Levels Of Pathogenic Autoantibodies Research Articles

Generate-Boost: study protocol for a prospective, multicenter, randomized controlled, double-blinded phase II trial to evaluate efficacy and safety of bortezomib in patients with severe autoimmune encephalitis

BackgroundAutoimmune encephalitis is a new spectrum of autoimmune disorders of the central nervous system (CNS), which are characterized by pathogenic autoantibodies against neuronal surface antigens. Clinical presentations range from acute to subacute encephalopathy with neurological and psychiatric symptoms, and life-threatening autonomic dysfunction in severe cases. There exist no approved therapies nor is data available from controlled clinical trials. Patients are usually treated with diverse combinations of immunotherapy. However, effect of immunotherapy on antibody-producing cells and thus on levels of pathogenic autoantibodies is insufficient. Therefore, therapeutic response is sometimes prolonged with necessity of long-time intensive care treatment and also irreversible deficits occur in severe cases. This trial will investigate the efficacy and safety of bortezomib, a proteasome inhibitor known to selectively deplete plasma cells, in patients with severe autoimmune encephalitis who have been treated with rituximab with insufficient response.MethodsGenerate-Boost is an investigator-initiated, multicenter, double-blinded, randomized controlled phase II trial which will be conducted in specialized neurological hospitals within the GENERATE (GErman NEtwork for Research on AuToimmune Encephalitis) network in Germany. Adult patients with severe autoimmune encephalitis (modified Rankin scale, mRS ≥ 3), autoantibodies against neuronal surface antigens, and pretreatment with rituximab are eligible for study participation. Fifty patients will be randomized 1:1 and undergo up to 3 cycles (each 21 days with 4 s. c. applications) of bortezomib or placebo. All patients will receive concomitant medication with dexamethasone, acyclovir and co-trimoxazole. The primary efficacy endpoint is the mRS score 17 weeks after first treatment application. Secondary endpoints are neurocognitive function, antibody titers, markers of neuronal cell damage, length of ICU/hospital stay, and mRS and Glasgow coma scale scores throughout the trial up to week 17. General and bortezomib-specific adverse events are monitored continuously.DiscussionThe expected outcome of the study is to obtain first reliable data on a hypothesis-driven therapeutic option in severe and difficult-to-treat autoimmune encephalitis. If treatment with bortezomib is beneficial in these cases, this will be the basis for implementation in the current guidelines.Trial registrationClinicaltrials.gov, NCT03993262. Registered June 20, 2019;German Clinical Trials Register, DRKS00017497.

Intravenous immunoglobulin G in the treatment of autoimmune bullous disease.

Intravenous immunoglobulin G in the treatment of autoimmune bullous disease.

7th International Immunoglobulin Conference: Immunomodulation.

Rheumatoid arthritis (RA) is a debilitating autoimmune disease that is usually treated aggressively to slow the rate of joint destruction. The therapeutic strategy used at the French centre, described here, is to use the non-biological disease-modifying drug, methotrexate, as first-line therapy and to add biological agents as second-line treatment. The two other autoimmune diseases discussed in this session were immunobullous skin diseases, and secondary recurrent miscarriage (RM). In the former conditions, low levels of pathogenic autoantibodies can be achieved with adjuvant intravenous immunoglobulin (IVIg) therapy, usually in combination with an immunosuppressant. Secondary RM has an autoimmune basis, as shown by high tumour necrosis factor (TNF)-α levels and specific human leucocyte antigen (HLA) polymorphisms. Although the mechanism is not yet known, IVIg may also be an effective treatment, despite the generally low doses used in published studies.

Successful treatment of autoimmune thrombocytopenic purpura with rituximab in a dialysis patient with systemic lupus erythematosus

Autoimmune thrombocytopenic purpura (ATP) in systemic lupus erythematosus involves autoantibody mediated destruction of platelets. In dialysis patients with refractory ATP which is unresponsive to corticosteroid and immunosuppressive agents, the management is difficult. B cell targeted therapy with rituximab has emerged as a promising agent by reducing the levels of pathogenic autoantibodies. However, its safety and efficacy in dialysis patients are uncertain. In this report, we described a dialysis patient with refractory lupus-related ATP, whose platelet counts responded only to rituximab. Furthermore, no severe side effects were noted during the treatment period, suggesting that rituximab can be administered safely in dialysis patients.