Identifying circRNA-associated-ceRNA networks in juvenile spondyloarthropathies patients.

BACKGROUND: Juvenile spondyloarthropathies (JSpA) are defined as a heterogeneous group of diseases that start before the age of 16. The study aimed to identify key genes and pathways that are influenced by circRNAs and to screen potential therapeutic agents for JSpA. The study involved the analysis of circRNA expression profiles, identification of circRNA-miRNA-mRNA regulatory networks, and functional annotation of differentially expressed genes. The results of the study may have provided insights into the molecular mechanisms underlying JSpA and potential therapeutic targets for this disease. METHODS: In this study, sequencing data of circRNA, miRNA, and mRNA were obtained from the GEO datasets. The data were then analyzed to identify candidates for constructing a circRNA-miRNA-mRNA network based on circRNA-miRNA interactions and miRNA-mRNA interactions. Functional enrichments of genes were performed using the DAVID database. A PPI network was constructed using the STRING database and visualized using Cytoscape software. The MCODE plugin app was used to explore hub genes in the PPI network. The expression changes in immune cells were assessed using the online CIBERSORT algorithm to obtain the proportion of various types of immune cells. Finally, the Connectivity Map L1000 platform was used to identify potential agents for JSpA treatment. Overall, this study aimed to provide a comprehensive understanding of the molecular mechanisms underlying JSpA and to identify potential therapeutic agents for this disease. RESULTS: A total of 225 differentially expressed circRNAs (DEcircRNAs), 23 differentially expressed miRNAs (DEmiRNAs) and 1324 differentially expressed mRNAs (DEmRNAs) were identified. We integrated 5 overlapped circRNAs, 7 miRNAs and 299 target mRNAs into a circRNA-miRNA-mRNA network. We next identified 10 hub genes based on the PPI network. KEGG pathway analysis revealed that the DEGs were mainly associated with JAK-STAT signal pathway. We found that neutrophils accounted for the majority of all enriched cells. In addition, we discovered several chemicals as potential treatment options for JSpA. CONCLUSIONS: Through this bioinformatics analysis, we suggest a regulatory role for circRNAs in the pathogenesis and treatment of JSpA from the view of a competitive endogenous RNA (ceRNA) network.

Evaluation of co-existing diseases in children with familial Mediterranean fever.

Familial Mediterranean fever (FMF) is A common periodic fever syndrome. The causative gene of the FMF is named Mediterranean Fever gene (MEFV). Increased inflammation in FMF may play a role as a trigger for the development of some diseases. The objective of the study is to evaluate the frequency of comorbid disorders in children followed up with diagnosis of FMF. Additionally, we aimed to assess the association between FMF and other inflammatory conditions in a large pediatric FMF cohort. A total of 686 FMF patients were included in the cross-sectional study. A questionnaire including questions about characteristics of fever episodes, presence of arthralgia, arthritis, abdominal pain, chest pain during and co-existence of any other disease diagnosed by a physician was filled out by face-to-face interviews with patients or their parents. Female-male ratio was 0.85. Median age at the time of study, age at disease onset and at the time of diagnosis were 12.9 (1.7-22.3), 3 (0.08-17), and 6 (0.75-17) years, respectively. In 130 (18.9%) FMF patients we detected co-existing inflammatory condition. The most common co-existing diseases were: juvenile idiopathic arthritis 42 (6.1%), asthma/reactive airway disease 29 (4.2%), Henoch-Schönlein purpura 20 (2.9%), uveitis 12 (1.7%) and inflammatory bowel disease 10 (1.4%). Except for asthma/reactive airway disease and inflammatory bowel disease, there was no significant difference regarding the type of MEFV gene mutation. We have reported increased frequencies of various inflammatory conditions and decreased frequency of asthma in patients with FMF.

Imaging of juvenile spondyloarthritis. Part II: Ultrasonography and magnetic resonance imaging.

Juvenile spondyloarthropathies are mainly manifested by symptoms of peripheral arthritis and enthesitis. Early involvement of sacroiliac joints and spine is exceptionally rare in children; this usually happens in adulthood. Conventional radiographs visualize late inflammatory lesions. Early diagnosis is possible with the use of ultrasonography and magnetic resonance imaging. The first part of the article presented classifications and radiographic presentation of juvenile spondyloarthropathies. This part discusses changes seen on ultrasonography and magnetic resonance imaging. In patients with juvenile spondyloarthropathies, these examinations are conducted to diagnose inflammatory lesions in peripheral joints, tendon sheaths, tendons and bursae. Moreover, magnetic resonance also shows subchondral bone marrow edema, which is considered an early sign of inflammation. Ultrasonography and magnetic resonance imaging do not show specific lesions for any rheumatic disease. Nevertheless, they are conducted for early diagnosis, treatment monitoring and identifying complications. This article presents a spectrum of inflammatory changes and discusses the diagnostic value of ultrasonography and magnetic resonance imaging.

The performance of classification criteria for juvenile spondyloarthropathies.

Juvenile spondyloarthropathies (JSpA) are a group of rheumatologic diseases with a disease onset before 16; characterized with enthesitis, lower extremity oligoarthritis, involvement of the axial skeleton and HLA B27 positivity. The diversity of classification criteria along with the phenotype heterogeneity makes the classification of JSpA challenging. The aim of our study was to evaluate the performance of the pre-determined and recently proposed classification criteria for JSpA. The study group consisted of 113 patients with JSpA and 150 patients with juvenile idiopathic arthritis (JIA). Eligible criteria for JSpA were applied to all of the enrolled patients. The analysis of sensitivity, specificity and the kappa index were used to verify the performance of the JSpA criteria. The Amor criteria showed the highest sensitivity (98.2%) while the ASAS criteria for the axial SpA had highest specificity (100%). The sensitivity and specificity of the remaining criteria were: 93.8 and 63.8% for ESSG, 95.6 and 62.7% for Garmisch-Partenkirchen, 91.2 and 75.3% for ASAS criteria for peripheral SpA, respectively. Criteria proposed by our group showed the high sensitivity, specificity and kappa value: 90.3, 90.7, 0.843%, respectively. We suggest that criteria proposed by us could be used in the classification of JSpA. However, neither the pre-determined nor the new criteria are totally adequate and efficacious for the classification and diagnosis of this disease. The evaluation of the validity and reliability of proposed criteria in multicentric studies are mandatory, to increase its utility in routine clinical practice.

Imaging of Juvenile Idiopathic Arthritis.

Juvenile idiopathic arthritis is an umbrella term covering several distinct categories that share common features. The European League Against Rheumatism and the Pediatric Rheumatology European Society have published a consensus article with recommendations to guide radiologists and clinicians in choosing the best imaging technique for each particular clinical setting. A reproducible, accurate, validated, and long-established scoring system to use in everyday practice for monitoring and predicting long-term response to therapy is still to be developed on MR imaging for each joint.

Imaging of juvenile idiopathic arthritis. Part I: Clinical classifications and radiographs.

Juvenile idiopathic arthritis is the most common autoimmune systemic disease of the connective tissue affecting individuals at the developmental age. Radiography is the primary modality employed in the diagnostic imaging in order to identify changes typical of this disease entity and rule out other bone-related pathologies, such as neoplasms, posttraumatic changes, developmental defects and other forms of arthritis. The standard procedure involves the performance of comparative joint radiographs in two planes. Radiographic changes in juvenile idiopathic arthritis are detected in later stages of the disease. Bone structures are assessed in the first place. Radiographs can also indirectly indicate the presence of soft tissue inflammation (i.e. in joint cavities, sheaths and bursae) based on swelling and increased density of the soft tissue as well as dislocation of fat folds. Signs of articular cartilage defects are also seen in radiographs indirectly - based on joint space width changes. The first part of the publication presents the classification of juvenile idiopathic arthritis and discusses its radiographic images. The authors list the affected joints as well as explain the spectrum and specificity of radiographic signs resulting from inflammatory changes overlapping with those caused by the maturation of the skeletal system. Moreover, certain dilemmas associated with the monitoring of the disease are reviewed. The second part of the publication will explain issues associated with ultrasonography and magnetic resonance imaging, which are more and more commonly applied in juvenile idiopathic arthritis for early detection of pathological features as well as the disease complications.

Imaging of juvenile idiopathic arthritis. Part II: Ultrasonography and MRI.

Juvenile idiopathic arthritis is the most common autoimmune systemic disease of the connective tissue affecting individuals in the developmental age. Radiography, which was described in the first part of this publication, is the standard modality in the assessment of this condition. Ultrasound and magnetic resonance imaging enable early detection of the disease which affects soft tissues, as well as bones. Ultrasound assessment involves: joint cavities, tendon sheaths and bursae for the presence of synovitis, intraand extraarticular fat tissue to visualize signs of inflammation, hyaline cartilage, cartilaginous epiphysis and subchondral bone to detect cysts and erosions, and ligaments, tendons and their entheses for signs of enthesopathies and tendinopathies. Magnetic resonance imaging is indicated in children with juvenile idiopathic arthritis for assessment of inflammation in peripheral joints, tendon sheaths and bursae, bone marrow involvement and identification of inflammatory lesions in whole-body MRI, particularly when the clinical picture is unclear. Also, MRI of the spine and spinal cord is used in order to diagnose synovial joint inflammation, bone marrow edema and spondylodiscitis as well as to assess their activity, location, and complications (spinal canal stenosis, subluxation, e.g. in the atlantoaxial region). This article discusses typical pathological changes seen on ultrasound and magnetic resonance imaging. The role of these two methods for disease monitoring, its identification in the pre-clinical stage and establishing its remission are also highlighted.

HLA B27 typing in 511 children with juvenile idiopathic arthritis from India.

The enthesitis-related arthritis (ERA) category of juvenile idiopathic arthritis (JIA) is the most common category in India. HLA B27 has a high prevalence in ERA, and ILAR classification includes it in exclusion criteria for other categories, but due to its cost, it is not routinely done. We undertook this study to assess the prevalence of HLA B27 in ERA and other groups of juvenile arthritis in India. Consecutive patients of JIA ERA and select patients from other categories were recruited from a single tertiary care hospital over a span of 3 years. HLA B27 was tested using PCR. Five hundred and eleven children were studied: 312 had ERA, and 199 had other categories (29 oligoarthritis, 107 polyarthritis, 44 systemic onset JIA, 9 psoriatic arthritis and 10 undifferentiated). The prevalence of HLA B27 was highest in the ERA group (87 %) and correlated with the presence of sacroiliitis. Prevalence was 10.3 % in oligoarthritis, 16 % in polyarticular rheumatoid factor (RF)-positive arthritis, 26 % in RF-negative polyarticular arthritis, 66 % in psoriatic arthritis and 40 % in the unclassified and 0 % in systemic onset category. Twenty-seven children had a change in category of JIA as per ILAR owing to HLA B27 testing positive, most commonly in the RF-negative polyarthritis group. Only six of these had clinical features suggestive of Spondyloarthropathy. There is high prevalence of HLA B27 in ERA. Though HLA B27 testing helps in correct classification, a minority of these patients have features suggestive of spondyloarthropathy like back pain, enthesitis or sacroiliitis.

Juvenile Spondyloarthropathies.

Juvenile spondyloarthropathies represent a clinical entity separate from the adult disease. Initial clinical signs of juvenile spondyloarthropathies often include lower extremity arthritis and enthesopathy, without axial involvement at the disease onset. Asymmetrical oligoarthritis of lower extremities is typically seen in this type of arthritis. Enthesopathy, which is the hallmark of the disease, is most commonly seen in the Achilles tendon, being manifested by heel pain. Anterior uveitis and HLA-B27 positivity are seen in a proportion of cases. Sacroiliitis is generally asymptomatic in the pediatric population. Ineffective treatment of childhood disease results in disease progression to typical adult form of ankylosing spondylitis. Therefore, early diagnosis and classification remains one of the most relevant questions in pediatric rheumatology. It should be kept in mind that the disease could be misdiagnosed as FMF or Behçet's syndrome in countries with a high incidence of those conditions. This review revises available classification criteria, clinical manifestations and therapeutic options for patients with juvenile spondyloarthropathies.

Espondiloartropatía juvenil: una visión desde la pediatría / Juvenile spondyloarthropathy: a view from pediatrics

La espondiloartropatía juvenil (EAPj) representa un grupo de artropatías crónicas que se inician en la infancia y que corresponden a entidades cuyas clasificaciones se han modificado en el transcurso de las décadas. Las clasificaciones actuales las incluyen sólo parcialmente. Las manifestaciones clínicas incluyen compromiso articular periférico asimétrico, entesis, sacroilíaco y menos frecuentemente de columna han permitido agruparlas en cinco categorías entre el que se encuentra la forma anquilosante juvenil relacionada con HLA B27 (+), el prototipo de EAPj y que podría representar a la forma de inicio de espondiloartropatía anquilosante del adulto. Los recientes avances en los estudios genéticos, en la patogenia, el desarrollo de mejores técnicas de imagenología tales como la ecografía musculo-esquelética y resonancia magnética aplicada a la Reumatología pediátrica podrían contribuir a generar criterios de clasificación de manera tal que faciliten la comunicación científica con los Reumatólogos de adultos. Un diagnóstico precoz, la aplicación de medidas de actividad de la enfermedad validadas y el oportuno manejo terapéutico obtendrán un pronóstico más favorable. Los resultados terapéuticos en EAPj presentan evidencia limitada aún requiriéndose mayor tiempo de evolución para obtener resultados a largo plazo.

Juvenile spondyloarthropathy (EAPj) represents a heterogeneous group of juvenile articular inflammatory entities and their classification have been changed during the last decades. The current classifications include only partially. The clinical manifestations of diseases involves peripheral joints, enthesis, sacroiliac and less frequently spine and they are classified in five specific subgroups among which is the juvenile ankylosing HLA B27 (+); the EAPj’s prototype and that may represent one of ankylosing spondyloarthropathy adult diseases. Recently, novel insights into the epidemiology, pathogenesis, and development of the imaging techniques such as muscle-skeletal ultrasound and magnetic resonance applied to pediatric rheumatology could be contributing to new classification criteria in order to facilitate the scientific communication with Rheumatologist of adult patients. An early diagnosis a validated measures of disease activity and treatment can change the course and outcome of disease.

Radiological imaging in pediatric rheumatic diseases.

Radiological imaging plays a fundamental role in the diagnosis and monitoring of rheumatic diseases. The basic method of imaging is a classic X-ray picture, which for many years has been used as a single method for the recognition and evaluation of the effects of disease management. In today's modern day treatment of rheumatic diseases, ultrasonography and magnetic resonance are more commonly performed for early detection of inflammatory changes in the region of soft tissue, subchondral bone and bone marrow. In spite of their usefulness and fundamental role in the diagnosis, X-ray still remains an essential tool in the diagnosis of rheumatoid arthritis in children and is complementary to today's methods of imaging diagnostics. In clinical practice, X-ray imaging is still an important examination performed not only to recognize the disorders, but also to provide a differential diagnosis. It helps estimate disease progression and is used to monitor the effects of treatment and the development of possible complications. Differential diagnosis of rheumatic diseases is performed on the basis of localization and type of radiographic changes. The surrounding periarticular soft tissues, bone structures, joint space, with special attention to articular bone surfaces and epiphyses, are analyzed. The aim of this work is to describe characteristic inflammatory changes present on X-ray imaging typical for the most commonly diagnosed rheumatic diseases in children, such as juvenile idiopathic arthritis, systemic lupus erythematosus, systemic scleroderma, mixed connective tissue disease, juvenile dermatomyositis, juvenile spondyloarthropathy and systemic vascular disease.