Adult onset Still's disease (AOSD) is a rare inflammatory disorder that remains poorly understood. Its pathophysiology is yet to be completely elucidated, but is known to consist mainly on a cytokine ...cascade, responsible for the systemic manifestations. AOSD diagnosis is usually difficult and delayed, with physicians having to rule out several other conditions, including cancer or infectious diseases. Prognosis is heterogeneous and difficult to establish, ranging from benign outcome to chronic destructive polyarthritis and/or life-threatening events. In addition, treatment remains to be codified, especially considering the development of new drugs. In this commentary, we attempt to elucidate the complexity of AOSD and to highlight the need of working on prognostic tools for this disorder. We also discuss the numerous advances that would be useful for patients in the daily management of this disease.Please see related article: http://bmcmedicine.biomedcentral.com/articles/ 10.1186/s12916-016-0738-8 .
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Abstract Adult onset Still's disease (AOSD) is a rare inflammatory disorder characterized by hectic spiking fever, evanescent rash and joint involvement. Prognosis is highly variable upon disease ...course and specific involvements, ranging from benign and limited outcome to chronic destructive polyarthritis and/or life-threatening events in case of visceral complications or reactive hemophagocytic lymphohistiocytosis (RHL). AOSD remains a debatable entity at the frontiers of autoimmune diseases and autoinflammatory disorders. The pivotal role of macrophage cell activation leading to a typical Th1 cytokine storm is now well established in AOSD, and confirmed by the benefits using treatments targeting TNF-α, IL-1β or IL-6 in refractory patients. However, it remains difficult to determine predictive factors of outcome and to draw guidelines for patient management. Herein, reviewing literature and relying on our experience in a series of 8 refractory AOSD patients, we question nosology and postulate that different cytokine patterns could underlie contrasting clinical expressions, as well as responses to targeted therapies. We therefore propose to dichotomize AOSD according to its clinical presentation. On the one hand, ‘systemic AOSD’ patients, exhibiting the highest inflammation process driven by excessive IL-18, IL-1β and IL-6 production, would be at risk of life-threatening complications (such as multivisceral involvements and RHL), and would preferentially respond to IL-1β and IL-6 antagonists. On the other hand, ‘rheumatic AOSD’ patients, exhibiting pre-eminence of joint involvement driven by IL-8 and IFN-γ production, would be at risk of articular destructions, and would preferentially respond to TNF-α blockers.
We read with deep interest the report by Tepasse et al .1 concerning two cases of persisting viraemia in coronavirus disease 2019 (COVID‐19) with fatal outcome. Whilst severe acute respiratory ...syndrome coronavirus‐2 (SARS‐CoV‐2) infection in the early stages of infection has been well described, less is known about the development of antibodies to SARS‐CoV‐2, clearance of RNA shedding and clinical outcome of COVID‐19. In addition, the impact of immunosuppressive treatments on disease severity is not yet established, but several reports suggest a more prolonged disease in patients under rituximab, a B‐cell depleting drug.2-4 Here we report a case of persisting COVID‐19, following combined treatment with rituximab and bendamustine for lymphoma, which immediately recovered after convalescent plasma transfusion. We think that this case raises promising perspectives for immunocompromised patients with persisting COVID‐19.
Systemic sclerosis (SSc) is a rare autoimmune disease, which is potentially lethal. The physiopathology of the disease is still incompletely elucidated although the role of fibroblasts, endothelial ...cells (ECs), immune cells. and the environment (i.e., oxidative stress) has been demonstrated. This is an intractable disease with an urgent need to provide better therapeutic options to patients. Mesenchymal stem cells (MSCs) represent a promising therapeutic approach thanks to the number of trophic and pleiotropic properties they exert. Among these, MSCs display anti-fibrotic, angiogenic, and immunomodulatory capacities that might be of interest in the treatment of SSc by acting on different processes that are dysregulated in the disease. In the recent years, the therapeutic effectiveness of MSCs has been demonstrated in different preclinical animal models and is being investigated in phase I clinical trials. Both allogenic and autologous transplantation of MSCs isolated from bone marrow or adipose tissue is being evaluated. The rationale for using allogenic MSCs in SSc, as well as in other autoimmune diseases, is based on the possibility that autologous MSCs might be altered in these diseases. In SSc, reports from the literature are controversial. Nevertheless, the role of the oxidative environment and of the crosstalk with neighboring cells (fibroblasts and ECs) on the functional properties of MSCs has been reported. Here, we review the preclinical and clinical data reporting the interest of MSC-based treatment in SSc and question the use of autologous or allogeneic MSCs in perspective of clinical applications.
In these times of Covid-19 pandemic, during which medical research is mobilized in the fight against the coronavirus, patients continue to suffer from other acute and chronic diseases and research on ...them must continue. Systemic sclerosis (SSc) is one of these diseases, both chronic and complex, whose evolution can be fatal and whose clinical repercussions, variable from one patient to another, can result in a profound alteration of autonomy and quality of life. The current crisis of the coronavirus should not make us forget this reality. At this point, we must recall the well-known generalities about this disease (1). Systemic Sclerosis is a rare multifaceted disease, whose development is related to the interplay of three major pathophysiological mechanisms, i.e. vascular impairment, autoimmunity and uncontrolled fibrogenesis. These mechanisms lead to the development of the main disease-related manifestations including skin, lung, heart, and gastrointestinal tract involvement. Fibrosis primarily affects the skin dermis. However, the lungs, heart, and/or digestive tract may also be involved. Vascular impairment leads to the development of Raynaud's phenomenon, telangiectasia, digital ulcers, pulmonary arterial hypertension and/or vascular renal crisis. These features render SSc a very peculiar autoimmune disorder. Autoimmunity in SSc is mediated via the immune cell activation and production of autoantibodies (Abs). The latter are mainly directed against three target autoantigens, namely Topoisomerase 1 (anti-SCL70 Abs), CENP-A/B (anti-centromere Abs) or RNA-polymerase III. Sustained immune and inflammatory stimulation promote pathological fibroblast activation, which results in excessive extracellular matrix protein production and accumulation in tissues. The clinical presentation of the disease is heterogenous. SSc may present in three classical forms, including limited cutaneous, diffuse cutaneous, and 'sine scleroderma' subsets, and may associate with other connective tissue diseases. SSc has a poor prognosis, globally with a severe vital prognosis and potential long-term disability. Its treatment is mainly palliative and based on symptomatic therapies, vasodilators, immunosuppressants, targeted therapies and antifibrotic drugs. Therefore,
Abstract
Primary Sjögren’s syndrome (pSS) is an autoimmune disease with frequent neurological involvement. Memory complaints are common, but their precise patterns remain unclear. We wanted to ...characterize patterns of neurocognitive profiles in pSS patients with cognitive complaints. Only pSS patients with memory complaints were included, prospectively. Cognitive profiles were compiled through a comprehensive cognitive evaluation by neuropsychologists. Evaluations of anxiety, depression, fatigue, sleep disorders and quality of life were performed for testing their interactions with cognitive profiles. All 32 pSS patients showed at least borderline cognitive impairment, and 17 (53%) exhibited a pathological cognitive profile: a hippocampal profile (37%), a dysexecutive profile (22%), and an instrumental profile (16%) (possible overlap). Regarding the secondary objectives: 37% of patients were depressed, and 48% exhibited a mild-to-severe anxiety trait. Sleep disorders were frequent (excessive daytime sleepiness (55%), high risk for sleep apnea (45%), and insomnia (77%)). Cognitive impairments could not be explained alone by anxiety, depression or sleep disorders. Fatigue level was strongly associated with sleep disorders. Our study highlights that cognitive complaints in pSS patients are supported by measurable cognitive impairments, apart from frequently associated disorders such as depression, anxiety or sleep troubles. Sleep disorders should be screened.
Systemic sclerosis (SSc) is an autoimmune connective tissue disorder, characterized by multisystem involvement, vasculopathy, and fibrosis. An increased risk of malignancy is observed in SSc ...(including breast and lung cancers), and in a subgroup of patients with specific autoantibodies (i.e., anti-RNA polymerase III and related autoantibodies), SSc could be a paraneoplastic syndrome and might be directly related to an immune response against cancer. Herein, we reviewed the literature, focusing on the most recent articles, and shed light onto the potential relationship between cancer and scleroderma regarding temporal and immunological dimensions.
Objective
Systemic sclerosis (SSc) is a rare intractable disease with unmet medical need and fibrosis‐related mortality. Absence of efficient treatments has prompted the development of novel ...therapeutic strategies, among which mesenchymal stem cells/stromal cells (MSCs) or progenitor stromal cells appear to be one of the most attractive options. The purpose of this study was to use the murine model of hypochlorite‐induced SSc to investigate the systemic effects of MSCs on the main features of the diffuse form of the disease: skin and lung fibrosis, autoimmunity, and oxidative status.
Methods
We compared the effects of different doses of MSCs (2.5 × 105, 5 × 105, and 106) infused at different time points. Skin thickness was assessed during the experiment. At the time of euthanasia, biologic parameters were quantified in blood and tissues (by enzyme‐linked immunosorbent assay, quantitative reverse transcription–polymerase chain reaction, assessment of collagen content). Assessments of histology and immunostaining were also performed.
Results
A lower expression of markers of fibrosis (Col1, Col3, Tgfb1, and aSma) was observed in both skin and lung following MSC infusion, which was consistent with histologic improvement and was inversely proportional to the injected dose. Importantly, sera from treated mice exhibited lower levels of anti–Scl‐70 autoantibodies and enhanced antioxidant capacity, confirming the systemic effect of MSCs. Of interest, MSC administration was efficient in both the preventive and the curative approach. We further provide evidence that MSCs exerted an antifibrotic role by normalizing extracellular matrix remodeling parameters as well as reducing proinflammatory cytokine levels and increasing antioxidant defenses.
Conclusion
The results of this study demonstrate the beneficial and systemic effects of MSC administration in the HOCl murine model of diffuse SSc, which is a promising finding from a clinical perspective.
Abstract Objective: Recent outcomes enhanced the critical role of glycosylation pattern of autoantibodies in the pathophysiology of antibody-mediated autoimmune diseases. In this review, we discuss ...the critical role of immunoglobulin (Ig) glycosylation on skewing immune response towards a pro- or anti-inflammatory pathway.Methods: A comprehensive search of Pubmed references was completed by hand searching of selected articles.Results: We first described the impact of glycosylation on Ig immune effector functions: antibody-dependent cell-mediated cytotoxicity, complement activation, dendritic cell, macrophage or B-cell activation and maturation, neoantigen formation, or Ig-receptor binding. We then reviewed autoimmune diseases with abnormal Ig glycosylation, trying to understand its role in the pathogenic process. We then discussed the usefulness of monitoring Ig glycosylation as a biomarker of disease activity, as demonstrated in proteinase-3 anti-neutrophil cytoplasmic autoantibodies associated vasculitis. After reporting environmental and immune factors known to affect Ig glycosylation process, we finally evoked therapeutic strategies currently being developed in order to modulate Ig glycosylation pattern and autoimmune disease evolution.Conclusion: This overview on Ig glycosylation mechanisms and impact on immune system modulation is necessary to face new therapeutic approaches of autoimmune diseases.
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