title: Major involvement of bacterial components in rheumatoid arthritis and its accompanying oxidative stress, systemic inflammation and hypercoagulability.
abstract: We review the evidence that infectious agents, including those that become dormant within the host, have a major role to play in much of the etiology of rheumatoid arthritis and the inflammation that is its hallmark. This occurs in particular because they can produce cross-reactive (auto-)antigens, as well as potent inflammagens such as lipopolysaccharide that can themselves catalyze further inflammagenesis, including via β-amyloid formation. A series of observables coexist in many chronic, inflammatory diseases as well as rheumatoid arthritis. They include iron dysregulation, hypercoagulability, anomalous morphologies of host erythrocytes, and microparticle formation. Iron dysregulation may be responsible for the periodic regrowth and resuscitation of the dormant bacteria, with concomitant inflammagen production. The present systems biology analysis benefits from the philosophical idea of "coherence," that reflects the principle that if a series of ostensibly unrelated findings are brought together into a self-consistent narrative, that narrative is thereby strengthened. As such, we provide a coherent and testable narrative for the major involvement of (often dormant) bacteria in rheumatoid arthritis.
authors.affiliation: 1 Department of Physiology, Faculty of Health Sciences, University of Pretoria, Arcadia, Pretoria 0007, South Africa.
authors.forename: Etheresia
authors.initials: E
authors.lastname: Pretorius
authors.affiliation: 1 Department of Physiology, Faculty of Health Sciences, University of Pretoria, Arcadia, Pretoria 0007, South Africa.
authors.forename: Oore-Ofe
authors.initials: OO
authors.lastname: Akeredolu
authors.affiliation: 1 Department of Physiology, Faculty of Health Sciences, University of Pretoria, Arcadia, Pretoria 0007, South Africa.
authors.forename: Prashilla
authors.initials: P
authors.lastname: Soma
authors.affiliation: 2 School of Chemistry, The University of Manchester, Manchester, M13 9PL, UK.|3 The Manchester Institute of Biotechnology, The University of Manchester, Manchester, M1 7DN, UK.|4 Centre for Synthetic Biology of Fine and Speciality Chemicals, The University of Manchester, Manchester, M1 7DN, UK.
authors.forename: Douglas B
authors.initials: DB
authors.lastname: Kell
mesh_terms: D001172:Arthritis, Rheumatoid / Q000209:etiology / Q000276:immunology / Q000382:microbiology*; D001324:Autoantigens / Q000276:immunology*; D055252:Cell-Derived Microparticles / Q000276:immunology*; D005260:Female; D006801:Humans; D007249:Inflammation / Q000276:immunology; D008070:Lipopolysaccharides / Q000276:immunology; D008297:Male; D008875:Middle Aged; D018384:Oxidative Stress / Q000276:immunology / Q000502:physiology; D011511:Proteus / Q000276:immunology*; D011512:Proteus Infections / Q000382:microbiology / Q000473:pathology*; D019851:Thrombophilia / Q000276:immunology / Q000382:microbiology*; D014552:Urinary Tract Infections / Q000382:microbiology / Q000473:pathology*
chemical_list: D001324:Autoantigens; D008070:Lipopolysaccharides
keywords: Proteus; Rheumatoid arthritis; atopobiosis; comorbidities; dormancy; infectious agents; inflammation; iron dysregulation; lipopolysaccharides