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Objective To evaluate the main outcomes of disease activity and their association with other measures of activity, damage, and quality of life in patients with idiopathic inflammatory myopathy (IIM) according to time since diagnosis and positivity to antisynthetase autoantibodies (ASAs). Methods Cross-sectional multicenter study within the Spanish Myo-Spain registry. Cases were classified as incident (≤ 12 months since diagnosis) and prevalent. The main outcomes of disease activity were the Myositis Disease Activity Assessment visual analogue scale (MYOACT), the Manual Muscle Test 8 (MMT-8), physician global activity (PhGA), and extramuscular activity. Other measures of activity, damage, and quality of life included patient global disease activity, MYOACT muscular, creatine phosphokinase, Health Assessment Questionnaire, physician and patient global damage, global damage of the Myositis Damage Index, and the 12-item Short-Form Health Survey (SF-12). We analyzed associations using a multivariate generalized linear model and a simple linear regression model. Results A total of 554 patients with different diagnostic subgroups of IIM were included (136 incident and 418 prevalent cases), with 215 ASA-positive patients (58 incident and 157 prevalent cases). All measures of disease activity were higher in the incident cases ( p  < 0.05), except for MYOACT muscular and creatine phosphokinase, for which no differences were recorded in ASA-positive patients. No differences were found between incident and prevalent cases for measures of damage. Values for the physical component of the SF-12 were higher in the prevalent cases ( p  < 0.05). The multivariate model was initially significant overall for the main activity outcomes. Positivity to ASAs was positively and negatively associated with the MYOACT index and MMT-8, respectively ( p  < 0.05), although no association was recorded with PhGA and extramuscular activity. Prevalent cases were negatively associated with the main outcomes of activity, except with MMT-8, for which the association was positive ( p  < 0.05). Conclusions The main activity outcomes validated in polymyositis and dermatomyositis could also be used in other subtypes of IIM, such as antisynthetase syndrome. Recent diagnosis is associated with greater disease activity, as assessed based on these activity outcomes. PhGA and extramuscular activity are not modified by ASA positivity, thus supporting their preferred use for assessing treatment response in IIM with ASAs.

To describe the characteristics of systemic juvenile idiopathic arthritis (sJIA) and adult-onset Still’s disease (AOSD), compare their presentation and evolution, and analyse possible complication predictors. Multicenter study. Data were retrieved from a hospital-based study of patients with a diagnosis or suspected diagnosis of sJIA or AOSD according to the responsible physician and followed-up for at least one year. Descriptive variables (classification criteria, clinical manifestations, complications, family, and personal history) were collected at disease onset and during follow-up. We present the clinical characteristics of 326 patients, 67% of whom had a diagnosis of sJIA and 33% of AOSD. Clinical manifestation frequencies were similar between the two groups, except for odynophagia, which was significantly more frequent in AOSD than in sJIA (78.4% vs. 25.5%; p < 0.0001). Among the complications, macrophage activation syndrome (MAS) was significantly more common in sJIA than in AOSD (24.4% vs. 9.5%; p = 0.002), to the extent that an sJIA diagnosis significantly increased the risk of MAS, together with serositis presence, and the need for biological therapy. Patients with sJIA and AOSD showed similar characteristics, supporting the idea that they are both part of Still’s disease, but are expressed at different ages. Differences in manifestations and complications might be due to different management between diseases and immune response maturity.

Immunotherapy has raised high expectations in the treatment of virtually every cancer. Many current efforts are focused on ensuring the efficient delivery of active cytotoxic cells to tumors. It is assumed that, once these active cytotoxic cells are correctly engaged to cancer cells, they will unfailingly eliminate the latter, provided that inhibitory factors are in check. T cell bispecific antibodies (TCBs) and chimeric antigen receptors (CARs) offer an opportunity to test this assumption. Using TCB and CARs directed against HER2, here we show that disruption of interferon-gamma signaling confers resistance to killing by active T lymphocytes. The kinase JAK2, which transduces the signal initiated by interferon-gamma, is a component repeatedly disrupted in several independently generated resistant models. Our results unveil a seemingly widespread strategy used by cancer cells to resist clearance by redirected lymphocytes. In addition, they open the possibility that long-term inhibition of interferon-gamma signaling may impair the elimination phase of immunoediting and, thus, promote tumor progression. Several mechanisms of resistance to T cell-engaging therapies have been described for solid tumors. Here, by using T cell bispecific antibodies and chimeric antigen receptors (CAR) T cells targeting HER2, the authors show that cancer cell intrinsic disruption of interferon-gamma signalling, including downregulation of JAK2, confers resistance to T-cell mediated cytotoxicity.