Dermatomyositis is a rare, type I interferon-driven autoimmune disease, which can affect muscle, skin and internal organs (especially the pulmonary system). In 2021, we have noted an increase in new-onset dermatomyositis compared to the years before the SARS-CoV-2 pandemic in our center. We present four cases of new-onset NXP2 and/or MDA5 positive dermatomyositis shortly after SARS-CoV-2 infection or vaccination. Three cases occurred within days after vaccination with Comirnaty and one case after SARS-CoV-2 infection. All patients required intensive immunosuppressive treatment. MDA5 antibodies could be detected in three patients and NXP2 antibodies were found in two patients (one patient was positive for both antibodies). In this case-based systematic review, we further analyze and discuss the literature on SARS-CoV-2 and associated dermatomyositis. In the literature, sixteen reports (with a total of seventeen patients) of new-onset dermatomyositis in association with a SARS-CoV-2 infection or vaccination were identified. Ten cases occurred after infection and seven after vaccination. All vaccination-associated cases were seen in mRNA vaccines. The reported antibodies included for instance MDA5, NXP2, Mi-2 and TIF1γ. The reviewed literature and our cases suggest that SARS-CoV-2 infection and vaccination may be considered as a potential trigger of interferon-pathway. Consequently, this might serve as a stimulus for the production of dermatomyositis-specific autoantibodies like MDA5 and NXP2 which are closely related to viral defense or viral RNA interaction supporting the concept of infection and vaccination associated dermatomyositis.
Background The plasticity of T helper-17 (Th17) and regulatory T (Treg) cells may be a clue to pathogenesis of Juvenile Idiopathic Arthritis (JIA). It is still unclear, whether targeted suppression of Interleukin (IL)-17 is able to influence regulatory function of Treg to control pro-inflammatory effectors in JIA. This study aimed to assess the effect of a Th17-stimulating cytokine environment and of IL-17A-inhibition on phenotype plasticity and suppressive function of Treg derived from JIA patients. Methods Th17 and Treg characteristics of CD4+ helper T cells were investigated in blood samples of JIA patients with oligo- and polyarticular pattern and healthy controls (HC). Isolated CD4+CD25+CD127− cells defined as Treg were cultivated with Th17-inducing cytokine environment as well as with IL-17A-inhibitors and analyzed for plasticity of phenotype by flow cytometry. Furthermore, inhibitory function of Treg on autologous effectors after cultivation with these stimuli was determined by suppression assays. Results Our findings demonstrated significantly elevated proportions of Th17 and Th17-like Treg in JIA compared to HC. After incubation with Th17-inducing stimuli, increased FoxP3 expression in separated Treg in JIA and an impaired suppressive capacity in JIA and HC were found. Blockade of IL-17A resulted in adjustment of FoxP3-expression in JIA to proportions found in controls and in regular suppressive function. Conclusions Our results demonstrate an induction of FoxP3 expressing Treg by Th17-inducing cytokines with concomitant mitigated suppressive function. In contrast, specific IL-17A blockade maintains suppressive Treg function and adjusted FoxP3-expression in JIA to levels found in controls. These findings may help to provide experimental evidence for the successful clinical use of IL-17A inhibition in JIA patients.
Zusammenfassung Hintergrund Therapierefraktäre Arthritiden sind ein häufiges Problem im rheumatologischen Alltag und können eine differentialdiagnostische Herausforderung darstellen. Chronische Infektionen durch Tropheryma whipplei (T. whipplei) sollten in diesen Fällen bedacht werden. Ziel der Arbeit Anhand von 5 klinischen Fällen werden in dieser fallbasierten Übersichtsarbeit die diagnostischen und therapeutischen Prinzipien im Management der chronischen T.-whipplei-Infektion erläutert. Ergebnis Der Morbus Whipple ist eine infektiöse Multisystemerkrankung, die durch das Bakterium T. whipplei ausgelöst wird. Typischerweise manifestiert sich die Erkrankung mit Arthralgien, Gewichtsverlust und Diarrhoen. Die Gelenkmanifestationen gehen den gastrointestinalen Krankheitserscheinungen häufig mehrere Jahre voraus. Neben systemischen Manifestationen (Morbus Whipple) kann T. whipplei auch zu lokalisierten Infektionen der Gelenke ohne gastrointestinale Beteiligung führen. Die Gelenkmanifestationen systemischer und lokalisierter T.-whipplei-Infektionen werden fälschlicherweise häufig als Zeichen verschiedener autoimmunologischer Arthritiden gedeutet. Diskussion Bei der Abklärung therapierefraktärer Arthritiden sollte an einen Morbus Whipple und lokalisierte Gelenkinfektionen durch T. whipplei gedacht werden. Diagnostisch wegweisend ist die Untersuchung des Gelenkpunktates auf T. whipplei mittels Polymerasekettenreaktion.
Immune-mediated thrombotic thrombocytopenic purpura (iTTP) is a potentially fatal acquired thrombotic microangiopathy syndrome that frequently develops in the context of infectious diseases or systemic autoimmune conditions including connective tissue diseases. We report the case of a 42-year-old female suffering from severe iTTP associated with anti-Jo-1 positive antisynthetase syndrome, which was successfully treated with combination therapy of intravenous immune globulin, rituximab and plasma exchange. Based on a systematic review of the literature, two additional cases of idiopathic inflammatory myopathy-associated iTTP (secondary iTTP) were identified. In conclusion, iTTP may be a rare complication of IIM that clinicians should consider in cases of marked thrombocytopenia. Further work-up of this finding should include a peripheral blood smear (schistocyte count) and ADAMTS13 activity. The concomitant manifestation of these autoimmune conditions may require intensive immunosuppressive therapy.
BackgroundKu-antibodies are one of the myositis-associated antibodies linked with muscle involvement in many connective tissue diseases. The histopathological pattern of Ku+myositis is described diversely with inflammatory and necrotic aspects, however, a detailed morphological characterization of Ku+myositis is still missing.ObjectivesThe aim of the study was to analyze histopathological and transcriptional aspects of patients with Ku+myositis to gain new insights in possible pathophysiological mechanisms.Methods23 biopsy samples from patients with clinical and morphological signs of myositis and positive Ku-antibodies were studied by histopathology, immunohistochemistry, and quantitative polymerase chain reaction (qPCR) and compared with biopsies derived from non-disease controls (NDCs) and immune-mediated necrotizing myopathy (IMNM) at the Department of Neuropathology of Charité university hospital Berlin.ResultsMean patient’s age was 55 years, 91% were women and the most common rheumatological diagnosis was overlap with systemic sclerosis (30%), followed by isolated myositis (26%) and overlap with primary sjögren’s syndrome or rheumatoid arthritis (13% respectively). Creatine kinase elevation was present in 91% of the patients. Histopathologically, we noticed a broad phenotype spectrum with mild to severe myositis with predominantly MHC class I overexpression and milder MHC class II overexpression. 87% of the biopsies showed necrosis combined with inflammatory aspects of variable degree. Infiltrates were mainly CD68+cells (average of 213 cells per 10 high power fields (HPF)), followed by CD3+cells (76 cells/10 HPF), whereas CD20+or CD138+cells were rare (8 respectively 14 cells/10 HPF). Furthermore, we detected small vacuoles in 59% and large areas of p62+aggregates in 62% of the biopsies. Similarly, aggregates of LC3 and myotilin were found in 60% and 76% respectively. Immunofluorescence staining showed co-localization of p62 and myotilin indicating protein aggregates and induction of autophagy pathways.P62gene expression was neither elevated in Ku+patients nor in IMNM patients compared to NDC (Figure 1A).SIGLEC1gene expression was significantly elevated in Ku+patients compared to IMNM patients and NDC (Figure 1B).ConclusionIn this study, we defined a histopathological pattern of Ku+myositis with predominant MHC class I expression, necrosis, small vacuoles and inflammation as well as peculiar p62+and LC3+aggregation in severely inflammatory biopsy samples. Whilst there definitely is a broad spectrum of presentation, MHC class I expression, necrosis and p62/LC3+aggregates seem to be the defining aspects of the histopathological presentation.Figure 1.Transcriptional analysis ofLC3,P62andSIGLEC1Quantitative polymerase chain reaction was used to analyze the gene expression ofLC3,P62andSIGLEC1. Violin plots display fold-change versus non disease controls (NDC), calculated by [2^-(ΔCT Ku+patients/immune-mediated necrotizing myositis (IMNM) -ΔCT NDC)].ALC3gene levels are elevated in Ku+patients compared to IMNM (p=0.0015), whilstP62levels do not differ from NDC.BSIGLEC1gene expression is significantly elevated in Ku+patients compared to IMNM patients (p=0.0026) and NDC (p<0.0001).AcknowledgementsMTH received a project scholarship by the Arbeitsgemeinschaft Junge Rheumatologie Deutschland (AGJR) (Working Group Young Rheumatology from the German Society for Rheumatology).MK, CP and WS share last authorship.Disclosure of InterestsMarie-Therese Holzer: None declared, Udo Schneider: None declared, Anne Schänzer: None declared, Sarah Léonard-Louis: None declared, Olivier Benveniste: None declared, Joachim Weis: None declared, Kristl G Claeys Grant/research support from: KGC is Chairholder of the Emil von Behring Chair for Neuromuscular and Neurodegenerative Disorders by CSL Behring, Benedikt Schoser: None declared, Frederica Montagnese Speakers bureau: Lupin/Hormosan, Sanofi, RG-Gesellschaft, DYNE, Consultant of: Lupin/Hormosan, Sanofi, RG-Gesellschaft, DYNE, Akinori Uruha: None declared, Melanie Huber: None declared, Laure Gallay: None declared, Nathalie Streichenberger: None declared, Martin Krusche: None declared, Corinna Preuße Speakers bureau: Alexion, Werner Stenzel: None declared.
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