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Background: Our previous results showed that intrasynovial Rifamycin SV caused the lysis of synoviocites and freed the autoantigens which in turn stimulated the immunoregulatory rather than autoreactive T cell response in rheumatoid patients. Here, we hypothesize that disruption in vitro of peripheral blood mononuclear cells, by freeze/thawing or by lytic action of Rifamycin SV, would induce the release of endosomal pathogenic autoantigens from APCs present in the circulation, which could then be isolated from degrading enzymes by ultrafiltration.Methods: The preparation of the ultrafiltrates are based on the rupture of PBMCs (5 × 10(6) cells/mL) by the addition of Rifamycin SV in culture (250 μg/mL), which causes the lysis of 90 % of the cells in 3 h, or by three cycles of freeze/thawing of the PBMC, from -80 °C to room temperature. The lysate and the fragmented cells were then centrifuged and ultrafiltered by passage through a filtration device with a cut-off of 10 kDa. Also the synovial fluid was subjected to ultrafiltration.Results and Conclusions: At clinical monitoring of the 30th day, 22/58 (38 %) patients subcutaneously treated with the autologous ultrafiltrate prepared by the freeze/thawing of PBMCs reached an ACR20. Comparable results were obtained with the other two ultrafiltrates. Cell cultures The addition of ultrafiltrates to rheumatoid PBMCs cultures led to the upregulation of a marker for T-regulatory cells, and downregulation of a cell proliferation marker; changes that together have the meaning of a global immunomodulatory response and that only a specific antigen (ultrafiltrate UF-f/t) might induce in the rheumatoid patient, probably by activating pre-existing protective network. Experimental arthritis All the ultrafiltrates except that prepared by Rifamycin SV were able to modulate the adjuvant arthritis in rats. In particular, longlasting synovial fluid induced a significant reduction of the severity of subsequent arthritis (p < 0.01) while SF from recent RA effusion (5-10 days after a previous complete extraction) and knee osteoarthrosis were ineffective. It is reasonable to assume there are at least two unknown endosomal immunoactive epitopes; one developing its immunotherapeutic property in RA, and the other, related to the molecule of HSP60, reduces the severity of oncoming arthritis. Both epitopes are present in humans, have a molecular weight of ≤10 kDa and do not appear to be bystander antigens. Please see Additional file 1 for the abstract in Italian. [ABSTRACT FROM AUTHOR]

Background: Abatacept (ABA) is a fusion receptor protein containing the CTLA-4 domain that prevents the activation of naïve T cells by binding the CD80 and CD86 molecules expressed on the surface of dendritic cells, indicated for the treatment of moderate to severe rheumatoid arthritis (RA). There is still little evidence concerning the safety of ABA in RA patients with positive serology for hepatitis virus B (HBV) infection. Case Presentation: We report the case of a HBV infection reactivation in an ABA-treated male RA patient. The patient (caucasian race, 66-year-old) was diagnosed with RA in Novembre 2010 and in December 2010 he started a treatment with prednisone plus subcutaneous methotrexate. In October 2011, an anti-TNF agent (golimumab) was added but soon discontinued due to an adverse event. At baseline, screening for HBV markers showed a positivity for HBcAb and HBeAb IgG, being HBsAg, HBsAb, HBcAb IgM, HBeAg and HBV DNA negative. Serum amino-transferase (AST and ALT) levels were within the normal range. In January 2012 he was swapped to intravenous treatment with ABA 750 mg/month, that allowed the achievement of a good clinical response and the permanent discontinuation of corticosteroids. In November 2013, laboratory reports showed that he was positive for HBcAb but negative for the remaining HBV markers, and had a slightly increased AST level and, in December 2013, he became HBV DNA positive (326 IU/mL). In January 2014, his HBV DNA levels had further increased and ABA was stopped while maintaining MTX. He started lamivudine 100 mg/day in January 2014. After 1 month of lamivudine, his HBV DNA levels became undetectable (<10 IU/mL) and liver function was normal although RA had been reactivated (DAS28 5.53). Treatment with ABA was therefore resumed with the achievement of a good response after 6 months. The patient is currently being treated with lamivudine 100 mg/day, i.v. ABA 750 mg/month, and MTX 15 mg/week, with a good response (DAS28 2.27 in October 2015), and constantly monitored without any further evidence of HBV infection reactivation. Conclusions: Although there are still few reports in literature, we suggest caution in HBV- occult carriers RA patients undergoing a treatment with abatacept. [ABSTRACT FROM AUTHOR]