BackgroundAccumulating evidence has shown that the inflammatory process participates in the pathogenesis of amyotrophic lateral sclerosis (ALS), suggesting a therapeutic potential of anti-inflammatory agents. Janus kinase 2 (JAK2), one of the key molecules in inflammation, transduces signals downstream of various inflammatory cytokines, and some Janus kinase inhibitors have already been clinically applied to the treatment of inflammatory diseases. However, the efficacy of JAK2 inhibitors in treatment of ALS remains to be demonstrated. In this study, we examined the role of JAK2 in ALS by administering a selective JAK2 inhibitor, R723, to an animal model of ALS (mSOD1G93A mice).FindingsOrally administered R723 had sufficient access to spinal cord tissue of mSOD1G93A mice and significantly reduced the number of Ly6c positive blood monocytes, as well as the expression levels of IFN-γ and nitric oxide synthase 2, inducible (iNOS) in the spinal cord tissue. R723 treatment did not alter the expression levels of Il-1β, Il-6, TNF, and NADPH oxidase 2 (NOX2), and suppressed the expression of Retnla, which is one of the markers of neuroprotective M2 microglia. As a result, R723 did not alter disease progression or survival of mSOD1G93A mice.ConclusionsJAK2 inhibitor was not effective against ALS symptoms in mSOD1G93A mice, irrespective of suppression in several inflammatory molecules. Simultaneous suppression of anti-inflammatory microglia with a failure to inhibit critical other inflammatory molecules might explain this result.Electronic supplementary materialThe online version of this article (doi:10.1186/s12974-014-0179-2) contains supplementary material, which is available to authorized users.

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Exacerbation of rheumatic disease after vaccination against SARS-CoV-2 is being reported. However, there are only a few cases of new-onset rheumatic diseases. We present two cases of new-onset persistent polyarthritis that developed in patients after receiving the mRNA vaccine against SARS-CoV-2. One patient had bilateral pleural effusions with markedly elevated serum interferon (IFN)-β, while the other had no effusion, with serum IFN-β comparable with that in healthy subjects. Other cytokines were unaltered in association with effusion. Both patients responded well to treatment with 20 mg prednisolone. Although more investigations are needed, the marked increase in serum IFN-β levels observed in the case with pleural effusion may reflect an excessive response from the innate immune system to mRNA vaccines.

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Patients with autoimmune vasculitis present with diverse organ-threatening symptoms, but the underlying immunological basis of the clinical heterogeneity remains poorly understood. We conducted single-cell transcriptome and surface proteome analyses using CITE-seq on 109,350 peripheral blood mononuclear cells (PBMCs) and CyTOF on 737,794 PBMCs from newly-onset patients with microscopic polyangiitis (MPA) and age-matched healthy donors. Increased proportions of activated CD14+ monocytes, CD14+ monocytes expressing interferon signature genes (ISGs), cytotoxic CD8+ T cells, and killer immunoglobulin-like receptor (KIR)+ CD8+ T cells were distinctive features of MPA. Patient-specific analysis classified MPA into two groups characterized by CD14+ monocyte signature gene expression (MPA-MONO) and ISG expression (MPA-IFN). The MPA-MONO group was characterized by a high proportion of activated CD14+ monocytes, which persisted before and after immunosuppressive therapy. Patients in this group had a high rate of relapse and were clinically defined by increased monocyte ratio in the total PBMC count and high C-reactive protein titers. The MPA-IFN group was characterized by a high proportion of ISG+ CD14+ monocytes, which significantly decreased following treatment. Patients in this group showed good response to immunosuppressive therapy and were clinically defined by high serum interferon-alpha concentrations, renal symptoms, and high myeloperoxidase-antineutrophil cytoplasmic antibody (MPO-ANCA) titers. Our findings identify the immunological phenotypes of MPA and provide clinical recommendations for personalized treatment based on accurate prognostic prediction.