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Hormonal imbalance may be an important factor in the severity of multiple sclerosis (MS) disease. In this context, hormone therapy has been shown to have immunoregulatory potential in various experimental approaches. There is increasing evidence of potentially beneficial effects of thyroid, melatonin, and sex hormones in MS models. These hormones may ameliorate the neurological impairment through immunoregulatory and neuroprotective effects, as well as by reducing oxidative stress. Expanding our knowledge of hormone therapy may be an effective step toward identifying additional molecular/cellular pathways in MS disease. In this review, we discuss the role of several important hormones in MS pathogenesis in terms of their effects on immunoregulatory aspects and neuroprotection.

Progressive multifocal leukoencephalopathy (PML) is an opportunistic viral disease of the brain—caused by human polyomavirus 2. It affects patients whose immune system is compromised by a corresponding underlying disease or by drugs. Patients with an underlying lymphoproliferative disease have the worst prognosis with a mortality rate of up to 90%. Several therapeutic strategies have been proposed but failed to show any benefit so far. Therefore, the primary therapeutic strategy aims to reconstitute the impaired immune system to generate an effective endogenous antiviral response. Recently, anti-PD-1 antibodies and application of allogeneic virus-specific T cells demonstrated promising effects on the outcome in individual PML patients. This article aims to provide a detailed overview of the literature with a focus on these two treatment approaches. Supplementary Information The online version contains supplementary material available at 10.1007/s00415-021-10952-5.

Objective The interplay between systemic inflammation, activity of lymphoid organs and lymphoma activity in CD19-targeting chimeric antigen receptor (CAR)-T-cell immunotherapy, and its significance for response and toxicity, is not well defined. Methods Using serial 18F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT), metabolic parameters of lymphoma and lymphoid organs were analyzed in ten patients receiving Tisagenlecleucel (an autologous CD19 CAR-T cell product) for relapsed or refractory diffuse large B-cell lymphoma. The prevalence and severity of toxicity (e.g., neurotoxicity) were noted. Results Achieving remission required early metabolic response (P = 0.0476). Early suppression of metabolic activity of lymphoid organs (spleen, P = 0.0368; lymph nodes, P = 0.0470) was associated with poor outcome. Lymphoma metabolic activity was significantly higher in patients with neurotoxicity (P = 0.0489). Conclusions Early metabolic changes in lymphoma lesions and off-target lymphoid organs parallel medium-term response to CAR-T-cell therapy. PET can identify patients at risk for severe toxicity.