gingivalisdirectly promotes early and later stages of apoptosis of human chondrocytes, which may contribute to the cartilage loss in RA patients [88]

gingivalisdirectly promotes early and later stages of apoptosis of human chondrocytes, which may contribute to the cartilage loss in RA patients [88]. == Conclusion == RA is a complex autoimmune inflammatory disease. pathogenesis are not fully understood. It is believed that approximately half of the risk factors for RA are attributed to genetic factors such as the human leukocyte antigen (HLA) alleles while the other half of the risks are environmental factors including infection and smoking [2]. Clinical and animal model studies have suggested that infections by many microorganisms, such asPorphyromonas gingivalis(P. gingivalis),Proteus mirabilis(P. mirabilis), EpsteinBarr virus (EBV), and mycoplasma contribute to the etiopathogenesis of RA (Table 1). == Table 1. == Common RA-associated microbes. For this review, we first identified the most common microbial infections associated to RA SU-5402 in the literature [35] and then performed a key word search using arthritis and name of the microorganism for original publications in English in the databases including Pubmed/Medline, Embase, EBSCO, SCOPUS, and Cochrane Library till November, 2013. The candidate microorganisms included in our search wereP. gingivalis, P. mirabilis, EBV, cytomegalovirus (CMV), human immunodeficiency virus (HIV), parvovirus, hepatitis virus, herpes virus, human T-lymphotropic virus 1 (HTLV-1), mycoplasma,Streptococcus pyogenes(S. pyogenes), Salmonella, mycobacterium, and enterobacterium. Thus, this SU-5402 review will discuss studies regarding to those microorganisms with RA and emphasize onP. gingivaliswhich shows the strongest association with RA. Our discussion is organized in three sections, namely, clinical association of infection with RA, induction of arthritis by infection in animal models, and the pathogenic mechanisms of infection in RA. == Clinical Association of Infection with RA == == Clinical co-existence of infection and RA == Periodontal disease (PD) is the most commonly associated RA disease. The association between the two has been considered since the early 1820s. PD is caused by chronic infection of approximately twenty different bacterial species, of whichP. gingivalis, Prevotella intermedia, Tannerella forsythia,andAggregatibacter actinomycetemcomitansare the most common ones. PD can progress from gingivitis to periodontitis and cause bone degeneration in the jaw. Clinical association studies consistently show that the prevalence of periodontitis is increased about two-fold in RA patients than non-RA patients. In a large study involving 4461 participants aged 60 or older in the US population, subjects with RA were more likely to have periodontitis (odds ratio (OR)=1.82) or complete tooth loss (edentulism, OR=2.27), compared to non-RA subjects after adjusting for age, gender, race/ethnicity, and Rabbit polyclonal to TrkB smoking [6]. Another study reported that moderate to severe periodontitis was more prevalent in RA patients (51%) than age and gender matched osteoarthritis patients (26%) [7]. A recent study in the Dutch population confirmed the higher prevalence of severe periodontitis in RA patients [8]. They also reported that RA patients with SU-5402 severe periodontitis had higher DAS28 scores than RA patients with no or moderate periodontitis, suggesting that the severity of periodontitis is related to the severity of RA [8]. However, it is less clear that whether subjects with PD have increased incidence of RA. In a large prospective study involving 81,132 American women in the Nurses Health Study cohort, there is no increased risk of later-onset RA in subjects with a history of periodontal surgery and/ or tooth loss compared to subjects with healthy periodontal conditions [9]. In another large prospective study using the National Health and Nutrition Examination Survey cohort, subjects with PD experienced higher odds of prevalent/incident RA, but most odd ratios were not statistically significant [10]. It is also important to keep in mind that both studies are not specifically designed to examine the relationship between PD and RA. It is quite possible that there are missing data about PD and RA status in these cohorts and differential RA and PD ascertainment bias may also complicate the interpretation of data. Taken together, clinical studies have clearly shown the association of periodontal infection with RA. However, more longitudinal studies using well-defined populations are necessary to support the conclusion that periodontal infection is a risk factor for the development of RA. Another common infection associated with RA isProteus-caused urine tract infection. Patients with RA had significantly increased incidence of urinary tract infection and subclinical/asymptomatic bacteriuria compared to non-RA subjects [11].P. mirabilisbacteria were isolated at a higher rate from urine samples of both female (63%) and male (50%) patients with RA than from healthy female (3235%) and male (711%) subjects and patients with other autoimmune diseases including osteoarthritis, fibromyalgia, and psoriasis [12]. These studies implicate a plausible role ofProteusmicroorganisms in the development of RA. Furthermore, it has been well documented.