The role of free endosomal epitopes in the mechanisms of amelioration and flares of rheumatoid arthritis-associated conditions: pregnancy and infective hepatitis

Innocenzo Caruso, Enzo Massimo Caruso, Salvatore Santandrea, Franco Montrone, Piercarlo Sarzi Puttini, Marco Cazzola
2018 Translational Medicine Communications  
It is known that rheumatoid symptoms improve in pregnancy and in patients who develop infective jaundice. The mechanism of amelioration might involve the direct interaction of free endosomal self-epitopes that are released by the cells of the involved organ with antigen binding sites on the membranes of anti-idiotypic cells, resulting in possible suppressive effects. Methods: Immune responses of peripheral blood mononuclear cells (PBMCs) to longstanding synovial fluid (SFMC or primary
more » ... r primary ultrafiltrate) and to the endosomal extracts enriched with self-epitope-receptor microcomplexes (MICs) were investigated. The MICs (secondary ultrafiltrate) were prepared from PBMCs that were previously cultured with SFMC ultrafiltrates and had therefore been in contact with large number of self-epitopes. Results: Addition of primary ultrafiltrate to PBMCs elicited significant expansion of regulatory T cells (CTLA-4+CD4 +CD25+), and reduction of CD69+CD4+CD25+ cells. In contrast, secondary ultrafiltrate, which contains the microcomplexes, produced an inflammatory response, with CD69+ cells increasing to 47% of CD4+CD25+ cells. This opposite response indicated that, in all likelihood, the response of mononuclear cells to secondary ultrafiltrate in culture involved a subset of CD4+ T cells other than those of the primary ultrafiltrate. Conclusions: Free endosomal epitopes, released from the maternal-fetal interface and necrotic areas of diseased liver, inducing expansion of regulatory T cells, provided a type of endogenous, autonomic immunotherapy. The post-partum flare-up of the disease could be due to the sudden interruption of endogenous immunotherapy at delivery and to the inflammatory response to microcomplexes that are recognized by autoreactive T cells.
doi:10.1186/s41231-018-0022-3 fatcat:l2ckehk3j5cn3e3ckux2pizk6y