RESUMEN
Axial spondyloarthritis (axSpA) was historically considered a disease of men, largely due to the recognition of a more severe, progressive phenotype, ankylosing spondylitis (AS; or radiographic axSpA, r-axSpA) aiding the clinical diagnosis [1,2]. Data demonstrating the near equal prevalence of axSpA in women only started to emerge in the last decades, highlighting intrinsic differences in disease phenotype, and clinical and imaging characteristics between sexes, which partly explain the issue of underdiagnosis in women. Similar to the evolving understanding of spondyloarthritis and the diseases that term describes, the concepts of gender and sex also warrant further clarification to accurately assess their potential role in disease pathophysiology and phenotypic expression. This narrative review delves into the most recent evidence from the literature on the true prevalence of sex differences in axSpA, and the impact of sex and gender on diagnosis, disease characteristics and treatment response in this, still underserved, chronic disease.
Asunto(s)
Espondiloartritis , Espondilitis Anquilosante , Humanos , Femenino , Masculino , Espondiloartritis/tratamiento farmacológico , Espondilitis Anquilosante/diagnóstico , Espondilitis Anquilosante/epidemiología , Espondilitis Anquilosante/tratamiento farmacológico , PrevalenciaRESUMEN
ABSTRACT: Rheumatoid arthritis (RA) is a chronic, progressive, inflammatory condition that affects about 1% of the world's population. The multifactorial nature of RA has created continuous research discoveries leading to improved identification of specific pathways for the pathogenesis of RA. Improved understanding of the pathways has allowed the development of new targeted drugs. Clinicians must understand the most common pathways for pathogenesis of RA, proper diagnostic techniques, and the appropriate management of this disease given the many possible options at their disposal.
Asunto(s)
Artritis Reumatoide , Artritis Reumatoide/diagnóstico , Artritis Reumatoide/tratamiento farmacológico , HumanosRESUMEN
Numerous pathogenic bacteria produce proteins evolved to facilitate their survival and dissemination by modifying the host environment. These proteins, termed effectors, often play a significant role in determining the virulence of the infection. Consequently, bacterial effectors constitute an important class of targets for the development of novel antibiotics. ExoU is a potent phospholipase effector produced by the opportunistic pathogen Pseudomonas aeruginosa. Previous studies have established that the phospholipase activity of ExoU requires non-covalent interaction with ubiquitin, however the molecular details of the mechanism of activation and the manner in which ExoU associates with a target lipid bilayer are not understood. In this review we describe our recent studies using site-directed spin labeling (SDSL) and EPR spectroscopy to elucidate the conformational changes and membrane interactions that accompany activation of ExoU. We find that ubiquitin binding and membrane interaction act synergistically to produce structural transitions that occur upon ExoU activation, and that the C-terminal four-helix bundle of ExoU functions as a phospholipid-binding domain, facilitating the association of ExoU with the membrane surface.