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Clinical Medicine (London, England) Feb 2017Psoriatic arthritis (PsA) accounts for around 20% of referrals to the early arthritis clinic and presents a significant diagnostic and management challenge. Early... (Review)
Review
Psoriatic arthritis (PsA) accounts for around 20% of referrals to the early arthritis clinic and presents a significant diagnostic and management challenge. Early diagnosis is important to prevent long term functional disability and to ensure optimal management of arthritis and key comorbidities. From the rheumatologist's perspective, the differential diagnosis includes rheumatoid arthritis, gout and other inflammatory arthritides. Once diagnosed, it is essential to assess the disease fully, including arthritis, enthesitis, dactylitis, skin/nail disease and axial involvement. Using this information, appropriate treatment can be planned using therapies that are effective at treating the relevant domains of disease. Despite poor data, traditional disease-modifying anti-rheumatic drugs are commonly used and have been effective in observational studies. Following tumour necrosis factor inhibitors, which have proven excellent efficacy in multiple domains of PsA, new biologics are available or in development and will improve treatment options for people with refractory PsA.
Topics: Arthritis, Psoriatic; Humans
PubMed: 28148584
DOI: 10.7861/clinmedicine.17-1-65 -
Best Practice & Research. Clinical... Aug 2020Antisynthetase syndrome (ASyS) is an autoimmune disease clinically manifested most often by interstitial lung disease, myositis, and arthritis. Raynaud's syndrome,... (Review)
Review
Antisynthetase syndrome (ASyS) is an autoimmune disease clinically manifested most often by interstitial lung disease, myositis, and arthritis. Raynaud's syndrome, fever, and rashes are also commonly seen. This syndrome is characterized by the highly specific presence of antibodies against various aminoacyl transfer RNA synthetases, including Jo-1 and others. In this chapter, we provide an overview of ASyS, including pathogenesis, common clinical manifestations, and treatment strategies. We discuss the spectrum of disease seen with specific antisynthetase antibodies and examine the differences in phenotype between patients with different antisynthetase antibodies. We outline common treatment strategies, which should generally target the most severe and life- or organ-threatening disease manifestations. Finally, we discuss short- and long-term prognosis in ASyS.
Topics: Amino Acyl-tRNA Synthetases; Antibodies, Antinuclear; Arthritis; Autoantibodies; Humans; Lung Diseases, Interstitial; Myositis
PubMed: 32284267
DOI: 10.1016/j.berh.2020.101503 -
Veterinary Pathology Sep 2015Rheumatoid arthritis (RA) is a chronic debilitating autoimmune disorder characterized by synovitis that leads to cartilage and bone erosion by invading fibrovascular... (Review)
Review
Rheumatoid arthritis (RA) is a chronic debilitating autoimmune disorder characterized by synovitis that leads to cartilage and bone erosion by invading fibrovascular tissue. Mouse models of RA recapitulate many features of the human disease. Despite the availability of medicines that are highly effective in many patient populations, autoimmune diseases (including RA) remain an area of active biomedical research, and consequently mouse models of RA are still extensively used for mechanistic studies and validation of therapeutic targets. This review aims to integrate morphologic features with model biology and cover the key characteristics of the most commonly used induced and spontaneous mouse models of RA. Induced models emphasized in this review include collagen-induced arthritis and antibody-induced arthritis. Collagen-induced arthritis is an example of an active immunization strategy, whereas antibody- induced arthritis models, such as collagen antibody-induced arthritis and K/BxN antibody transfer arthritis, represent examples of passive immunization strategies. The coverage of spontaneous models in this review is focused on the TNFΔ (ARE) mouse, in which arthritis results from overexpression of TNF-α, a master proinflammatory cytokine that drives disease in many patients.
Topics: Animals; Arthritis; Arthritis, Rheumatoid; Collagen; Disease Models, Animal; Inflammation; Mice
PubMed: 26063174
DOI: 10.1177/0300985815588612 -
Nature Reviews. Rheumatology Aug 2017The synovium is the major target tissue of inflammatory arthritides such as rheumatoid arthritis. The study of synovial tissue has advanced considerably throughout the... (Review)
Review
The synovium is the major target tissue of inflammatory arthritides such as rheumatoid arthritis. The study of synovial tissue has advanced considerably throughout the past few decades from arthroplasty and blind needle biopsy to the use of arthroscopic and ultrasonographic technologies that enable easier visualization and improve the reliability of synovial biopsies. Rapid progress has been made in using synovial tissue to study disease pathogenesis, to stratify patients, to discover biomarkers and novel targets, and to validate therapies, and this progress has been facilitated by increasingly diverse and sophisticated analytical and technological approaches. In this Review, we describe these approaches, and summarize how their use in synovial tissue research has improved our understanding of rheumatoid arthritis and identified candidate biomarkers that could be used in disease diagnosis and stratification, as well as in predicting disease course and treatment response.
Topics: Arthritis, Rheumatoid; Biomarkers; Biomedical Research; Humans; Synovial Fluid; Synovial Membrane
PubMed: 28701760
DOI: 10.1038/nrrheum.2017.115 -
Handbook of Experimental Pharmacology 2019Monoclonal antibodies (mAbs) are immunoglobulins designed to target a specific epitope on an antigen. Immunoglobulins of identical amino-acid sequence were originally... (Review)
Review
Monoclonal antibodies (mAbs) are immunoglobulins designed to target a specific epitope on an antigen. Immunoglobulins of identical amino-acid sequence were originally produced by hybridomas grown in culture and, subsequently, by recombinant DNA technology using mammalian cell expression systems. The antigen-binding region of the mAb is formed by the variable domains of the heavy and light chains and contains the complementarity-determining region that imparts the high specificity for the target antigen. The pharmacokinetics of mAbs involves target-mediated and non-target-related factors that influence their disposition.Preclinical safety evaluation of mAbs differs substantially from that of small molecular (chemical) entities. Immunogenicity of mAbs has implications for their pharmacokinetics and safety. Early studies of mAbs in humans require careful consideration of the most suitable study population, route/s of administration, starting dose, study design and the potential difference in pharmacokinetics in healthy subjects compared to patients expressing the target antigen.Of the ever-increasing diversity of therapeutic indications for mAbs, we have concentrated on two that have proved dramatically successful. The contribution that mAbs have made to the treatment of inflammatory conditions, in particular arthritides and inflammatory bowel disease, has been nothing short of revolutionary. Their benefit has also been striking in the treatment of solid tumours and, most recently, as immunotherapy for a wide variety of cancers. Finally, we speculate on the future with various new approaches to the development of therapeutic antibodies.
Topics: Amino Acid Sequence; Animals; Antibodies, Monoclonal; Arthritis; Humans; Immunotherapy; Inflammatory Bowel Diseases; Neoplasms
PubMed: 31820172
DOI: 10.1007/164_2019_323 -
Journal of Orthopaedic Surgery and... Feb 2016Osteoarthritis (OA) is one of the most commonly occurring forms of arthritis in the world today. It is a debilitating chronic illness causing pain and immense discomfort... (Review)
Review
Osteoarthritis (OA) is one of the most commonly occurring forms of arthritis in the world today. It is a debilitating chronic illness causing pain and immense discomfort to the affected individual. Significant research is currently ongoing to understand its pathophysiology and develop successful treatment regimens based on this knowledge. Animal models have played a key role in achieving this goal. Animal models currently used to study osteoarthritis can be classified based on the etiology under investigation, primary osteoarthritis, and post-traumatic osteoarthritis, to better clarify the relationship between these models and the pathogenesis of the disease. Non-invasive animal models have shown significant promise in understanding early osteoarthritic changes. Imaging modalities play a pivotal role in understanding the pathogenesis of OA and the correlation with pain. These imaging studies would also allow in vivo surveillance of the disease as a function of time in the animal model. This review summarizes the current understanding of the disease pathogenesis, invasive and non-invasive animal models, imaging modalities, and pain assessment techniques in the animals.
Topics: Animals; Arthritis, Experimental; Biomarkers; Chronic Pain; Osteoarthritis; Treatment Outcome
PubMed: 26837951
DOI: 10.1186/s13018-016-0346-5 -
Science Immunology Jul 2023Immune checkpoint inhibitor (ICI) therapies used to treat cancer, such as anti-PD-1 antibodies, can induce autoimmune conditions in some individuals. The T cell...
Immune checkpoint inhibitor (ICI) therapies used to treat cancer, such as anti-PD-1 antibodies, can induce autoimmune conditions in some individuals. The T cell mechanisms mediating such iatrogenic autoimmunity and their overlap with spontaneous autoimmune diseases remain unclear. Here, we compared T cells from the joints of 20 patients with an inflammatory arthritis induced by ICI therapy (ICI-arthritis) with two archetypal autoimmune arthritides, rheumatoid arthritis (RA) and psoriatic arthritis (PsA). Single-cell transcriptomic and antigen receptor repertoire analyses highlighted clonal expansion of an activated effector CD8 T cell population in the joints and blood of patients with ICI-arthritis. These cells were identified as CD38CD127 CD8 T cells and were uniquely enriched in ICI-arthritis joints compared with RA and PsA and also displayed an elevated interferon signature. In vitro, type I interferon induced CD8 T cells to acquire the ICI-associated CD38 phenotype and enhanced cytotoxic function. In a cohort of patients with advanced melanoma, ICI therapy markedly expanded circulating CD38CD127 T cells, which were frequently bound by the therapeutic anti-PD-1 drug. In patients with ICI-arthritis, drug-bound CD8 T cells in circulation showed marked clonal overlap with drug-bound CD8 T cells from synovial fluid. These results suggest that ICI therapy directly targets CD8 T cells in patients who develop ICI-arthritis and induces an autoimmune pathology that is distinct from prototypical spontaneous autoimmune arthritides.
Topics: Humans; Arthritis, Psoriatic; Arthritis, Rheumatoid; CD8-Positive T-Lymphocytes; Synovial Fluid; T-Lymphocytes, Cytotoxic
PubMed: 37506196
DOI: 10.1126/sciimmunol.add1591 -
The Medical Clinics of North America May 2017Monoarticular arthritis is inflammation characterized by joint pain, swelling, and sometimes periarticular erythema. Although chronic causes are seen, the onset is often... (Review)
Review
Monoarticular arthritis is inflammation characterized by joint pain, swelling, and sometimes periarticular erythema. Although chronic causes are seen, the onset is often acute. An infected joint can quickly lead to permanent damage, making it a medical emergency. However, acute gout presenting as monoarticular arthritis is often so uncomfortable it requires urgent attention. Monoarticular crystalline arthritis is common and a septic joint is a medical emergency so it is no surprise that these diagnoses come to mind with complaint of inflammation in 1 joint. However, there are many causes of monoarticular arthritis that clinicians must consider.
Topics: Adrenal Cortex Hormones; Arthritis; Arthritis, Infectious; Arthrocentesis; Chondrocalcinosis; Diagnosis, Differential; Gout; Injections, Intra-Articular; Synovitis; Uricosuric Agents; Xanthine Oxidase
PubMed: 28372716
DOI: 10.1016/j.mcna.2016.12.004 -
Radiologic Clinics of North America Sep 2017Ultrasound is currently performed in everyday rheumatologic practice. It is used for early diagnosis, to monitor treatment results, and to diagnose remission. The... (Review)
Review
Ultrasound is currently performed in everyday rheumatologic practice. It is used for early diagnosis, to monitor treatment results, and to diagnose remission. The spectrum of pathologies seen in arthritis with ultrasound includes early inflammatory features and associated complications. This article discusses the spectrum of ultrasound features of arthritides seen in rheumatoid arthritis and other connective tissue diseases in adults, such as Sjögren syndrome, lupus erythematosus, dermatomyositis, polymyositis, and juvenile idiopathic arthritis. Ultrasound findings in spondyloarthritis, osteoarthritis, and crystal-induced diseases are presented. Ultrasound-guided interventions in patients with arthritis are listed, and the advantages and disadvantages of ultrasound are discussed.
Topics: Arthritis; Humans; Joints; Ultrasonography
PubMed: 28774458
DOI: 10.1016/j.rcl.2017.04.005 -
The Orthopedic Clinics of North America Oct 2019
Topics: Adult; Arthritis; Child; Humans
PubMed: 31466670
DOI: 10.1016/j.ocl.2019.06.005