AB0071 Analysis of synovial expression of parvovirus B19 assessed immunohistochemically and correlated to synovitis score

M Tarasovs, A Kadisa, A Mihailova, S Skuja, M Murovska, V Groma
2017 Abstracts Accepted for Publication   unpublished
Scientific Abstracts 1071 (IDO1) expression was analysed by Western Blot and expression of enzymes of the kynurenine pathway by real-time PCR. Tryptophan/ kynurenine levels in culture supernatants were quantified by HPLC. Results: SF strongly inhibited the proliferation of co-cultured Th cells. Tryptophan was completely depleted within a few days in co-cultures of SF and Th cells, resulting in eukaryotic initiation factor (eIF)2α phosphorylation, TCRζ-chain downregulation and proliferation
more » ... proliferation arrest. Blocking of IDO1 completely restored Th cell proliferation, indicating that SF suppressed the proliferation of Th cells through IDO1-mediated tryptophan catabolism. Interestingly, RASF showed a significantly lower IDO1 expression, tryptophan metabolism and a weaker Th cell suppressive capacity compared to OASF. Under hypoxic conditions, the secretion of IFNg, the expression of IDO1, the tryptophan metabolism and the Th cell suppressive capacity of both OASF and RASF were significantly reduced. Conclusions: SF suppressed Th cell growth through IDO1-mediated tryptophan catabolism. This mechanism may play an important role in preventing inappropriate Th cell responses under normal conditions. The reduced tryptophan metabolism under hypoxia together with the inferior efficiency of RASF to restrict T cell proliferation likely supports the development of synovitis in RA.
doi:10.1136/annrheumdis-2017-eular.6411 fatcat:g6ukndcscfakfg5e2flq7zcxdq