How Rheumatoid Arthritis Can Result from Provocation of the Immune System by Microorganisms and Viruses

Abstract

The pathogenesis of rheumatoid arthritis (RA), similar to development of a majority of inflammatory and autoimmune disorders, is largely due to an inappropriate or inadequate immune response to environmental challenges. Among these challenges, infectious agents are the undisputed leaders. Since the 1870s, an impressive list of microorganisms suspected of provoking RA has formed, and the list is still growing. Although a definite causative link between a specific infectious agent and the disease has not been established, several arguments support such a possibility. First, in the absence of a defined pathogen, the spectrum of triggering agents may include polymicrobial communities or the cumulative effect of several bacterial/viral factors. Second, the range of infectious episodes (i.e., clinical manifestations caused by pathogens) may vary in the process of RA development from preclinical to late-stage disease. Third, infectious agents might not trigger RA in all cases, but trigger it in a certain subset of the cases, or the disease onset may arise from an unfortunate combination of infections along with, for example, psychological stress and/or chronic joint tissue microtrauma. Fourth, genetic differences may have a role in the disease onset. In this review, two aspects of the problem of “microorganisms and RA” are debated. First, is there an acquired immune deficiency and, in turn, susceptibility to infections in RA patients due to the too frequent and too lengthy infections, which at last break the tolerance of self antigens? Or, second, is there a congenital deficiency in tolerance and inflammation control, which may occur even with ordinary infection frequency and duration?

No effects without causes: the Iron Dysregulation and Dormant Microbes hypothesis for chronic, inflammatory diseases

“…In particular, those recognising relationships between overt chronic, inflammatory disease and the presence of detectable microbes, can highlight that the blood and tissue microbiome is greatly enhanced in these diseases (Alonso et al ., ; Arleevskaya et al ., ; Berstad & Berstad, ; Broxmeyer, , b ; Ebringer, ; Ebringer & Rashid, ; Ebringer, Rashid & Wilson, ; Emery et al ., ; Itzhaki et al ., ; Kell & Kenny, ; Maheshwari & Eslick, ; Miklossy, ; Miklossy & McGeer, ; Pisa et al ., ; Pretorius et al ., ; Pretorius, Bester & Kell, ; Proal et al ., , , ). We note too that while it is all too easy to dismiss such findings as ‘contaminants’, those doing so must also explain why the microbes appear at much higher levels only in the ‘disease’ samples.…”

Impact of Premorbid Infection on Onset and Disease Activity of Rheumatoid Arthritis

“…Although a definite causative link between a specific infectious agent and the disease has not been established, several arguments support such a possibility. First, in the absence of a certain pathogen, the spectrum of microorganisms involved in triggering RA may include poly-microbial communities or the cumulative effect of bacterial or virus factors [3]. Secondly, infections didn’t lead to RA in all cases, but initiate it in a certain subset of patients who was born with a genetic susceptibility [4-7].…”

Ly6Chigh monocytes facilitate transport of Murid herpesvirus 68 into inflamed joints of arthritic mice

“…The involvement of viruses in the pathogenesis of rheumatoid arthritis (RA) has long been suspected to exacerbate severity of symptoms . For many years EBV was a suspected cause of relapses in arthritis based on several evidence that link the virus and RA .…”

“…The involvement of viruses in the pathogenesis of rheumatoid arthritis (RA) has long been suspected to exacerbate severity of symptoms [1]. For many years EBV was a suspected cause of Monocytes are essential to regulate both homeostasis and inflammation and to control effective clearance of microbial infections.…”