For autoimmune

MI-503 ic50 illnesses in which the causative organism has been identified, molecular mimicry is a part of the etiology.[3, 4] For autoimmune rheumatic illness, molecular mimicry has been proposed as an initiating factor for autoimmunity.[5] There are accumulating data that the gut microbiome has a role in induction or activation of Th17 T helper cells and Treg cells, either of which might have a role in autoimmune diseases. Segmented, filamentous bacteria have a fundamental role in the development of Th17 cells.[6] Meanwhile, gut helminths up-regulate regulatory T cells[7] and instillation of helminths can ameliorate diseases in animal models of type 1 diabetes, multiple sclerosis, inflammatory bowel disease, rheumatoid arthritis or systemic lupus erythematosus.[7] Early stage human trials of helminthes for inflammatory bowel disease have been undertaken.[8] Whether there are specific or only non-specific effects of the microbiome on autoimmune diseases, or whether

any such effects are active or bystander, remains to be determined. Evidence has accumulated that oral flora may be critical in the pathogenesis of rheumatoid arthritis and that molecular mimicry may be the mechanism (reviewed in Bingham and Moni).[9] Since the initial description of antibodies binding citrillunated peptides Trichostatin A in the sera of rheumatoid arthritis patients by Walter van Venrooij and his colleagues,[10] the presence of these antibodies (anti-CCP) have become an important part of the diagnostic procedure in this disease, and Interleukin-3 receptor may well be involved in the pathogenesis of joint destruction.[11] On the basis of expression of the enzyme peptidylarginine deiminase, which converts arginine to citrulline when part of a polypeptide and the epidemiological association of rheumatoid arthritis with periodontal disease, Porphyromonas gingivalis, the only bacteria to possess this enzyme, was proposed as an etiological agent in rheumatoid arthritis almost a decade ago.[12] Since then, a large body of data has accumulated suggesting an initial immune response to citrullinated peptides

produced by P. gingivalis leads to an autoimmune response to several citrullinated self-proteins, and that such an autoimmune response may underlie the pathogenesis of rheumatoid arthritis (reviewed in Bingham and Moni[9] and Moeez and Bhatti,[11] see Quirke et al.[13] Rohner et al.[14] and Wegner et al.[15] for recent data). Antibodies to P. gingivalis-citrullinated peptides are also found in subjects at risk for rheumatoid arthritis by virtue of human leukocyte antigen (HLA) genetics or family history.[16-18] Among 284 subjects with rheumatoid arthritis-risk HLA alleles or a family history of the disease, 117 were rheumatoid factor or anti-CCP positive. This positivity was associated with antibodies binding P. gingivalis.