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Trends in Molecular Medicine Oct 2017Arthritis represents a family of complex joint pathologies responsible for the majority of musculoskeletal conditions. Nearly all diseases within this family, including... (Review)
Review
Arthritis represents a family of complex joint pathologies responsible for the majority of musculoskeletal conditions. Nearly all diseases within this family, including osteoarthritis, rheumatoid arthritis, and juvenile idiopathic arthritis, are chronic conditions with few or no disease-modifying therapeutics available. Advances in genome engineering technology, most recently with CRISPR-Cas9, have revolutionized our ability to interrogate and validate genetic and epigenetic elements associated with chronic diseases such as arthritis. These technologies, together with cell reprogramming methods, including the use of induced pluripotent stem cells, provide a platform for human disease modeling. We summarize new evidence from genome-wide association studies and genomics that substantiates a genetic basis for arthritis pathogenesis. We also review the potential contributions of genome engineering in the development of new arthritis therapeutics.
Topics: Animals; Arthritis; CRISPR-Cas Systems; Gene Editing; Genome, Human; Genome-Wide Association Study; Humans; Precision Medicine
PubMed: 28887050
DOI: 10.1016/j.molmed.2017.08.002 -
Current Allergy and Asthma Reports Feb 2021The purpose of this review is to provide a framework to distinguish Blau syndrome/Early Onset Sarcoidosis and Sarcoidosis clinically. We also discuss relevant... (Review)
Review
PURPOSE OF REVIEW
The purpose of this review is to provide a framework to distinguish Blau syndrome/Early Onset Sarcoidosis and Sarcoidosis clinically. We also discuss relevant differences in genetics, pathogenesis, and management of these diseases.
RECENT FINDINGS
Blau syndrome and Sarcoidosis share the characteristic histologic finding of noncaseating granulomas as well as some similar clinical characteristics; nevertheless, they are distinct entities with important differences between them. Blau syndrome and Early Onset Sarcoidosis are due to one of numerous possible gain-of-function mutations in NOD2, commonly presenting before age 5 with a triad of skin rash, arthritis, and uveitis. However, as more cases are reported, expanded clinical manifestations have been described. In systemic Sarcoidosis, there are numerous susceptibility genes that have been identified, and disease is thought to result from an environmental exposure in a genetically susceptible host. It most often presents with constitutional symptoms and pulmonary involvement and typically affects adolescents and adults. This paper reviews the similarities and differences between Blau syndrome and Sarcoidosis. We also discuss the importance of distinguishing between them, particularly with regard to prognosis and outcomes.
Topics: Arthritis; Diagnosis, Differential; Granuloma; Humans; Mutation; Nod2 Signaling Adaptor Protein; Prognosis; Sarcoidosis; Synovitis; Uveitis
PubMed: 33560445
DOI: 10.1007/s11882-021-00991-3 -
Biomedical Journal Feb 2024Nod-like receptors (NLRs) are innate immune receptors that play a key role in sensing components from pathogens and from damaged cells or organelles. NLRs form signaling... (Review)
Review
Nod-like receptors (NLRs) are innate immune receptors that play a key role in sensing components from pathogens and from damaged cells or organelles. NLRs form signaling complexes that can lead to activation of transcription factors or effector caspases - by means of inflammasome activation -Inflammatory arthritis (IA) culminating in promoting inflammation. An increasing body of research supports the role of NLRs in driving pathogenesis of IA, a collection of diseases that include rheumatoid arthritis (RA), psoriatic arthritis (PsA), ankylosing spondylitis, and pediatric arthritis. In this review, we briefly discuss the main drivers of IA diseases and dive into the evidence for - and against - various NLRs in driving these diseases. We also review the studies examining the use of NLR and inflammasome inhibitors as potential therapies for IA.
Topics: Humans; Child; Arthritis, Psoriatic; Inflammasomes; NLR Proteins; Arthritis, Rheumatoid; Spondylitis, Ankylosing
PubMed: 37598797
DOI: 10.1016/j.bj.2023.100655 -
Clinical Rheumatology Jun 2022Most accepted definitions of reactive arthritis (ReA) consider it a type of spondyloarthritis (SpA) precipitated by a gut or urogenital infection. A wider definition... (Review)
Review
Most accepted definitions of reactive arthritis (ReA) consider it a type of spondyloarthritis (SpA) precipitated by a gut or urogenital infection. A wider definition considers any arthritis that occurs after a mucosal surface infection as ReA. There is limited consensus regarding a working definition, status of HLA-B27, or even classification criteria for ReA. This may also contribute to a lack of systemic studies or clinical trials for ReA, thereby reducing further treatment recommendations to expert opinions only. The emergence of post-COVID-19 ReA has brought the focus back on this enigmatic entity. Post-COVID-19 ReA can present at extremes of age, appears to affect both sexes equally and can have different presentations. Some present with small joint arthritis, others with SpA phenotype-either with peripheral or axial involvement, while a few have only tenosynovitis or dactylitis. The emergence of post-vaccination inflammatory arthritis hints at similar pathophysiology involved. There needs to be a global consensus on whether or not to include all such conditions under the umbrella of ReA. Doing so will enable studies on uniform groups on how infections precipitate arthritis and what predicts chronicity. These have implications beyond ReA and might be extrapolated to other inflammatory arthritides. Key Points • Classical reactive arthritis (ReA) has a spondyloarthritis phenotype and is preceded by symptomatic gut or urogenital infection • The demonstration of antigen and nucleic acid sequences of pathogens in synovium has blurred the difference between invasive arthritis and reactive arthritis • Post-COVID-19 ReA has a transient phenotype and can have different presentations. All reported cases are self-limiting • The large amount of literature reporting post-COVID-19 ReA calls for introspection if the existing definitions of ReA need to be updated.
Topics: Arthritis, Reactive; COVID-19; Female; HLA-B27 Antigen; Humans; Male; Pandemics; Spondylarthritis
PubMed: 35247132
DOI: 10.1007/s10067-022-06120-3 -
International Journal of Molecular... Jun 2023Arthritis has a high prevalence globally and includes over 100 types, the most common of which are rheumatoid arthritis (RA), osteoarthritis (OA), psoriatic arthritis...
Arthritis has a high prevalence globally and includes over 100 types, the most common of which are rheumatoid arthritis (RA), osteoarthritis (OA), psoriatic arthritis (PsA), and inflammatory arthritis [...].
Topics: Humans; Arthritis, Psoriatic; Synovial Fluid; Arthritis, Rheumatoid; Osteoarthritis
PubMed: 37373313
DOI: 10.3390/ijms241210166 -
Rheumatic Diseases Clinics of North... Nov 2021Spondyloarthritis represents a group of disorders characterized by enthesitis and axial skeletal involvement. Juvenile spondyloarthritis begins before age 16. Joint... (Review)
Review
Spondyloarthritis represents a group of disorders characterized by enthesitis and axial skeletal involvement. Juvenile spondyloarthritis begins before age 16. Joint involvement is usually asymmetric. Bone marrow edema on noncontrast MRI of the sacroiliac joints can facilitate diagnosis. The most significant risk factor for axial disease is HLA-B27. Most patients have active disease into adulthood. Enthesitis and sacroiliitis correlate with greater pain intensity and poor quality-of-life measures. Tumor necrosis factor inhibitors are the mainstay of biologic therapy. Although other biologics such as IL-17 blockers have shown benefit in adult spondyloarthritis, none are approved by the US Food and Drug Administration.
Topics: Adolescent; Adult; Arthritis, Juvenile; Humans; Magnetic Resonance Imaging; Sacroiliac Joint; Sacroiliitis; Spondylarthritis; Spondylitis, Ankylosing
PubMed: 34635292
DOI: 10.1016/j.rdc.2021.07.001 -
Frontiers in Immunology 2023The Ras (rat sarcoma virus) is a GTP-binding protein that is considered one of the important members of the Ras-GTPase superfamily. The Ras involves several pathways in... (Review)
Review
The Ras (rat sarcoma virus) is a GTP-binding protein that is considered one of the important members of the Ras-GTPase superfamily. The Ras involves several pathways in the cell that include proliferation, migration, survival, differentiation, and fibrosis. Abnormalities in the expression level and activation of the Ras family signaling pathway and its downstream kinases such as Raf/MEK/ERK1-2 contribute to the pathogenic mechanisms of rheumatic diseases including immune system dysregulation, inflammation, and fibrosis in systemic sclerosis (SSc); destruction and inflammation of synovial tissue in rheumatoid arthritis (RA); and autoantibody production and immune complexes formation in systemic lupus erythematosus (SLE); and enhance osteoblast differentiation and ossification during skeletal formation in ankylosing spondylitis (AS). In this review, the basic biology, signaling of Ras, and abnormalities in this pathway in rheumatic diseases including SSc, RA, AS, and SLE will be discussed.
Topics: Humans; Arthritis, Rheumatoid; Spondylitis, Ankylosing; Rheumatic Diseases; Inflammation; Lupus Erythematosus, Systemic; Rheumatic Fever; Scleroderma, Systemic; Signal Transduction; Fibrosis
PubMed: 37256120
DOI: 10.3389/fimmu.2023.1151246 -
Arthritis & Rheumatology (Hoboken, N.J.) Jan 2018Current classification of primary inflammatory arthritis begins from the assumption that adults and children are different. No form of juvenile idiopathic arthritis... (Review)
Review
Current classification of primary inflammatory arthritis begins from the assumption that adults and children are different. No form of juvenile idiopathic arthritis bears the same name as an adult arthritis, a nomenclature gap with implications for both clinical care and research. Recent genetic data have raised questions regarding this adult/pediatric divide, revealing instead broad patterns that span the age spectrum. Combining these genetic patterns with demographic and clinical data, we propose that inflammatory arthritis can be segregated into 4 main clusters, largely irrespective of pediatric or adult onset: seropositive, seronegative (likely including a distinct group that usually begins in early childhood), spondyloarthritis, and systemic. Each of these broad clusters is internally heterogeneous, highlighting the need for further study to resolve etiologically discrete entities. Eliminating divisions based on arbitrary age cutoffs will enhance opportunities for collaboration between adult and pediatric rheumatologists, thereby helping to promote the understanding and treatment of arthritis.
Topics: Adult; Arthritis; Child; Child, Preschool; Diagnosis, Differential; Female; Genetic Predisposition to Disease; Humans; Male
PubMed: 29024575
DOI: 10.1002/art.40350 -
JCI Insight Mar 2019Inflammatory arthritis encompasses a set of common diseases characterized by immune-mediated attack on joint tissues. Most but not all affected patients manifest... (Review)
Review
Inflammatory arthritis encompasses a set of common diseases characterized by immune-mediated attack on joint tissues. Most but not all affected patients manifest circulating autoantibodies. Decades of study in human and animal arthritis have identified key roles for autoantibodies in immune complexes and through direct modulation of articular biology. However, joint inflammation can arise because of pathogenic T cells and other pathways that are antibody-independent. Here we review the evidence for these parallel tracks, in animal models and in humans, to explore the range of mechanisms engaged in the pathophysiology of arthritis and to highlight opportunities for targeted therapeutic intervention.
Topics: Animals; Antigen-Antibody Complex; Arthritis; Arthritis, Rheumatoid; Autoantibodies; Disease Models, Animal; Glycosylation; Humans; Immunoglobulin G; T-Lymphocytes
PubMed: 30843881
DOI: 10.1172/jci.insight.125278 -
International Journal of Molecular... Jun 2023Collagens serve essential mechanical functions throughout the body, particularly in the connective tissues. In articular cartilage, collagens provide most of the... (Review)
Review
Collagens serve essential mechanical functions throughout the body, particularly in the connective tissues. In articular cartilage, collagens provide most of the biomechanical properties of the extracellular matrix essential for its function. Collagen plays a very important role in maintaining the mechanical properties of articular cartilage and the stability of the ECM. Noteworthily, many pathogenic factors in the course of osteoarthritis and rheumatoid arthritis, such as mechanical injury, inflammation, and senescence, are involved in the irreversible degradation of collagen, leading to the progressive destruction of cartilage. The degradation of collagen can generate new biochemical markers with the ability to monitor disease progression and facilitate drug development. In addition, collagen can also be used as a biomaterial with excellent properties such as low immunogenicity, biodegradability, biocompatibility, and hydrophilicity. This review not only provides a systematic description of collagen and analyzes the structural characteristics of articular cartilage and the mechanisms of cartilage damage in disease states but also provides a detailed characterization of the biomarkers of collagen production and the role of collagen in cartilage repair, providing ideas and techniques for clinical diagnosis and treatment.
Topics: Humans; Osteoarthritis; Arthritis, Rheumatoid; Collagen; Extracellular Matrix; Cartilage, Articular
PubMed: 37372989
DOI: 10.3390/ijms24129841