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Arthritis Care & Research Apr 2024Giant cell arteritis (GCA) is characterized by granulomatous inflammation of the medium- and large-sized arteries accompanied by remodeling of the vessel wall....
OBJECTIVE
Giant cell arteritis (GCA) is characterized by granulomatous inflammation of the medium- and large-sized arteries accompanied by remodeling of the vessel wall. Fibroblast activation protein alpha (FAP) is a serine protease that promotes both inflammation and fibrosis. Here, we investigated the plasma levels and vascular expression of FAP in GCA.
METHODS
Plasma FAP levels were measured with enzyme-linked immunosorbent assay in treatment-naive patients with GCA (n = 60) and polymyalgia rheumatica (PMR) (n = 63) compared with age- and sex-matched healthy controls (HCs) (n = 42) and during follow-up, including treatment-free remission (TFR). Inflamed temporal artery biopsies (TABs) of patients with GCA (n = 9), noninflamed TABs (n = 14), and aorta samples from GCA-related (n = 9) and atherosclerosis-related aneurysm (n = 11) were stained for FAP using immunohistochemistry. Immunofluorescence staining was performed for fibroblasts (CD90), macrophages (CD68/CD206/folate receptor beta), vascular smooth muscle cells (desmin), myofibroblasts (α-smooth muscle actin), interleukin-6 (IL-6), and matrix metalloproteinase-9 (MMP-9).
RESULTS
Baseline plasma FAP levels were significantly lower in patients with GCA compared with patients with PMR and HCs and inversely correlated with systemic markers of inflammation and angiogenesis. FAP levels decreased even further at 3 months on remission in patients with GCA and gradually increased to the level of HCs in TFR. FAP expression was increased in inflamed TABs and aorta of patients with GCA compared with control tissues. FAP was abundantly expressed in fibroblasts and macrophages. Some of the FAP fibroblasts expressed IL-6 and MMP-9.
CONCLUSION
FAP expression in GCA is clearly modulated both in plasma and in vessels. FAP may be involved in the inflammatory and remodeling processes in GCA and have utility as a target for imaging and therapeutic intervention.
PubMed: 38685696
DOI: 10.1002/acr.25354 -
Rheumatic Diseases Clinics of North... May 2024Since their introduction, immune checkpoint inhibitors have revolutionized cancer treatment by harnessing the body's own immune system as a defense against tumor growth.... (Review)
Review
Since their introduction, immune checkpoint inhibitors have revolutionized cancer treatment by harnessing the body's own immune system as a defense against tumor growth. The downside of activating the immune system is the development of immune-related adverse events (irAEs), which mimic autoimmune disease of various organ systems. The musculoskeletal system is an uncommon, but substantial one for patients and can lead to long-term pain and disability that affects their quality of life. This review summarizes recent literature on imaging forms utilized for diagnosis and assessing treatment response in rheumatic irAEs.
Topics: Humans; Rheumatic Diseases; Immune Checkpoint Inhibitors; Magnetic Resonance Imaging
PubMed: 38670729
DOI: 10.1016/j.rdc.2024.02.005 -
Rheumatic Diseases Clinics of North... May 2024Immune checkpoint inhibitors (ICIs) have revolutionized cancer treatment through blocking immunoregulatory pathways, resulting in augmented antitumor responses. However,... (Review)
Review
Immune checkpoint inhibitors (ICIs) have revolutionized cancer treatment through blocking immunoregulatory pathways, resulting in augmented antitumor responses. However, ICIs can cause inflammatory autoimmune toxicities, known as immune-related adverse events (irAEs). Common rheumatic irAEs include inflammatory arthritis, polymyalgia rheumatica-like symptoms, and myositis. Fewer cases of de novo connective tissue disease as irAEs have been described and have mainly presented with cutaneous manifestations of systemic lupus erythematosus (SLE) and systemic sclerosis (SSc). Treatments include glucocorticoids and steroid-sparing agents such as hydroxychloroquine, mycophenolate mofetil, and methotrexate with improvement of symptoms. In this review, the authors discuss immune-related SLE and SSc and their management.
Topics: Humans; Immune Checkpoint Inhibitors; Connective Tissue Diseases; Scleroderma, Systemic; Lupus Erythematosus, Systemic; Glucocorticoids
PubMed: 38670728
DOI: 10.1016/j.rdc.2024.01.007 -
Rheumatic Diseases Clinics of North... May 2024The introduction of immune checkpoint inhibitors (ICIs) has changed the landscape of the treatment of cancer. Several immune-related adverse events (irAEs) have now been... (Review)
Review
The introduction of immune checkpoint inhibitors (ICIs) has changed the landscape of the treatment of cancer. Several immune-related adverse events (irAEs) have now been described such as ICI-inflammatory arthritis (IA), sicca syndrome, polymyalgia rheumatica, myositis, and vasculitis as a consequence of immune activation. The onset of the ICI-IA can vary from after the first infusion of ICIs to a delayed presentation a year or more after ICI initiation. Ultimately, baseline patient and tumor characteristics, the types of immunotherapies used, pre-existing autoimmune diseases, and/or other irAEs, as well as patient preferences will all shape the discussions around ICI-IA management.
Topics: Humans; Immune Checkpoint Inhibitors; Arthritis; Neoplasms; Immunotherapy
PubMed: 38670725
DOI: 10.1016/j.rdc.2024.02.002 -
Rheumatic Diseases Clinics of North... May 2024Polymyalgia rheumatica (PMR) immune-related adverse events (ICI-PMRs) represent a novel, distinct entity, despite many clinical, laboratory, and imaging similarities to... (Review)
Review
Polymyalgia rheumatica (PMR) immune-related adverse events (ICI-PMRs) represent a novel, distinct entity, despite many clinical, laboratory, and imaging similarities to classical PMR. Important questions remain in differentiating ICI-PMR from classical PMR, as well as other immune-related adverse events and PMR mimics. Despite this, ICI-PMR currently takes treatment cues from classical PMR, albeit with considerations relevant to cancer immunotherapy. Comparisons between ICI-PMR and classical PMR may provide further bidirectional insights, especially given that important questions remain unanswered about both diseases. The cause of classical PMR remains poorly understood, and ICI-PMR may represent a model of induced PMR, with important therapeutic implications.
Topics: Polymyalgia Rheumatica; Humans; Immune Checkpoint Inhibitors
PubMed: 38670724
DOI: 10.1016/j.rdc.2024.02.001 -
Rheumatic Diseases Clinics of North... May 2024Immune checkpoint inhibitors (ICIs) have greatly improved survival of several cancers with historically very poor prognosis. ICIs act by stimulating the patient's own... (Review)
Review
Immune checkpoint inhibitors (ICIs) have greatly improved survival of several cancers with historically very poor prognosis. ICIs act by stimulating the patient's own immune system to fight cancer. Simultaneously, this immune activation can lead to immune-related adverse events (irAEs), including rheumatic manifestations (Rh-irAEs). Rh-irAEs mimic primary rheumatic diseases including arthritis, polymyalgia rheumatica, myositis, vasculitis, sarcoidosis, and sicca. This article summarizes the latest evidence regarding the utility of laboratory investigations in Rh-irAEs.
Topics: Humans; Rheumatic Diseases; Immune Checkpoint Inhibitors; Neoplasms
PubMed: 38670720
DOI: 10.1016/j.rdc.2024.01.003 -
Rheumatology Advances in Practice 2024
PubMed: 38650634
DOI: 10.1093/rap/rkae047 -
Annals of Internal Medicine May 2024Many patients with rheumatologic conditions receive care from physicians other than rheumatologists. Here we note key findings from 6 studies in rheumatology published... (Review)
Review
Many patients with rheumatologic conditions receive care from physicians other than rheumatologists. Here we note key findings from 6 studies in rheumatology published in 2023 that offer valuable insights for internal medicine specialists and subspecialists outside of rheumatology. The first study investigated the effect of low-dose glucocorticoids on patients with rheumatoid arthritis (RA) over 2 years and challenged existing perceptions about the risks of glucocorticoids in this setting. The second study focused on the updated guideline for preventing and treating glucocorticoid-induced osteoporosis. With the chronic and widespread use of glucocorticoids, the American College of Rheumatology emphasized the importance of assessing fracture risk and initiating pharmacologic therapy when appropriate. The third study explored the potential use of methotrexate in treating inflammatory hand osteoarthritis, suggesting a novel approach to managing this challenging and common condition. The results of the fourth article we highlight suggest that sarilumab has promise as an adjunct treatment of polymyalgia rheumatica relapse during glucocorticoid dosage tapering. The fifth study evaluated sublingual cyclobenzaprine for fibromyalgia treatment, noting both potential benefits and risks. Finally, the sixth article is a systematic review and meta-analysis that assessed the therapeutic equivalence of biosimilars and reference biologics in the treatment of patients with RA. Knowledge of this recent literature will be useful to clinicians regardless of specialty who care for patients with these commonly encountered conditions.
Topics: Humans; Glucocorticoids; Osteoporosis; Arthritis, Rheumatoid; Antirheumatic Agents; Methotrexate; Rheumatology; Rheumatic Diseases; Biosimilar Pharmaceuticals; Polymyalgia Rheumatica; Fibromyalgia
PubMed: 38621248
DOI: 10.7326/M24-0678 -
Acta Medica Portuguesa May 2024
Topics: Humans; Polymyalgia Rheumatica; COVID-19 Vaccines; Male; Female; Aged; Databases, Factual; COVID-19; Middle Aged
PubMed: 38607657
DOI: 10.20344/amp.20952 -
Best Practice & Research. Clinical... Apr 2024Giant cell arteritis (GCA) is a prototypic autoimmune disease with a highly selective tissue tropism for medium and large arteries. Extravascular GCA manifests with... (Review)
Review
Giant cell arteritis (GCA) is a prototypic autoimmune disease with a highly selective tissue tropism for medium and large arteries. Extravascular GCA manifests with intense systemic inflammation and polymyalgia rheumatica; vascular GCA results in vessel wall damage and stenosis, causing tissue ischemia. Typical granulomatous infiltrates in affected arteries are composed of CD4 T cells and hyperactivated macrophages, signifying the involvement of the innate and adaptive immune system. Lesional CD4 T cells undergo antigen-dependent clonal expansion, but antigen-nonspecific pathways ultimately control the intensity and duration of pathogenic immunity. Patient-derived CD4 T cells receive strong co-stimulatory signals through the NOTCH1 receptor and the CD28/CD80-CD86 pathway. In parallel, co-inhibitory signals, designed to dampen overshooting T cell immunity, are defective, leaving CD4 T cells unopposed and capable of supporting long-lasting and inappropriate immune responses. Based on recent data, two inhibitory checkpoints are defective in GCA: the Programmed death-1 (PD-1)/Programmed cell death ligand 1 (PD-L1) checkpoint and the CD96/CD155 checkpoint, giving rise to the "lost inhibition concept". Subcellular and molecular analysis has demonstrated trapping of the checkpoint ligands in the endoplasmic reticulum, creating PD-L1 CD155 antigen-presenting cells. Uninhibited CD4 T cells expand, release copious amounts of the cytokine Interleukin (IL)-9, and differentiate into long-lived effector memory cells. These data place GCA and cancer on opposite ends of the co-inhibition spectrum, with cancer patients developing immune paralysis due to excessive inhibitory checkpoints and GCA patients developing autoimmunity due to nonfunctional inhibitory checkpoints.
PubMed: 38599937
DOI: 10.1016/j.berh.2024.101943