Open ADAMTS13 conformation in immune-mediated thrombotic thrombocytopenic purpura is induced by anti- ADAMTS13 autoantibodies and corresponds with an ongoing ADAMTS13 pathology

status: accepte

Hydroxychloroquine reverses the prothrombotic state in a mouse model of antiphospholipid syndrome: Role of reduced inflammation and endothelial dysfunction

International audienceAntiphospholipid antibodies (aPL) promote endothelial dysfunction, inflammation and pro-coagulant state. We investigated the effect of hydroxychloroquine (HCQ) on prothrombotic state and endothelial function in mice and in human aortic endothelial cells (HAEC). Human aPL were injected to C57BL/6 mice treated or not with HCQ. Vascular endothelial function and eNOS were assessed in isolated mesenteric arteries. Thrombosis was assessed both in vitro by measuring thrombin generation time (TGT) and tissue factor (TF) expression and in vivo by the measurement of the time to occlusion in carotid and the total thrombosis area in mesenteric arteries. TGT, TF, and VCAM1 expression were evaluated in HAEC. aPL increased VCAM-1 expression and reduced endothelium dependent relaxation to acetylcho-line. In parallel, aPL shortened the time to occlusion and extended thrombus area in mice. This was associated with an overexpression of TF and an increased TGT in mice and in HAEC. HCQ reduced clot formation as well as TGT, and improved endothelial-dependent relaxations. Finally, HCQ increased the p-eNOS/eNOS ratio. This study provides new evidence that HCQ improves procoagulant status and vascular function in APS by modulating eNOS, leading to an improvement in the production of NO

Assessment of the efficacy and safety of tocilizumab in patients over 80 years old with giant cell arteritis

International audienceObjective: To assess the efficacy and tolerance of tocilizumab (TCZ) in giant cell arteritis (GCA) patients over 80.Method: GCA patients over 80 years old from the French Study Group for Large Vessel Vasculitis register who received TCZ were analyzed.Results: Twenty-one GCA patients (median age 84 [81-90] years old, including nine over 85) received TCZ for the following nonexclusive reasons: glucocorticoid (GC)-sparing effect in 14, relapsing disease in 8, disease severity in 4, and/or failure of another immunosuppressant in 4. TCZ was introduced with GCs at diagnosis in 6 patients and at 8 [3-37] months after GC initiation in 15 others. After a median delay of 8 [2-21] months post-TCZ introduction, 14 (67%) patients were able to definitively stop GCs, including 6 who were GC-dependent before TCZ. At the last follow-up (median 20 [3-48] months), 11 (52%) patients had definitively stopped TCZ, and 2 additional patients had stopped but relapsed and resumed TCZ. Seven (33%) patients experienced 11 adverse events: hypercholesterolemia in 4 patients; infections, i.e., pyelonephritis, bronchitis, and fatal septic shock associated with mesenteric infarction following planned surgery (GCs were stopped for 1 year and TCZ infusions for 2 months), respectively, in 3 patients; moderate thrombocytopenia and moderate neutropenia in 2 patients; and a 5-fold increase in transaminase levels in another that improved after TCZ dose reduction.Conclusion: TCZ remains a valuable GC-sparing option in the oldest GCA patients with an interesting risk-benefit ratio. Mild-to-moderate adverse events were observed in one-third of patients

Patient anti-ADAMTS13 autoantibodies induce an open ADAMTS13 conformation in immune-mediated thrombotic thrombocytopenic purpura

status: accepte

Open ADAMTS13 conformation in immune-mediated thrombotic thrombocytopenic purpura is induced by anti-ADAMTS13 autoantibodies and corresponds with an ongoing ADAMTS13 pathology

status: accepte

Open ADAMTS13 conformation in immune-mediated thrombotic thrombocytopenic purpura is induced by anti-ADAMTS13 autoantibodies and corresponds with an ongoing ADAMTS13 pathology

status: accepte

Open ADAMTS13 Conformation in Immune-Mediated Thrombotic Thrombocytopenic Purpura Is Induced By Anti-ADAMTS13 Autoantibodies and Corresponds with an Ongoing ADAMTS13 Pathology

60th Annual Meeting of the American-Society-of-Hematology (ASH), San Diego, CA, DEC 01-04, 201

Severe enterovirus infections in patients with immune-mediated inflammatory diseases receiving anti-CD20 monoclonal antibodies

International audienceObjective Patients with X linked agammaglobulinemia are susceptible to enterovirus (EV) infections. Similarly, severe EV infections have been described in patients with impaired B-cell response following treatment with anti-CD20 monoclonal antibodies (mAbs), mostly in those treated for haematological malignancies. We aimed to describe severe EV infections in patients receiving anti-CD20 mAbs for immune-mediated inflammatory diseases (IMIDs). Methods Patients were included following a screening of data collected through the routine surveillance of EV infections coordinated by the National Reference Center and a review of the literature. Additionally, neutralising antibodies were assessed in a patient with chronic EV-A71 meningoencephalitis. Results Nine original and 17 previously published cases were retrieved. Meningoencephalitis (n=21/26, 81%) associated with EV-positive cerebrospinal fluid (n=20/22, 91%) was the most common manifestation. The mortality rate was high (27%). EV was the only causal agents in all reported cases. Patients received multiple anti-CD20 mAbs infusions (median 8 (5–10)), resulting in complete B-cell depletion and moderate hypogammaglobulinemia (median 4.9 g/L (4.3–6.7)), and had limited concomitant immunosuppressive treatments. Finally, in a patient with EV-A71 meningoencephalitis, a lack of B-cell response to EV was shown. Conclusion EV infection should be evoked in patients with IMIDs presenting with atypical organ involvement, especially meningoencephalitis. Anti-CD20 mAbs may lead to impaired B-cell response against EV, although an underlying primary immunodeficiency should systematically be discussed