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1.
Biomolecules ; 10(10)2020 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-33053910

RESUMO

Autoimmune/inflammatory syndrome induced by adjuvants (ASIA) was first introduced in 2011 by Shoenfeld et al. and encompasses a cluster of related immune mediated diseases, which develop among genetically prone individuals as a result of adjuvant agent exposure. Since the recognition of ASIA syndrome, more than 4400 documented cases have been reported so far, illustrated by heterogeneous clinical manifestations and severity. In this review, five enigmatic conditions, including sarcoidosis, Sjögren's syndrome, undifferentiated connective tissue disease, silicone implant incompatibility syndrome (SIIS), and immune-related adverse events (irAEs), are defined as classical examples of ASIA. Certainly, these disorders have been described after an adjuvant stimulus (silicone implantation, drugs, infections, metals, vaccines, etc.) among genetically predisposed individuals (mainly the HLA-DRB1 and PTPN22 gene), which induce an hyperstimulation of the immune system resulting in the production of autoantibodies, eventually leading to the development of autoimmune diseases. Circulating autonomic autoantibodies in the sera of patients with silicone breast implants, as well as anatomopathological aspects of small fiber neuropathy in their skin biopsies have been recently described. To our knowledge, these novel insights serve as a common explanation to the non-specific clinical manifestations reported in patients with ASIA, leading to the redefinition of the ASIA syndrome diagnostic criteria.

2.
Sci Rep ; 10(1): 17709, 2020 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-33077771

RESUMO

18F-FDG PET/CT occupies a growing role in the diagnosis of large vessel vasculitis (LVV), illustrating enhanced uptake in the lining of large vessels. A retrospective single center study was conducted of patients who underwent 18F-FDG PET/CT scans between 2009 and 2019 at Sheba Medical Center, Israel. The imaging results were analyzed for evidence of LVV. We reviewed the PET/CT scans of 126 patients and identified 57 studies that either showed evidence of active LVV or that had been performed in patients previously treated for systemic vasculitis. In 6 patients with fevers of unknown origin and elevated inflammatory markers, PET/CT revealed LVV. Six of 13 patients previously treated for systemic vasculitis demonstrated persistent large vessel uptake. LVV was identified in 8 patients with other autoimmune diseases, and in 4 diagnosed with infectious aortitis. In 26 patients who underwent malignancy surveillance, PET/CT revealed more localized large vessel wall inflammation. Our results illustrate that PET/CT may identify large vessel wall inflammation in patients with a suspicion of LVV, and incidentally in patients who undergo malignancy surveillance. PET/CT may also help delineate the presence and extent of vessel inflammation in patients with LVV and in those with other autoimmune diseases.

4.
Am J Reprod Immunol ; : e13331, 2020 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-32893404

RESUMO

PROBLEM: Antibody-mediated autoimmune diseases, such as autoimmune thyroid diseases (ATD), systemic lupus erythematosus (SLE), and antiphospholipid syndrome (APS), often are associated with recurrent fetal loss. One of the ATD is Hashimoto's thyroiditis which recently showed association with complications of pregnancy with increased levels of circulating autoantibodies reactive with epitopes on thyroid tissue such as thyroid peroxidase (anti-TPO). In retrospective study of sera analyses in patients with Hashimoto's thyroiditis, all patients had mainly elevated circulating anti-TPO autoantibodies. AIM: We assessed the potential of human anti-TPO highly positive IgG, derived from patients with Hashimoto's thyroiditis sera associated with complications of pregnancy, to cause directly complications of pregnancy in murine model. METHOD OF STUDY: Naïve ICR female mice, infused intravenously with 100 µg of anti-TPO-positive IgG, showed increased fetal loss and embryo small for date (P < .001) in comparison with mice passively transferred with commercial IgG or PBS. Moreover, we observed embryos small for date in the mice passively transferred with anti-TPO-positive IgG, exemplified by reduced weight of embryos and placentae (P = .001). Histopathological examination revealed delay in fetal development in 50% cases of anti-TPO-positive IgG-treated mice. Importantly, pathological changes in the transition zone, state of glycogen cells, and significant structural changes in the labyrinth part of placenta were observed in all anti-TPO-positive IgG samples. CONCLUSION: The current study shows in the first time, a direct proof of concept, on the association of human TPO-positive IgG from Hashimoto's thyroiditis patients on fetal loss induction in murine model.

5.
Harefuah ; 159(9): 697-702, 2020 Sep.
Artigo em Hebraico | MEDLINE | ID: mdl-32955815

RESUMO

INTRODUCTION: Silicone is a foreign material to our body and therefore, has been found to stimulate the immune system. Silicone breast implants (SBIs), made of silicone polymer, have been used for aesthetic and medical purposes since the 1960s, and were found to trigger acute/chronic inflammation, eventually leading to the formation of fibrotic capsules on the surface of the implant. Silicone implants have been found to be associated with the development of severe and sometimes unexplained clinical manifestations such as: chronic fatigue, sleep and memory problems, widespread pain, dry mouth and eye, depression, arthralgia, myalgia, palpitations, tinnitus and hearing loss, skin rash, hair loss, vision problems, hyperhidrosis, allergic reactions, etc. Furthermore, SBIs have been found to be associated with the development of rheumatologic/autoimmune diseases and the development of rare lymphoma. The FDA has expressed concern over the years about the implications of SBIs and requested that the companies involved provide data of any concern regarding the implants. However, the companies continued to sell the implants without reporting data, as agreed. In October 2019, the FDA recommended boxed warnings describing the dangers facing women applying for SBIs such as lymphoma. Importantly, our lab recently found the presence of autoantibodies against the autonomic nervous system in the blood of women with SBIs, which might explain some of the patients' severe symptoms. Owing to the numerous data that had been accumulated (since 1960s) indicating a direct link between silicone, autoimmune diseases and cancer, we believe that the use of SBIs has been a historical medical error.

6.
Int J Mol Med ; 46(4): 1266-1273, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32945352

RESUMO

The outbreak of the 2019 coronavirus disease (named, COVID­19), caused by the novel SARS­CoV­2 virus, represents a worldwide severe threat to public health. It is of the utmost importance to characterize the immune responses against the SARS­CoV­2 and the mechanisms of hyperinflammation, in order to design better therapeutic strategies for COVID­19. In the present study, a transcriptomic analysis was performed to profile the immune signatures in lung and the bronchoalveolar lavage fluid samples from COVID­19 patients and controls. Our data concordantly revealed increased humoral responses to infection. The elucidation of the host responses to SARS­CoV­2 infection may further improve our understanding of COVID­19 pathogenesis and suggest better therapeutic strategies.


Assuntos
Linfócitos B/imunologia , Betacoronavirus/imunologia , Infecções por Coronavirus/imunologia , Ativação Linfocitária , Pneumonia Viral/imunologia , Transcriptoma , Linfócitos B/metabolismo , Betacoronavirus/fisiologia , Líquido da Lavagem Broncoalveolar , Infecções por Coronavirus/genética , Bases de Dados Factuais , Feminino , Regulação da Expressão Gênica , Redes Reguladoras de Genes , Interações Hospedeiro-Patógeno , Humanos , Pulmão/imunologia , Pulmão/metabolismo , Masculino , Pandemias , Pneumonia Viral/genética
9.
Isr Med Assoc J ; 8(22): 429-434, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32812717

RESUMO

BACKGROUND: Ferritin, the cellular protein storage for iron, has emerged as a key molecule in the immune system, orchestrating the cellular defense against inflammation. At the end of 2019, the novel severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) rapidly spread throughout China and other countries around the world, resulting in a viral pandemic. OBJECTIVES: To evaluate the correlation between ferritin and disease severity in coronavirus disease-2019 (COVID-19). METHODS: In this cross-sectional study, we obtained clinical and laboratory data regarding 39 hospitalized patients with confirmed COVID-19 from two hospitals in Israel. RESULTS: A significant increase in ferritin levels was demonstrated in patients with moderate and severe disease, compared to patients with mild disease (P = 0.006 and 0.005, respectively). Severe patients had significantly higher levels of ferritin (2817.6 ng/ml) than non-severe patients (708.6 ng/ml) P = 0.02. CONCLUSIONS: In this preliminary cross-sectional study, elevated ferritin levels were shown to correlate with disease severity in 39 patients from Israel with confirmed COVID-19 infection. Our results further strengthen the hypothesis that severe COVID-19 disease might be due to an underlying dysregulated hyperimmune response. In order to identify these patients early and prioritized resources, we believe that all patients with COVID-19 should be screened for hyperferritinemia.


Assuntos
Betacoronavirus , Infecções por Coronavirus/diagnóstico , Ferritinas/sangue , Pneumonia Viral/diagnóstico , Índice de Gravidade de Doença , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Infecções por Coronavirus/sangue , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/sangue , Estudos Retrospectivos
11.
ERJ Open Res ; 6(3)2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32802825

RESUMO

Sarcoidosis and tuberculosis share several similar clinical and pathogenic characteristics that make some researchers consider a common pathogenesis for these diseases. Human leukocyte antigen (HLA) genotypes are studied both in sarcoidosis and tuberculosis patients, but to our knowledge, there are no comparative studies of genetic predisposition for sarcoidosis and tuberculosis development. The aim of this review was to analyse the relationship between HLA genotypes and the development of sarcoidosis and tuberculosis. Original and review articles published in various online databases from 1960 to 2019 were studied. The search results showed opposite effects of the HLA genotypes on predisposition to sarcoidosis or tuberculosis. It was revealed that the genotypes predisposing to the development of sarcoidosis (HLA-DRB1*03/07/15) have protective properties against the development of tuberculosis. Moreover, genotypes causing the development of tuberculosis (HLA-DRB1*04) have a protective effect on the development of sarcoidosis. The results of this narrative review of the literature may allude to the existence of genetic predispositions that lead to the development of an antibacterial or autoimmune response to mycobacteria.

12.
Lupus ; 29(11): 1485-1486, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32746683
13.
Lupus ; 29(11): 1336-1345, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32752918

RESUMO

BACKGROUND: Antiphospholipid antibody syndrome (APS) is an autoimmune disease that affects women in childbearing age. In recent years, great improvements were achieved in the management of pregnancies in these women. Prematurity could be an issue in these pregnancies, mainly due to the direct pathogenic effect of antiphospholipid antibodies (aPL) on the placental surface. Maternal IgG aPL can cross the placenta and theoretically interact with the growing fetus; it could reach the fetal brain because of the incompleteness of the fetal blood-brain barrier: whether this can have an effect on brain development is still debated. Neonatal thrombosis episodes have been described in children positive for aPL, not always associated with maternal antibody positivity, suggesting the hypothesis of a possible aPL de novo synthesis in fetus and neonates. METHODS: A keyword-based literature search was conducted. We also described a case of neonatal catastrophic antiphospholipid syndrome (CAPS). RESULTS: Offspring of patients with APS are generally healthy but the occurrence of neonatal thrombosis or minor neurological disorders were reported. CONCLUSIONS: The limited number of the available data on this sensitive issue supports the need for further studies. Clinical follow-up of children of mothers with APS seems to be important to exclude, in the neonatal period, the occurrence of aPL associated pathological events such as thrombosis, and in the long-term, impairment in learning skills or behavioral problems.

14.
Expert Opin Investig Drugs ; 29(10): 1151-1162, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32755494

RESUMO

INTRODUCTION: Systemic lupus erythematosus (SLE) is a chronic disease that is potentially fatal. There is no cure for SLE and the medications used are associated with toxic side effects. In the era of revolutionary emerging novel biologic agents, the design and investigation of targeted therapy for these patients is necessary. Novel therapies under investigation in phase II-III clinical trials showed promising results. Therapies can target various pathways involved in SLE including cytokines, signal transduction inhibitors, B-cell depletion and interference with co-stimulation. Of interest is the proof of concept of sequential therapy. AREAS COVERED: We performed an extensive literature search via PubMed, Medline, Elsevier Science and Springer Link databases between the years 2014-2020 using the following terms: SLE, novel treatments. We have reviewed 232 articles and selected those articles that (i) focus on phase II-III emerging therapies and (ii) offer new findings from existing therapies, which reveal breakthrough concepts in SLE treatment. EXPERT OPINION: It is still difficult to crack the puzzle of a successful SLE treatment approach. New strategies with potential may encompass the targeting of more than one protein. Another way forward is to identify each SLE patient and personalize therapy by clinical manifestations, disease activity, serology and activated protein.

15.
Int J Infect Dis ; 99: 243-244, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32763445
16.
Isr Med Assoc J ; 7(22): 335-337, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32692492

RESUMO

BACKGROUND: There is a high prevalence of olfaction changes, especially in the early presentation, in COVID-19 patients. The mechanisms through which the virus leads to anosmia/hyposmia is still not fully understood. However, olfaction changes could be used as an indication for testing or quarantine. Screening for infections and other diseases by recognizing volatile organic compounds (VOCs) has been previously conducted. Hence, if the coronavirus infection also results in VOCs excretion, physicians could "smell" the virus by using electronic noses. We conducted a literature review on olfaction changes and the COVID-19. Our results suggest that these changes could be used an indication for early testing, even as an isolated symptom. We propose that the electronic nose be used as a future screening tool, especially in agglomeration spaces such as airports, for screening for the COVID-19 infection.


Assuntos
Técnicas de Laboratório Clínico/métodos , Infecções por Coronavirus/diagnóstico , Transtornos do Olfato/virologia , Pneumonia Viral/diagnóstico , Animais , Infecções por Coronavirus/fisiopatologia , Humanos , Programas de Rastreamento/métodos , Pandemias , Pneumonia Viral/fisiopatologia , Prevalência , Olfato/fisiologia
17.
Sci Rep ; 10(1): 12232, 2020 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-32699419

RESUMO

Ferritin is an iron-binding molecule, which comprises 24 subunits, heavy (FeH) and light (FeL) subunits, suggested to have a pathogenic role by the 'hyperferritinemic syndrome'. In this work, we tested (1) FeH and FeL in bone marrow (BM) and sera in patients with macrophage activation syndrome (MAS); (2) pro-inflammatory effects of ferritin, FeL, and FeH on macrophages; (3) ability of FeH-stimulated macrophages to stimulate the proliferation of peripheral blood mononuclear cells (PBMCs); (4) production of mature IL-1ß and IL-12p70 in extracellular compartments of FeH-stimulated macrophages. Immunofluorescence analysis and liquid chromatography mass spectrometry (LC-MS/MS) based proteomics were performed to identify FeL and FeH in BM and sera, respectively, in the same patients. Macrophages were stimulated with ferritin, FeH, and FeL to assess pro-inflammatory effects by RT-PCR and western blot. The proliferation of co-cultured PBMCs with FeH-stimulated macrophages was tested. Immunofluorescence showed an increased FeH expression in BMs, whereas LC-MS/MS identified that FeL was mainly represented in sera. FeH induced a significant increase of gene expressions of IL-1ß, IL-6, IL-12, and TNF-α, more marked with FeH, which also stimulated NLRP3. FeH-stimulated macrophages enhanced the proliferation of PBMCs. The ELISA assays showed that mature form of IL-1ß and IL-12p70 were increased, in extracellular compartments of FeH-stimulated macrophages. Our results showed FeH in BM biopsies of MAS patients, whereas, LC-MS/MS identified FeL in the sera. FeH showed pro-inflammatory effects on macrophages, stimulated NLRP3, and increased PBMCs proliferation.

18.
Harefuah ; 159(7): 508-515, 2020 Jul.
Artigo em Hebraico | MEDLINE | ID: mdl-32720769

RESUMO

INTRODUCTION: In recent years, considerable progress has been achieved in understanding the interaction between malignant cells and immune cells. The immune system continually seeks out and destroys mutated cells, but in some cases, mutations may occur and give some malignant cells the advantage to neutralize and evade the immune system. One of the regulatory mechanisms that allows these cells to abrogate immune responses is based on Immune Checkpoints. These checkpoints include the Cytotoxic-T lymphocyte antigen-4 (CTLA-4), Programmed cell death protein-1 (PD-1) and its ligand Programmed death-ligand-1 (PD-L1). Tasuku Honjo and James Allison, 2018 Nobel Prize laureates, investigated various components of these mechanisms. They found that in some cases malignant cells may overexpress binding sites that interact with CTLA-4 or PD-1, like the PD-L1 molecule, thus managing to maneuver the immune system. They paved the way for a new class of cancer drugs by showing different strategies to disrupt these checkpoints. This understanding has prompted a paradigm shift in oncology and a breakthrough in the development of new generation immunotherapy drugs: Immune Checkpoint Inhibitors (ICPi). By unbalancing the immune system, these treatments also generated dysimmune toxicities, called Immune Related Adverse Events (irAEs). The study of irAEs is in its infancy; there are very few prospective studies. Where possible, the estimates of irAE incidence were drawn from meta-analyses of randomized controlled trials. In this article, we discuss the connection between immune system, autoimmunity and cancer; immune checkpoint inhibitors and associated autoimmune toxicities; the impact of autoimmune manifestations on cancer outcome and management of irAEs.


Assuntos
Antineoplásicos Imunológicos , Imunoterapia , Neoplasias , Antígeno CTLA-4 , Humanos , Fatores Imunológicos , Estudos Prospectivos
19.
Immunol Res ; 68(4): 213-224, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32681497

RESUMO

SARS-CoV-2 infection is characterized by a protean clinical picture that can range from asymptomatic patients to life-threatening conditions. Severe COVID-19 patients often display a severe pulmonary involvement and develop neutrophilia, lymphopenia, and strikingly elevated levels of IL-6. There is an over-exuberant cytokine release with hyperferritinemia leading to the idea that COVID-19 is part of the hyperferritinemic syndrome spectrum. Indeed, very high levels of ferritin can occur in other diseases including hemophagocytic lymphohistiocytosis, macrophage activation syndrome, adult-onset Still's disease, catastrophic antiphospholipid syndrome and septic shock. Numerous studies have demonstrated the immunomodulatory effects of ferritin and its association with mortality and sustained inflammatory process. High levels of free iron are harmful in tissues, especially through the redox damage that can lead to fibrosis. Iron chelation represents a pillar in the treatment of iron overload. In addition, it was proven to have an anti-viral and anti-fibrotic activity. Herein, we analyse the pathogenic role of ferritin and iron during SARS-CoV-2 infection and propose iron depletion therapy as a novel therapeutic approach in the COVID-19 pandemic.


Assuntos
Betacoronavirus/metabolismo , Infecções por Coronavirus , Ferritinas/sangue , Quelantes de Ferro/uso terapêutico , Sobrecarga de Ferro , Ferro/sangue , Pandemias , Pneumonia Viral , Infecções por Coronavirus/sangue , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/epidemiologia , Humanos , Sobrecarga de Ferro/sangue , Sobrecarga de Ferro/tratamento farmacológico , Sobrecarga de Ferro/epidemiologia , Pneumonia Viral/sangue , Pneumonia Viral/tratamento farmacológico , Pneumonia Viral/epidemiologia
20.
Autoimmun Rev ; 19(9): 102618, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32663621

RESUMO

This document follows up on a 2017 revised international consensus on anti-neutrophil cytoplasm antibodies (ANCA) testing in granulomatosis with polyangiitis and microscopic polyangiitis and focuses on the clinical and diagnostic value of ANCA detection in patients with connective tissue diseases, idiopathic interstitial pneumonia, autoimmune liver diseases, inflammatory bowel diseases, anti-glomerular basement membrane (GBM) disease, infections, malignancy, and during drug treatment. Current evidence suggests that in certain settings beyond systemic vasculitis, ANCA may have clinical, pathogenic and/or diagnostic relevance. Antigen-specific ANCA targeting proteinase-3 and myeloperoxidase should be tested by solid phase immunoassays in any patient with clinical features suggesting ANCA-associated vasculitis and in all patients with anti-GBM disease, idiopathic interstitial pneumonia, and infective endocarditis associated with nephritis, whereas in patients with other aforementioned disorders routine ANCA testing is not recommended. Among patients with autoimmune liver diseases or inflammatory bowel diseases, ANCA testing may be justified in patients with suspected autoimmune hepatitis type 1 who do not have conventional autoantibodies or in case of diagnostic uncertainty to discriminate ulcerative colitis from Crohn's disease. In these cases, ANCA should be tested by indirect immunofluorescence as the target antigens are not yet well characterized. Many questions concerning the optimal use of ANCA testing in patients without ANCA-associated vasculitis remain to be answered.


Assuntos
Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos , Anticorpos Anticitoplasma de Neutrófilos/análise , Consenso , Granulomatose com Poliangiite/imunologia , Hepatite Autoimune/imunologia , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/imunologia , Humanos , Mieloblastina/imunologia , Peroxidase/imunologia
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