Moreover, the finding of Rasmussens aneurysms in inflamed arteries near tuberculosis cavities in the lung parenchyma of patients with pulmonary TB , together with the high frequency of tuberculin skin test positivity in TAK patients  further support this hypothesis. composition with PTX-3 levels in healthy individuals and in patients with TAK or with other vasculitides. 4. Infections and TAK A link between TAK and infections has long been considered. In fact, in his case report, Takayasu emphasized that he and his colleagues did not find evidence of infections, such as tuberculosis (TB) or syphilis . A putative association between TAK and latent and active TB was first proposed based on the findings of granulomas-like lesions in affected arteries of patients with TAK, which histologically resembled granulomas found in tuberculosis . Further epidemiological and clinical studies reporting higher frequency of TB in patients with TAK, compared with the general population, also suggest a possible causal association between these two diseases . Moreover, the finding of Rasmussens aneurysms in inflamed arteries near tuberculosis cavities in the lung parenchyma of patients with pulmonary TB , together with the high frequency of tuberculin skin test positivity in TAK patients  further support this hypothesis. A more suggestive link between TB and TAK was the discovery that IS6110 and HupB gene sequences of are frequently detectable in formalin fixed aortic specimens of patients with TAK, indicating the possibility that the vascular lesions of TAK could be a clinical manifestation of extra-pulmonary tuberculosis . Nevertheless, other studies failed to demonstrate a link between TB and TAK. For example, in a study using using the Quantiferon-TB Gold test (QFT), an in vitro assay measuring interferon-gamma (IFN-) response to mTB antigens and helpful in diagnosing latent TB infection, QFT positivity was similar between TAK patients and controls . It must be noted, however, that in the same Mouse monoclonal to GCG study, tuberculin positivity was higher in the TAK group than in controls and whereas only one control had a history of previous TB infection, six TAK patients had previous TB history. In addition, it is unknown if the fact that TAK patients were older that control may have affected the IFN- response in this study . Moreover, Arnaud et al. did not detect the presence of complex RNA in arterial lesions of fresh arterial samples obtained from TAK patients, after being assessed by three different methods: Acid fast and auramine-fluorochrome staining, mycobacterial cultures, and nucleic acid amplification. Although the authors did not rule out the likelihood of a cross-reaction between mycobacterial and arterial antigens . Similarly, whereas IS6110 sequence was found in peripheral blood from 78% patients with pulmonary tuberculosis, all samples from patients with TAK were negative TAK 259 for the insertion sequence IS6110 and for HSP65 and 16S rRNA genes . The above data indicate that although there are various pieces of evidence that implicate mTB with TAK, confirmatory studies are needed to establish a direct causal association between this pathogen and TAK. Future studies, using large number of patients are needed to establish the existence of causal relationship between TAK and mTB. In addition to the proposed causal role of mTB, other microorganisms including and have been investigated in association with TAK, although there is no convincing evidence to support a potential association of any of these pathogens with TAK . Intriguingly, in some patients, TAK is associated TAK 259 with sarcoidosis [28,73], a multisystem disorder of unknown etiology characterized by non-necrotizing granulomas composed of infiltrating T-lymphocytes, mononuclear phagocytes in affected tissues. Although the etiology of sarcoidosis is largely unknown, the involvement of a pathogen-triggered autoimmune reaction has been proposed [74,75] and TAK 259 thus the concurrence of both diseases in some patients suggest the potential existence of overlapping mechanisms in the pathogenesis of these diseases . On the other hand, the coexistence of TAK with ulcerative colitis, an inflammatory bowel disease TAK 259 associated with particular genetic background and alterations in the gut microbiota composition, has been frequently reported in the literature [76,77]. was recently documented in patients with cutaneous vasculitis and TAK , however, it is unclear if those findings are representative of TAK or if they are an atypical finding since patients reported in that study also presented with Cogans syndrome . In preclinical models of vasculitis, dendritic cells at the media-adventitia junction of medium and large arteries were identified as dominant pathogen sensors that recognize TAK 259 stimuli via TLR2 and TLR4 pathways that ultimately render the vessel wall susceptible to immunological attack.