title: Rampant infections of bone marrow stem cell niches as triggers for spondyloarthropathies and rheumatoid arthritis.
abstract: Tropheryma Whipplei can induce rheumatism mimicking SpA or RA, but even more rampant bacterial/viral infections in epiphyseal bones could also contribute to the onset of RA and SpA. Indeed, as bone marrow stem cell niches are enriched in Tregs and myeloid derived suppressor cells, these areas are favourable for the persistence of quiescent viruses and/or dormant bacteria. This review focuses on the possibility that such silent infections of bone marrow stem cell niches might contribute to the pathogenesis of SpA and RA, at least during their onset. Some infections can affect the bone marrow mesenchymal stem cells, which can transmit these pathogens to their progeny. Transient but repeated revivals of viruses or dormant bacteria could promote the conversion of marrow regulatory T cells into effector phenotypes, leading to autoimmunity in the epiphyseal bone marrow, entheses and adjacent synovium. This scenario would also fit the flares of rheumatic disorders and explain why some joints or enthuses can be severely involved whereas their neighbours remain intact. The efficiency of anti-TNF drugs does not rule out a role of persistent infections in SpA and RA. These drugs do not affect chlamydial clearance, or the reactivation of latent Salmonella enterica serovar Typhimurium in mice or Epstein-Barr virus in humans. Anti-TNF might even prevent, rather than foster, the revival of dormant bacteria and viruses in marrow stem cell niches. Indeed, anti-TNF enhance the maturation of the immunosuppressive immature myeloid cells around stem cells into dendritic cells and macrophages, thus restoring immune responses in these areas.
authors.affiliation: Rheumatology Unit, Nantes University Hospital, CHU Nantes, France. jeanmarie.berthelot@chu-nantes.fr.
authors.forename: Jean-Marie
authors.initials: JM
authors.lastname: Berthelot
authors.affiliation: Department of Rheumatology, Reference Center for Rare Autoimmune Diseases, Division of Internal Medicine, Hautepierre Hospital, University Hospital of Strasbourg, France.
authors.forename: Jean
authors.initials: J
authors.lastname: Sibilia
mesh_terms: D000818:Animals; D001172:Arthritis, Rheumatoid / Q000209:etiology*; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000382:microbiology* / Q000821:virology*; D051379:Mice; D000069283:Rituximab / Q000494:pharmacology; D025242:Spondylarthropathies / Q000209:etiology*; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors
chemical_list: D014409:Tumor Necrosis Factor-alpha; D000069283:Rituximab