CD19-Targeting CAR T Cells for Myositis and Interstitial Lung Disease Associated With Antisynthetase Syndrome.

Importance: Autoimmune disorders can affect various organs and if refractory, can be life threatening. Recently, CD19-targeting-chimeric antigen receptor (CAR) T cells were efficacious as an immune suppressive agent in 6 patients with refractory systemic lupus erythematosus and in 1 patient with antisynthetase syndrome. Objective: To test the safety and efficacy of CD19-targeting CAR T cells in a patient with severe antisynthetase syndrome, a complex autoimmune disorder with evidence for B- and T-cell involvement. Design, Setting, and Participants: This case report describes a patient with antisynthetase syndrome with progressive myositis and interstitial lung disease refractory to available therapies (including rituximab and azathioprine), who was treated with CD19-targeting CAR T cells in June 2022 at University Hospital Tübingen in Tübingen, Germany, with the last follow-up in February 2023. Mycophenolate mofetil was added to the treatment to cotarget CD8+ T cells, hypothesized to contribute to disease activity. Exposure: Prior to treatment with CD19-targeting CAR T cells, the patient received conditioning therapy with fludarabine (25 mg/m2 [5 days before until 3 days before]) and cyclophosphamide (1000 mg/m2 [3 days before]) followed by infusion of CAR T cells (1.23×106/kg [manufactured by transduction of autologous T cells with a CD19 lentiviral vector and amplification in the CliniMACS Prodigy system]) and mycophenolate mofetil (2 g/d) 35 days after CD19-targeting CAR T-cell infusion. Main Outcomes and Measures: The patient's response to therapy was followed by magnetic resonance imaging of the thigh muscle, Physician Global Assessment, functional muscle and pulmonary tests, and peripheral blood quantification of anti-Jo-1 antibody levels, lymphocyte subsets, immunoglobulins, and serological muscle enzymes. Results: Rapid clinical improvement was observed after CD19-targeting CAR T-cell infusion. Eight months after treatment, the patient's scores on the Physician Global Assessment and muscle and pulmonary function tests improved, and there were no detectable signs of myositis on magnetic resonance imaging. Serological muscle enzymes (alanine aminotransferase, aspartate aminotransferase, creatinine kinase, and lactate dehydrogenase), CD8+ T-cell subsets, and inflammatory cytokine secretion in the peripheral blood mononuclear cells (interferon gamma, interleukin 1 [IL-1], IL-6, and IL-13) were all normalized. Further, there was a reduction in anti-Jo-1 antibody levels and a partial recovery of IgA (to 67% of normal value), IgG (to 87%), and IgM (to 58%). Conclusions and Relevance: CD19-targeting CAR T cells directed against B cells and plasmablasts deeply reset B-cell immunity. Together with mycophenolate mofetil, CD19-targeting CAR T cells may break pathologic B-cell, as well as T-cell responses, inducing remission in refractory antisynthetase syndrome.

Nonthermal effects of lifelong high-frequency electromagnetic field exposure on social memory performance in rats.

We are today surrounded almost constantly by high-frequency electromagnetic fields (EMFs) from mobile communications base stations. To date, however, there has been little concern regarding nonthermal effects of EMFs on cognition. In the present study, male and female rats were subjected to continuous far-field exposure to a frequency of 900-MHz (Global System for Mobile Communications [GSM]) or 1.966-GHz (Universal Mobile Telecommunications System [UMTS]) at 0.4 W/kg. Memory performance of adult EMF-exposed and sham-exposed female rats (at 6 months of age) and male rats (at 3 and 6 months of age) was tested using a social discrimination procedure. For this procedure, a target juvenile male was introduced to the subject's home cage for 4 min (Trial 1). After 30 min, the same target animal and a novel juvenile male were simultaneously presented to the subject for 4 min (Trial 2). Differences in sniffing duration to the familiar and novel target rats during Trial 2 were used to assess memory performance. EMF-exposed females exhibited no differences in sniffing duration compared with controls. In contrast, the sniffing durations of EMF-exposed males at 3 months of age were significantly affected. At 6 months of age, GSM-, but not UMTS-, exposed male adults showed a memory performance deficit. These findings provide new insight into the nonthermal effects of long-term high-frequency EMF exposure on memory.