS: MiSeq sequencing of the V3-V4 region of the 16S ribosomal RNA gene was performed on DNA isolated from stool. Patients with concurrent SpA and IBD were excluded. Differences were assessed for richness and diversity indices by QIIME 2™. Differences between means >0,2% with a p-value<0,05 were assumed significant. Institutional Ethics Committee endorsement. RESULTS: 69 individuals included, 49 with SpA (ankylosing spondylitis-AS 72,9%, psoriatic arthritis-PsA 18,8%, reactive arthritis-ReA 8,3%) 5 positive controls-dysbiosis and 15 controls-eubiosis. Conventional treatment in 42,9%, anti-IL-17 16,3% and anti-TNF 40,8%. By subtype, statistically significant differences in favour of AS were found for the diversity indices. AS vs PsA there was a difference in favour of AS for Clostridium clostridioforme (p=0,002), Gemmiger formicilis (p=0,009), Roseburia inulivorans (p=0,008) and Lachnospira pectinoschiza. AS vs ReA there was a difference in favour of AS for L. pectinoschiza (p=0,009), Ruminococcus callidus (p=0.006), Clostridium ruminantium (p=0.031); G. formicilis (p=0,034). Diversity and richness showed differences in patients with high activity for Simpson's and Pielou's indices. In high activity, lower enrichment of Bacteroides eggerthii (p= 0,0003), C. ruminantium (p= 0,026) and Alistipes putredinis (p=0,035) was found. The number of ASV was higher in the anti-IL-17 vs conventional group (p=0.025) and a trend between anti-IL-17 vs anti-TNF (p=0.09). In anti-TNF there was a lower proportion for C. clostridioforme (p=0.023), G. formicilis (p=0.030) and R. callidus (p= 0.003). In anti IL-17, Alistipes indistinctus (p= 0.012) was decreased. CONCLUSIONS: There are differences in microbial diversity for SpA subtypes. The level of disease activity is plausible to influence the composition of the faecal microbiota. Anti-TNFα treatment may influence the microbiome environment favouring restoration of the gut microbiota, while anti-IL-17 may maintain an inflammatory environment.

OBJETIVO: Comparar la diversidad y composición del microbioma gastrointestinal de pacientes con EspA. MÉTODOS: La secuenciación MiSeq de la región V3-V4 del gen ARN ribosomal 16, se realizó en ADN aislado de heces. Se excluyeron pacientes con EspA y EII simultánea. Se evaluaron diferencias para los índices de riqueza y diversidad por medio de QIIME 2™. Las diferencias entre medias> 0,2%, con un valor de p< 0,05, se asumieron significativas. Aval del Comité de Ética Institucional. RESULTADOS: 69 individuos incluidos, 49 con EspA (espondilitis anquilosante-EA 72,9%, artritis psoriásica-APs 18,8%, artritis reactiva-ARe 8,3%), cinco controles positivos-disbiosis y 15 controles-eubiosis. El tratamiento convencional en 42,9%, anti-IL-17 16,3%, y anti-TNF 40,8%. Por subtipo-EasP, se encontraron diferencias estadísticamente significativas a favor de EA para los índices de diversidad. Entre EA vs APs, hubo diferencia a favor de EA para Clostridium clostridioforme (p=0,002), Gemmiger formicilis (p=0,009), Roseburia inulivorans (p=0,008) y Lachnospira pectinoschiza. Entre EA vs ARe hubo diferencia a favor de EA para L. pectinoschiza (p=0,009), Ruminococcus callidus (p = 0,006), Clostridium ruminantium (p=0,031); G. formicilis (p=0,034). La diversidad y riqueza mostraron diferencias en pacientes con alta actividad para los índices de Simpson y Pielou. En alta actividad, se encontró menor enriquecimiento de Bacteroides eggerthii (p=0,0003), C. ruminantium (p= 0,026) y Alistipes putredinis (p= 0,035). El número de ASV fue superior en el grupo de anti IL-17 vs convencional (p=0.025), y una tendencia entre anti IL-17 vs anti-TNF (p=0,09). En anti TNF hubo menor proporción para C. clostridioforme (p=0,023), G. formicilis (p=0,030) y R. callidus (p= 0,003). Y en anti IL-17, Alistipes indistinctus (p= 0,012), estuvo disminuida. CONCLUSIONES: Existen diferencias en la diversidad microbiana para los subtipos de EspA. El nivel de actividad de la enfermedad es plausible para influir en la composición de microbiota fecal. El tratamiento con anti-TNFα, puede influenciar el ambiente del microbioma favoreciendo la restauración de la microbiota intestinal, mientras los anti IL-17 podrían mantener un ambiente inflamatorio.

Role of the Gut Microbiota in Osteoarthritis, Rheumatoid Arthritis, and Spondylarthritis: An Update on the Gut-Joint Axis.

Dysregulation of the gut microbiota and their metabolites is involved in the pathogenic process of intestinal diseases, and several pieces of evidence within the current literature have also highlighted a possible connection between the gut microbiota and the unfolding of inflammatory pathologies of the joints. This dysregulation is defined as the "gut-joint axis" and is based on the joint-gut interaction. It is widely recognized that the microbiota of the gut produce a variety of compounds, including enzymes, short-chain fatty acids, and metabolites. As a consequence, these proinflammatory compounds that bacteria produce, such as that of lipopolysaccharide, move from the "leaky gut" to the bloodstream, thereby leading to systemic inflammation which then reaches the joints, with consequences such as osteoarthritis, rheumatoid arthritis, and spondylarthritis. In this state-of-the-art research, the authors describe the connections between gut dysbiosis and osteoarthritis, rheumatoid arthritis, and spondylarthritis. Moreover, the diagnostic tools, outcome measures, and treatment options are elucidated. There is accumulating proof suggesting that the microbiota of the gut play an important part not only in immune-mediated, metabolic, and neurological illnesses but also in inflammatory joints. According to the authors, future studies should concentrate on developing innovative microbiota-targeted treatments and their effects on joint pathology as well as on organizing screening protocols to predict the onset of inflammatory joint disease based on gut dysbiosis.

Efficacy and safety of gut microbiota-based therapies in autoimmune and rheumatic diseases: a systematic review and meta-analysis of 80 randomized controlled trials.

BACKGROUND: Previous randomized controlled trials (RCTs) suggested that gut microbiota-based therapies may be effective in treating autoimmune diseases, but a systematic summary is lacking. METHODS: Pubmed, EMbase, Sinomed, and other databases were searched for RCTs related to the treatment of autoimmune diseases with probiotics from inception to June 2022. RevMan 5.4 software was used for meta-analysis after 2 investigators independently screened literature, extracted data, and assessed the risk of bias of included studies. RESULTS: A total of 80 RCTs and 14 types of autoimmune disease [celiac sprue, SLE, and lupus nephritis (LN), RA, juvenile idiopathic arthritis (JIA), spondyloarthritis, psoriasis, fibromyalgia syndrome, MS, systemic sclerosis, type 1 diabetes mellitus (T1DM), oral lichen planus (OLP), Crohn's disease, ulcerative colitis] were included. The results showed that gut microbiota-based therapies may improve the symptoms and/or inflammatory factor of celiac sprue, SLE and LN, JIA, psoriasis, PSS, MS, systemic sclerosis, Crohn's disease, and ulcerative colitis. However, gut microbiota-based therapies may not improve the symptoms and/or inflammatory factor of spondyloarthritis and RA. Gut microbiota-based therapies may relieve the pain of fibromyalgia syndrome, but the effect on fibromyalgia impact questionnaire score is not significant. Gut microbiota-based therapies may improve HbA1c in T1DM, but its effect on total insulin requirement does not seem to be significant. These RCTs showed that probiotics did not increase the incidence of adverse events. CONCLUSIONS: Gut microbiota-based therapies may improve several autoimmune diseases (celiac sprue, SLE and LN, JIA, psoriasis, fibromyalgia syndrome, PSS, MS, T1DM, Crohn's disease, and ulcerative colitis).

Investigation of the acute pathogenesis of spondyloarthritis/HLA-B27-associated anterior uveitis based on genome-wide association analysis and single-cell transcriptomics.

BACKGROUND: Patients with spondyloarthritis (SpA)/HLA-B27-associated acute anterior uveitis (AAU) experience recurring acute flares, which pose significant visual and financial challenges. Despite established links between SpA and HLA-B27-associated AAU, the exact mechanism involved remains unclear, and further understanding is needed for effective prevention and treatment. METHODS: To investigate the acute pathogenesis of SpA/HLA-B27-associated AAU, Mendelian randomization (MR) and single-cell transcriptomic analyses were employed. The MR incorporated publicly available protein quantitative trait locus data from previous studies, along with genome-wide association study data from public databases. Causal relationships between plasma proteins and anterior uveitis were assessed using two-sample MR. Additionally, colocalization analysis was performed using Bayesian colocalization. Single-cell transcriptome analysis utilized the anterior uveitis dataset from the Gene Expression Omnibus (GEO) database. Dimensionality reduction, clustering, transcription factor analysis, pseudotime analysis, and cell communication analysis were subsequently conducted to explore the underlying mechanisms involved. RESULTS: Mendelian randomization analysis revealed that circulating levels of AIF1 and VARS were significantly associated with a reduced risk of developing SpA/HLA-B27-associated AAU, with AIF1 showing a robust correlation with anterior uveitis onset. Colocalization analysis supported these findings. Single-cell transcriptome analysis showed predominant AIF1 expression in myeloid cells, which was notably lower in the HLA-B27-positive group. Pseudotime analysis revealed dendritic cell terminal positions in differentiation branches, accompanied by gradual decreases in AIF1 expression. Based on cell communication analysis, CD141+CLEC9A+ classic dendritic cells (cDCs) and the APP pathway play crucial roles in cellular communication in the Spa/HLA-B27 group. CONCLUSIONS: AIF1 is essential for the pathogenesis of SpA/HLA-B27-associated AAU. Myeloid cell differentiation into DCs and decreased AIF1 levels are also pivotal in this process.

Factors associated with acute anterior uveitis history in patients with axial spondyloarthritis: Results of a longitudinal study.

BACKGROUNDS: Acute anterior uveitis (AAU) is the most common extra-musculoskeletal manifestation in axial spondyloarthritis (axSpA). OBJECTIVES: The aim of the study is to evaluate the factors associated with AAU attacks in patients with axSpA during a 36-month follow-up period. METHODS: In total, 469 patients with axSpA were included in this observational study. Demographic data, clinical characteristics, disease activity measurements, and treatment patterns were compared between patients with and without a history of AAU. The development of AAU and its related factors were investigated using generalized estimating equations, which is a technique for longitudinal data analysis. RESULTS: Overall, 99 (21%) out of 469 patients experienced at least one AAU attack, with 77 patients (78%) having a history of AAU and 53 patients (58% of whom had a history of AAU) experiencing AAU attacks during the follow-up period. At baseline, patients with a history of AAU were found to be older (p = .001), be more likely to have peripheral arthritis (p < .001), have higher serum CRP levels (p = .016), have a higher frequency of sulfasalazine (SLZ) and tumor necrosis factor inhibitors (TNFi) use (p < .001 and p < .001, respectively). In the longitudinal analysis, having a history of AAU was identified as the only independent determinant of the development of AAU. CONCLUSIONS: AAU history might be a risk factor for the development of AAU attacks in patients with axSpA. Although TNFi and SLZ were prescribed more frequently to patients with a history of AAU, the effectiveness of these agents in preventing further AAU attacks was not demonstrated.