A1.50 Extrathymic autoimmune regulator (AIRE) expression in rheumatoid arthritis synovial tissue

Background Autoimmune Regulator (AIRE) is a transcription factor that is involved in the negative selection of self-reactive thymocytes in the thymus and therefore is pivotal in the establishment of central tolerance. Recently, AIRE has also been detected in secondary (or peripheral) lymphoid organs. In these secondary lymphoid organs, AIRE was found to regulate the expression of a group of tissue-specific antigens that is distinct from those expressed in the thymus, suggesting that extrathymic AIRE may play a complementary role in tolerance induction. It is currently unknown whether AIRE may also play a role in human chronically inflamed synovial tissue (ST) that sometimes contains ectopic lymphoid neogenesis (ELN). Objective To study whether extrathymic AIRE-expressing cells (eTACs) are present in ST of osteoarthritis (OA), psoriatic arthritis (PsA) or or rheumatoid arthritis (RA) patients with or without ELN. Methods ST was obtained via mini-arthroscopy from inflamed joints of OA, PsA or RA patients. Presence of AIRE protein was detected in ST cryosections by immunofluorescence staining and evaluated by confocal microscopy. Results ST from OA and PsA patients did not contain eTACs. Interestingly, eTACs were detected in some RA patients, but only in ST containing ELN. In these tissues eTACs were mainly found in large aggregates in the proximity of B-cells. The exact phenotype of eTACs in RA ST and their precise role in ELN are currently further investigated in our lab. Conclusion We demonstrate for the first time that eTACs can be found in chronic inflammation, more specifically in RA ST containing ELN. The presence of eTACs in RA ST may be an attempt to control inflammation through the induction of peripheral tolerance to antigens involved in the perpetuation of the inflammatory response. Eventually, advanced understanding of the function of eTACs in synovial inflammation may be exploited to develop new treatment modalities for RA patients.