Lyme disease, caused by the spirochete Borrelia burgdorferi, is the most prevalent arthropod-borne illness in the United States and remains a clinical and social challenge. The spectrum of disease severity among infected patients suggests that host genetics contribute to pathogenic outcomes, particularly in patients who develop arthritis. Using a forward genetics approach, we identified the lysosomal enzyme β-glucuronidase (GUSB), a member of a large family of coregulated lysosomal enzymes, as a key regulator of Lyme-associated arthritis severity. Severely arthritic C3H mice possessed a naturally occurring hypomorphic allele, Gusbh. C57BL/6 mice congenic for the C3H Gusb allele were prone to increased Lyme-associated arthritis severity. Radiation chimera experiments revealed that resident joint cells drive arthritis susceptibility. C3H mice expressing WT Gusb as a transgene were protected from severe Lyme arthritis. Importantly, the Gusbh allele also exacerbated disease in a serum transfer model of rheumatoid arthritis. A known GUSB function is the prevention of lysosomal accumulation of glycosaminoglycans (GAGs). Development of Lyme and rheumatoid arthritis in Gusbh-expressing mice was associated with heightened accumulation of GAGs in joint tissue. We propose that GUSB modulates arthritis pathogenesis by preventing accumulation of proinflammatory GAGs within inflamed joint tissue, a trait that may be shared by other lysosomal exoglycosidases.
Objectives: To update the first-line conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) prescribing pattern, describe change and variation across demographical and geographical factors in the Rheumatoid arthritis (RA) population, and identify individual and hospital factors associated with it.
Methods: This retrospective cohort study included newly diagnosed RA adult patients from 1 May 2018-1 April 2023 in the UK. We used adjusted multinomial logistic regression with random effect to explore associations with different first-line csDMRAD prescription and to account for hospital-level clustering.
Department of Rheumatology, Erasmus Medical Center, Rotterdam, Netherlands; Department of Rheumatology, Leiden University Medical Center, Leiden, Netherlands.
Background: About 20% of patients with rheumatoid arthritis on disease-modifying antirheumatic drugs (DMARDs) can reach sustained DMARD-free remission. Nonetheless, the 2022 EULAR recommendations discourage complete cessation of DMARDs due to flare risk. The evidence behind this recommendation is obtained from trial populations using biological DMARDs, representing only a subgroup of the total population of patients with rheumatoid arthritis.
Department of Internal Medicine III, Division of Rheumatology, Medical University of Vienna, 1090 Vienna, Austria; Division of Rheumatology, Department of Medicine-Solna, Karolinska Institute, Stockholm, Sweden. Electronic address:
Department of Medicine, Division of Rheumatology, Queen's University, Kingston, Ontario, Canada; Faculty of Health Sciences, School of Medicine, Queen's University, Kingston, Ontario, Canada; Translational Institute of Medicine, Department of Medicine, Queen's University, Ontario, Canada; Rheumatology Clinic, Kingston Health Science Centre, Kingston, Ontario, Canada. Electronic address:
Introduction: Joint tissues affected by inflammatory arthritis (IA) create hypoxic microenvironments that sustain the inflammatory response. Although targeting molecules in hypoxia-induced pathways has provided valuable insights into potential novel therapies for various types of IA, progress remains preclinical, and no clinical trials have been conducted for IA.
Methods: A literature search was conducted to create a narrative review exploring the role of hypoxia and its signaling pathways in IA pathogenesis, as well as the potential and future directions for IA therapies that target hypoxia-induced molecules before moving forward to clinical applications.
