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1.
Rev. Hosp. Ital. B. Aires (2004) ; 40(4): 199-207, dic. 2020. ilus, tab
Artigo em Espanhol | LILACS | ID: biblio-1145501

RESUMO

La encefalitis límbica es una enfermedad infrecuente y potencialmente grave, que puede o no ser paraneoplásica y se caracteriza por déficit de la memoria reciente, alteraciones psiquiátricas y convulsiones. De origen autoinmunitario, está asociada a anticuerpos séricos e intratecales contra antígenos neuronales intracelulares y de superficie, con especial afectación de zonas límbicas. En este artículo se revisan aspectos históricos y epidemiológicos, patogenia, síndromes más frecuentes y mejor delimitados, histopatología y estudios complementarios. Se repasan también las dificultades del diagnóstico diferencial y la necesidad de descartar siempre un tumor subyacente. La detección de autoanticuerpos neuronales es importante para el diagnóstico, la planificación terapéutica y el pronóstico. La inmunoterapia y, si corresponde, el tratamiento de la neoplasia son cruciales para lograr una recuperación neurológica sustancial. La encefalitis límbica es una entidad probablemente subdiagnosticada, con un pronóstico más favorable si se trata de forma temprana. El actual conocimiento de su patogenia puede además aportar claridad para la mejor comprensión de otros síndromes neurológicos y psiquiátricos que puedan compartir mecanismos autoinmunitarios, como algunos trastornos psicóticos y epilepsias farmacorresistentes. (AU)


Limbic encephalitis is a rare and potentially serious disease, which may or may not be paraneoplastic and is characterized by recent memory deficits, psychiatric disturbances and seizures. Of autoimmune origin, it is associated with serum and intrathecal antibodies against intracellular and surface neuronal antigens, with special involvement of limbic areas. This article reviews historical and epidemiological aspects, pathogenesis, more frequent and better defined syndromes, histopathology and complementary studies. The difficulties of differential diagnosis and the need to always rule out an underlying tumor are also reviewed. Detection of neuronal autoantibodies is important for diagnosis, therapeutic planning and prognosis. Immunotherapy and, if appropriate, neoplasm treatment, are crucial to achieve substantial neurological recovery. Limbic encephalitis is probably an underdiagnosed entity, with a more favorable prognosis if treated early. The current knowledge of its pathogenesis may also provide clarity for a better understanding of other neurological and psychiatric syndromes that may share autoimmune mechanisms, such as some psychotic disorders and drug-resistant epilepsies. (AU)


Assuntos
Humanos , Autoanticorpos/metabolismo , Doenças Autoimunes/patologia , Síndromes Paraneoplásicas do Sistema Nervoso/patologia , Encefalite Límbica/patologia , Transtornos Psicóticos/diagnóstico , Transtornos Psicóticos/etiologia , Doenças Autoimunes/diagnóstico , Doenças Autoimunes/etiologia , Doenças Autoimunes/terapia , Literatura de Revisão como Assunto , Síndromes Paraneoplásicas do Sistema Nervoso/diagnóstico , Síndromes Paraneoplásicas do Sistema Nervoso/etiologia , Síndromes Paraneoplásicas do Sistema Nervoso/terapia , Encefalite Límbica/diagnóstico , Encefalite Límbica/etiologia , Encefalite Límbica/história , Encefalite Límbica/terapia , Epilepsia/diagnóstico , Epilepsia/etiologia
2.
Zhongguo Yi Xue Ke Xue Yuan Xue Bao ; 42(5): 702-705, 2020 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-33131528

RESUMO

This article summarizes the clinical features and follow-up findings of insulin autoimmune syndrome in two patients with type 2 diabetes after the use of lipoic acid,along with literature review,with an attempt to increase the awareness of lipoic acid-induced insulin autoimmune syndrome among clinicians and improve its diagnosis and treatment.


Assuntos
Doenças Autoimunes , Diabetes Mellitus Tipo 2 , Doenças Autoimunes/induzido quimicamente , Doenças Autoimunes/complicações , Doenças Autoimunes/tratamento farmacológico , Doenças Autoimunes/patologia , Diabetes Mellitus Tipo 2/complicações , Humanos , Ácido Tióctico/efeitos adversos
3.
PLoS One ; 15(11): e0242443, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33216776

RESUMO

Idiopathic Inflammatory Myopathies (IIMs) have been studied within the framework of autoimmune diseases where skeletal muscle appears to have a passive role in the illness. However, persiting weakness even after resolving inflammation raises questions about the role that skeletal muscle plays by itself in these diseases. "Non-immune mediated" hypotheses have arisen to consider inner skeletal muscle cell processes as trigger factors in the clinical manifestations of IIMs. Alterations in oxidative phosphorylation, ATP production, calcium handling, autophagy, endoplasmic reticulum stress, among others, have been proposed as alternative cellular pathophysiological mechanisms. In this study, we used skeletal muscle-derived cells, from healthy controls and IIM patients to determine mitochondrial function and mitochondrial ability to adapt to a metabolic stress when deprived of glucose. We hypothesized that mitochondria would be dysfunctional in IIM samples, which was partially true in normal glucose rich growing medium as determined by oxygen consumption rate. However, in the glucose-free and galactose supplemented condition, a medium that forced mitochondria to function, IIM cells increased their respiration, reaching values matching normal derived cells. Unexpectedly, cell death significantly increased in IIM cells under this condition. Our findings show that mitochondria in IIM is functional and the decrease respiration observed is part of an adaptative response to improve survival. The increased metabolic function obtained after forcing IIM cells to rely on mitochondrial synthesized ATP is detrimental to the cell's viability. Thus, therapeutic interventions that activate mitochondria, could be detrimental in IIM cell physiology, and must be avoided in patients with IIM.


Assuntos
Apoptose/fisiologia , Mitocôndrias/metabolismo , Músculo Esquelético/metabolismo , Mioblastos/patologia , Miosite/patologia , Trifosfato de Adenosina/análise , Idoso , Autoanticorpos/imunologia , Doenças Autoimunes/patologia , Células Cultivadas , Estresse do Retículo Endoplasmático/fisiologia , Feminino , Humanos , Masculino , Potencial da Membrana Mitocondrial/fisiologia , Pessoa de Meia-Idade , Fosforilação Oxidativa , Estresse Oxidativo/fisiologia , Espécies Reativas de Oxigênio/metabolismo
4.
Nat Genet ; 52(10): 1036-1045, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32929287

RESUMO

We report on the influence of ~22 million variants on 731 immune cell traits in a cohort of 3,757 Sardinians. We detected 122 significant (P < 1.28 × 10-11) independent association signals for 459 cell traits at 70 loci (53 of them novel) identifying several molecules and mechanisms involved in cell regulation. Furthermore, 53 signals at 36 loci overlapped with previously reported disease-associated signals, predominantly for autoimmune disorders, highlighting intermediate phenotypes in pathogenesis. Collectively, our findings illustrate complex genetic regulation of immune cells with highly selective effects on autoimmune disease risk at the cell-subtype level. These results identify drug-targetable pathways informing the design of more specific treatments for autoimmune diseases.


Assuntos
Doenças Autoimunes/genética , Autoimunidade/genética , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Doenças Autoimunes/tratamento farmacológico , Doenças Autoimunes/epidemiologia , Doenças Autoimunes/patologia , Humanos , Itália/epidemiologia , Fenótipo , Polimorfismo de Nucleotídeo Único/genética
5.
Nat Rev Drug Discov ; 19(10): 695-710, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32873970

RESUMO

Historically, the main classes of drug targets have been receptors, enzymes, ion channels and transporters. However, owing largely to the rise of antibody-based therapies in the past two decades, soluble protein ligands such as inflammatory cytokines have become an increasingly important class of drug targets. In this Review, we analyse drugs targeting ligands that have reached clinical development at some point since 1992. We identify 291 drugs that target 99 unique ligands, and we discuss trends in the characteristics of the ligands, drugs and indications for which they have been tested. In the last 5 years, the number of ligand-targeting drugs approved by the FDA has doubled to 34, while the number of clinically validated ligand targets has doubled to 22. Cytokines and growth factors are the predominant types of targeted ligands (70%), and inflammation and autoimmune disorders, cancer and ophthalmological diseases are the top therapeutic areas for both approved agents and agents in clinical studies, reflecting the central role of cytokine and/or growth factor pathways in such diseases.


Assuntos
Doenças Autoimunes/tratamento farmacológico , Citocinas/antagonistas & inibidores , Descoberta de Drogas , Inflamação/tratamento farmacológico , Peptídeos e Proteínas de Sinalização Intercelular/química , Neoplasias/tratamento farmacológico , Preparações Farmacêuticas/metabolismo , Doenças Autoimunes/metabolismo , Doenças Autoimunes/patologia , Citocinas/metabolismo , Desenho de Fármacos , Humanos , Inflamação/metabolismo , Inflamação/patologia , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Ligantes , Neoplasias/metabolismo , Neoplasias/patologia
6.
Proc Natl Acad Sci U S A ; 117(40): 25008-25017, 2020 10 06.
Artigo em Inglês | MEDLINE | ID: mdl-32968020

RESUMO

IL-17A is a therapeutic target in many autoimmune diseases. Most nonhematopoietic cells express IL-17A receptors and respond to extracellular IL-17A by inducing proinflammatory cytokines. The IL-17A signal transduction triggers two broad, TRAF6- and TRAF5-dependent, intracellular signaling pathways to produce representative cytokines (IL-6) and chemokines (CXCL-1), respectively. Our limited understanding of the cross-talk between these two branches has generated a crucial gap of knowledge, leading to therapeutics indiscriminately blocking IL-17A and global inhibition of its target genes. In previous work, we discovered an elevated expression of 14-3-3 proteins in inflammatory aortic disease, a rare human autoimmune disorder with increased levels of IL-17A. Here we report that 14-3-3ζ is essential for IL-17 signaling by differentially regulating the signal-induced IL-6 and CXCL-1. Using genetically manipulated human and mouse cells, and ex vivo and in vivo rat models, we uncovered a function of 14-3-3ζ. As a part of the molecular mechanism, we show that 14-3-3ζ interacts with several TRAF proteins; in particular, its interaction with TRAF5 and TRAF6 is increased in the presence of IL-17A. In contrast to TRAF6, we found TRAF5 to be an endogenous suppressor of IL-17A-induced IL-6 production, an effect countered by 14-3-3ζ. Furthermore, we observed that 14-3-3ζ interaction with TRAF proteins is required for the IL-17A-induced IL-6 levels. Together, our results show that 14-3-3ζ is an essential component of IL-17A signaling and IL-6 production, an effect that is suppressed by TRAF5. To the best of our knowledge, this report of the 14-3-3ζ-TRAF5 axis, which differentially regulates IL-17A-induced IL-6 and CXCL-1 production, is unique.


Assuntos
Doenças Autoimunes/genética , Quimiocina CXCL1/genética , Interleucina-17/genética , Interleucina-6/genética , Proteínas 14-3-3/genética , Animais , Doenças Autoimunes/patologia , Quimiocinas/genética , Citocinas/genética , Regulação da Expressão Gênica/genética , Humanos , Camundongos , Ratos , Transdução de Sinais/genética , Fator 5 Associado a Receptor de TNF/genética , Fator 6 Associado a Receptor de TNF/genética
7.
Am J Pathol ; 190(10): 2000-2012, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32745461

RESUMO

Regulatory T cells (Tregs) are non-redundant mediators of immune tolerance that are critical to prevent autoimmune disease and promote an anti-inflammatory tissue environment. Many individuals experience chronic diseases and physiologic changes associated with aging requiring long-term medication. Unfortunately, adverse effects accompany every pharmacologic intervention and may affect overall outcomes. We focus on medications typically prescribed during the treatment of prevalent chronic diseases and disorders, including cardiovascular disease, autoimmune disease, and menopausal symptoms, that affect >200 million individuals in the United States. Increasing studies continue to report that treatment of patients with estrogen, metformin, statins, vitamin D, and tumor necrosis factor blockers are unintentionally modulating the Treg compartment. Effects of these medications likely comprise direct and/or indirect interaction with Tregs via other immune and parenchymal populations. Differing and sometimes opposing effects on the Treg compartment have been observed using the same medication. The length of treatment, dosing regimen and stage of disease, patient age, ethnicity, and sex may account for such findings and determine the specific signaling pathways affected by the medication. Enhancing the Treg compartment can skew the patient's immune system toward an anti-inflammatory phenotype and therefore could provide unanticipated benefit. Currently, multiple medicines prescribed to large numbers of patients influence the Treg compartment; however, how such effects affect their disease outcome and long-term health remains unclear.


Assuntos
Doenças Autoimunes/imunologia , Doenças Autoimunes/patologia , Fatores Imunológicos/metabolismo , Linfócitos T Reguladores/imunologia , Anti-Inflamatórios/farmacologia , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/metabolismo , Tolerância Imunológica/efeitos dos fármacos , Tolerância Imunológica/imunologia , Fatores Imunológicos/farmacologia , Linfócitos T Reguladores/efeitos dos fármacos , Vitamina D/metabolismo
8.
Mayo Clin Proc ; 95(10): 2144-2149, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32807522

RESUMO

OBJECTIVE: To characterize the cardiorespiratory abnormalities in patients with necrotizing autoimmune myopathy (NAM). PATIENTS AND METHODS: Cardiopulmonary features of patients with NAM evaluated in our neuromuscular clinic (January 1, 2004, to September 20, 2018) were reviewed retrospectively with respect to autoantibody status and history of cardiac disease. Clinical characteristics and laboratory findings were compared among patient subgroups. RESULTS: We identified 109 patients with NAM: 36 anti-3-hydroxy-3-methylglutaryl coenzyme A reductase autoantibody (anti-HMGCR Ab)-positive, 18 anti-signal recognition particle antibody (anti-SRP Ab)-positive (3 dual anti-HMGCR/anti-SRP Ab-positive), and 58 seronegative. Median age at diagnosis was 60 years (range, 18-86 years). Forty-three patients had dyspnea at presentation and 32 patients had preexisting risk for cardiac disease (10 coronary artery disease and 28 hypertension). The electrocardiogram was abnormal in 55 of 86 patients (33 without cardiac risk factors), including prolonged corrected QT interval (QTc) (n=31), conduction blocks (n=19), and atrial or ventricular ectopic beats (n=10). Echocardiography was abnormal in 34 of 72 patients, including 19 of 45 without preexisting cardiac disease risks. Echocardiographic abnormalities included left ventricular diastolic dysfunction (n=31) and systolic dysfunction (n=8). The left ventricular diastolic dysfunction improved in 4 of 11 patients after treatment. Pulmonary function testing showed changes suggestive of neuromuscular respiratory muscle weakness in 51 of 66 patients and reduced carbon monoxide diffusing capacity in 11 of 35 patients. However, only 6 patients had radiographic evidence of interstitial lung disease (2 anti-HMGCR Ab-positive and 4 seronegative). Overnight oximetry revealed desaturations in 24 of 38 patients. Six patients required mechanical ventilation and 7 required noninvasive ventilatory support. CONCLUSION: Most patients with NAM exhibited cardiac and respiratory muscle dysfunction. Immunotherapy can improve echocardiographic abnormalities. Interstitial lung disease was rarely identified. Formal evaluation of cardiac and respiratory status should be integral in assessment of patients with NAM.


Assuntos
Doenças Autoimunes/complicações , Cardiopatias/etiologia , Músculo Esquelético/patologia , Doenças Musculares/complicações , Doenças Musculares/imunologia , Transtornos Respiratórios/etiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Doenças Autoimunes/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Doenças Musculares/patologia , Necrose , Estudos Retrospectivos , Adulto Jovem
9.
Proc Natl Acad Sci U S A ; 117(35): 21512-21518, 2020 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-32817492

RESUMO

Multiple sclerosis (MS) is a chronic autoimmune disease of the central nervous system (CNS), with characteristic inflammatory lesions and demyelination. The clinical benefit of cell-depleting therapies targeting CD20 has emphasized the role of B cells and autoantibodies in MS pathogenesis. We previously introduced an enzyme-linked immunospot spot (ELISpot)-based assay to measure CNS antigen-specific B cells in the blood of MS patients and demonstrated its usefulness as a predictive biomarker for disease activity in measuring the successful outcome of disease-modifying therapies (DMTs). Here we used a planar protein array to investigate CNS-reactive antibodies in the serum of MS patients as well as in B cell culture supernatants after polyclonal stimulation. Anti-CNS antibody reactivity was evident in the sera of the MS cohort, and the antibodies bound a heterogeneous set of molecules, including myelin, axonal cytoskeleton, and ion channel antigens, in individual patients. Immunoglobulin reactivity in supernatants of stimulated B cells was directed against a broad range of CNS antigens. A group of MS patients with a highly active B cell component was identified by the ELISpot assay. Those antibody reactivities remained stable over time. These assays with protein arrays identify MS patients with a highly active B cell population with antibodies directed against a swathe of CNS proteins.


Assuntos
Autoanticorpos/imunologia , Linfócitos B/imunologia , Esclerose Múltipla/imunologia , Adulto , Antígenos , Doenças Autoimunes/patologia , Sistema Nervoso Central/imunologia , Sistema Nervoso Central/metabolismo , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Bainha de Mielina/metabolismo
10.
Am J Clin Pathol ; 154(6): 761-766, 2020 11 04.
Artigo em Inglês | MEDLINE | ID: mdl-32632455

RESUMO

OBJECTIVES: Autoimmune metaplastic atrophic gastritis (AMAG) is an underrecognized entity, especially in its early stage. This study assessed whether the use of gastrin immunohistochemistry would increase sensitivity for diagnosing early AMAG. METHODS: Three-hundred gastric biopsies were prospectively stained for gastrin by immunohistochemistry. Inclusion criteria included well-oriented gastric mucosa with mucus glands and minimal plasma cell infiltrate not suspected to represent pyloric metaplasia. Patient age, sex, designated location of biopsy, presence or absence of intestinal metaplasia, and clinical information were not criteria. Any case with absence of gastrin-positive endocrine cells reflexed to chromogranin immunohistochemistry. Maloriented biopsies or cases with current Helicobacter infection were excluded. RESULTS: The 298-patient study cohort comprised 222 females (mean age, 47 years; range, 16-80 years) and 76 males (mean age, 49 years; range, 7-80 years). Biopsies were designated as "antral/antral nodules" (61%), and the rest were labeled "gastric/random stomach" (39%). Nine cases (3%) exhibited absence of gastrin-positive endocrine cells; one of those showed endocrine cell hyperplasia by chromogranin staining. CONCLUSIONS: Pathologists should be aware of the histologic features of early AMAG and meticulously analyze tissue regardless of specimen labeling. Gastrin immunostain is a supplemental diagnostic tool when encountering inflamed antral-appearing specimens.


Assuntos
Mucosa Gástrica/química , Gastrinas/análise , Gastrite Atrófica/diagnóstico , Gastrite Atrófica/patologia , Antro Pilórico/química , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Doenças Autoimunes/diagnóstico , Doenças Autoimunes/patologia , Biópsia , Criança , Diagnóstico Diferencial , Reações Falso-Negativas , Feminino , Mucosa Gástrica/patologia , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Antro Pilórico/patologia , Adulto Jovem
11.
J Med Chem ; 63(21): 12526-12541, 2020 11 12.
Artigo em Inglês | MEDLINE | ID: mdl-32696648

RESUMO

Autoreactive B cell-derived antibodies form immune complexes that likely play a pathogenic role in autoimmune diseases. In systemic lupus erythematosus (SLE), these antibodies bind Fc receptors on myeloid cells and induce proinflammatory cytokine production by monocytes and NETosis by neutrophils. Bruton's tyrosine kinase (BTK) is a non-receptor tyrosine kinase that signals downstream of Fc receptors and plays a transduction role in antibody expression following B cell activation. Given the roles of BTK in both the production and sensing of autoreactive antibodies, inhibitors of BTK kinase activity may provide therapeutic value to patients suffering from autoantibody-driven immune disorders. Starting from an in-house proprietary screening hit followed by structure-based rational design, we have identified a potent, reversible BTK inhibitor, BIIB068 (1), which demonstrated good kinome selectivity with good overall drug-like properties for oral dosing, was well tolerated across preclinical species at pharmacologically relevant doses with good ADME properties, and achieved >90% inhibition of BTK phosphorylation (pBTK) in humans.


Assuntos
Tirosina Quinase da Agamaglobulinemia/antagonistas & inibidores , Inibidores de Proteínas Quinases/química , Pirimidinas/química , Administração Oral , Tirosina Quinase da Agamaglobulinemia/metabolismo , Animais , Antígenos T-Independentes/química , Antígenos T-Independentes/metabolismo , Doenças Autoimunes/tratamento farmacológico , Doenças Autoimunes/imunologia , Doenças Autoimunes/patologia , Sítios de Ligação , Domínio Catalítico , Cães , Avaliação Pré-Clínica de Medicamentos , Feminino , Meia-Vida , Humanos , Camundongos , Microssomos Hepáticos/metabolismo , Simulação de Dinâmica Molecular , Inibidores de Proteínas Quinases/metabolismo , Inibidores de Proteínas Quinases/uso terapêutico , Pirimidinas/metabolismo , Pirimidinas/uso terapêutico , Ratos , Relação Estrutura-Atividade
12.
Autoimmun Rev ; 19(9): 102617, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32663626

RESUMO

The role of the cytokines and receptors of the IL-1 family in inflammation is well known. Several cytokines of the family have a powerful inflammatory activity, with IL-1ß being the best-characterized factor. The inflammatory activity of IL-1 cytokines is regulated by other factors of the family, including receptor antagonists, soluble receptors and anti-inflammatory cytokines. The causative role of IL-1ß is well-established in autoinflammatory diseases, mainly due to gain-of-function mutations in genes encoding the IL-1ß-maturing inflammasome. Exaggerated production of IL-1ß and IL-18 correlates with disease and disease severity also in several autoimmune and chronic inflammatory and degenerative pathologies, although it is not clear whether they have a causative role or are only involved in the downstream disease symptoms. A better understanding of the pathological role of IL-1 family cytokines in autoimmunity involves a deeper evaluation, in the pathological situations, of the possible anomalies in the feed-back anti-inflammatory mechanisms that in physiological reactions control and dump IL-1-mediated inflammation. Thus, we expect that IL-1 cytokines may be pathogenic only when, in addition to enhanced production, there is a concomitant failure of their control mechanisms. In this review we will examine the current knowledge on the role of IL-1 family cytokines in autoimmune and chronic inflammatory and degenerative diseases, with a particular focus on their endogenous control mechanisms, mainly based on soluble receptors/inhibitors and receptor antagonists. This will allow us to formulate a knowledge-based hypothesis on the involvement of IL-1 cytokines in the pathogenesis vs. the clinical features of these diseases.


Assuntos
Doenças Autoimunes/imunologia , Interleucina-1/classificação , Interleucina-1/imunologia , Doenças Autoimunes/patologia , Autoimunidade , Humanos , Inflamassomos , Inflamação
14.
Semin Cancer Biol ; 64: 102-107, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32522353

RESUMO

Since the discovery of the first microRNA (miRNA) in 1993, thousands of miRNAs have been identified in humans and mice and many of them have been shown to control a large variety of cellular processes in different cell types including those composing the immune system. MicroRNAs regulate virtually all aspects of immune cell development, differentiation and function. Studies have shown that these molecules are involved in the maintenance of lymphocyte tolerance and, when dysregulated, promote the development of autoimmune diseases. In this review, we focus on the current knowledge about the roles of miRNAs in B cell tolerance and their contribution to autoimmunity, highlighting additional roles for some of these miRNAs in T cell tolerance. Finally, we will comment on miRNAs that promote both autoimmunity and lymphoma.


Assuntos
Doenças Autoimunes/imunologia , Linfócitos B/imunologia , Tolerância Imunológica/imunologia , MicroRNAs/genética , Neoplasias/imunologia , Animais , Doenças Autoimunes/genética , Doenças Autoimunes/patologia , Linfócitos B/metabolismo , Humanos , Tolerância Imunológica/genética , Neoplasias/genética , Neoplasias/patologia
15.
PLoS One ; 15(6): e0234813, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32555638

RESUMO

BACKGROUND: Autoimmune conditions (AICs) and/or their treatment may alter risk of human papilloma virus (HPV) infection and females with AICs are therefore at an increased risk of cervical dysplasia. However, inclusion of these at-risk populations in cervical cancer screening and HPV-vaccination guidelines, are mostly lacking. This study aimed to determine the prevalence of cervical dysplasia in a wide range of AICs and compare that to HIV and immunocompetent controls to support the optimisation of cervical cancer preventive health measures. METHODS: Data linkage was used to match cervical screening episodes to emergency department records of females with AICs or HIV to immunocompetent controls over a 14-year period. The primary outcome was histologically confirmed high-grade cervical disease. Results, measured as rates by cytology and histology classification per 1,000 females screened, were analysed per disease group, and intergroup comparisons were performed. RESULTS: Females with inflammatory bowel disease (2,683), psoriatic and enteropathic arthropathies (1,848), multiple sclerosis (MS) (1,426), rheumatoid arthritis (1,246), systemic lupus erythematosus and/or mixed connective tissue disease (SLE/MCTD) (702), HIV (44), and 985,383 immunocompetent controls were included. SLE/MCTD and HIV groups had greater rates of high-grade histological and cytological abnormalities compared to controls. Increased rates of low-grade cytological abnormalities were detected in all females with AICs, with the exception of the MS group. CONCLUSIONS: Females with SLE/MCTD or HIV have increased rates of high-grade cervical abnormalities. The increased low-grade dysplasia rate seen in most females with AICs is consistent with increased HPV infection. These findings support expansion of cervical cancer preventative programs to include these at-risk females.


Assuntos
Doenças Autoimunes/patologia , Displasia do Colo do Útero/patologia , Adulto , Artrite Reumatoide/complicações , Artrite Reumatoide/patologia , Austrália/epidemiologia , Doenças Autoimunes/complicações , Bases de Dados Factuais , Feminino , Infecções por HIV/complicações , Infecções por HIV/patologia , Humanos , Imunocompetência , Lúpus Eritematoso Sistêmico/complicações , Lúpus Eritematoso Sistêmico/patologia , Pessoa de Meia-Idade , Gradação de Tumores , Prevalência , Fatores de Risco , Displasia do Colo do Útero/complicações , Displasia do Colo do Útero/epidemiologia
16.
Int J Mol Sci ; 21(9)2020 May 08.
Artigo em Inglês | MEDLINE | ID: covidwho-209974

RESUMO

On 7 January 2020, researchers isolated and sequenced in China from patients with severe pneumonitis a novel coronavirus, then called SARS-CoV-2, which rapidly spread worldwide, becoming a global health emergency. Typical manifestations consist of flu-like symptoms such as fever, cough, fatigue, and dyspnea. However, in about 20% of patients, the infection progresses to severe interstitial pneumonia and can induce an uncontrolled host-immune response, leading to a life-threatening condition called cytokine release syndrome (CRS). CRS represents an emergency scenario of a frequent challenge, which is the complex and interwoven link between infections and autoimmunity. Indeed, treatment of CRS involves the use of both antivirals to control the underlying infection and immunosuppressive agents to dampen the aberrant pro-inflammatory response of the host. Several trials, evaluating the safety and effectiveness of immunosuppressants commonly used in rheumatic diseases, are ongoing in patients with COVID-19 and CRS, some of which are achieving promising results. However, such a use should follow a multidisciplinary approach, be accompanied by close monitoring, be tailored to patient's clinical and serological features, and be initiated at the right time to reach the best results. Autoimmune patients receiving immunosuppressants could be prone to SARS-CoV-2 infections; however, suspension of the ongoing therapy is contraindicated to avoid disease flares and a consequent increase in the infection risk.


Assuntos
Antivirais/uso terapêutico , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/imunologia , Síndrome da Liberação de Citocina/patologia , Pneumonia Viral/tratamento farmacológico , Pneumonia Viral/imunologia , Doenças Autoimunes/complicações , Doenças Autoimunes/tratamento farmacológico , Doenças Autoimunes/patologia , Betacoronavirus/fisiologia , Ensaios Clínicos como Assunto , Infecções por Coronavirus/complicações , Infecções por Coronavirus/patologia , Síndrome da Liberação de Citocina/tratamento farmacológico , Síndrome da Liberação de Citocina/imunologia , Humanos , Imunossupressores/uso terapêutico , Pandemias , Pneumonia Viral/complicações , Pneumonia Viral/patologia
17.
Crit Rev Oncol Hematol ; 150: 102945, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32353704

RESUMO

Autoimmune disorders are a spectrum of diseases caused by impaired self-tolerance of the immune system. Previous studies underscored the association between autoimmune disorders and lymphomas. However, only a few papers studied the exact mechanisms of this association. The effect of IL-2, IL-5, IL-6, IL-10 and TNF-α, contribution of NOTCH, FAS and MHC receptor families, the interplay of various immune cells, and the relation of immunosuppressive agents and development of autoimmune disorders are the proposed mechanisms for this association. Each individual autoimmune disorder associates with particular types of lymphomas and their common pathways are not necessarily similar to other pairs of autoimmune disorder-lymphomas. Thus, the lymphomas susceptibility in various autoimmune disorders could not be investigated through a single pathway. In this review, we demonstrate the association between each pair of autoimmune disorder-lymphoma and the underlying pathways. By clarifying these associations, follow-up plans could be made leading to early diagnosis of lymphomas.


Assuntos
Doenças Autoimunes/complicações , Imunossupressores/uso terapêutico , Linfoma não Hodgkin/complicações , Linfoma/etiologia , Doenças Autoimunes/tratamento farmacológico , Doenças Autoimunes/patologia , Humanos , Linfoma não Hodgkin/tratamento farmacológico , Linfoma não Hodgkin/patologia
18.
Immunity ; 52(5): 872-884.e5, 2020 05 19.
Artigo em Inglês | MEDLINE | ID: mdl-32433950

RESUMO

Some endocrine organs are frequent targets of autoimmune attack. Here, we addressed the origin of autoimmune disease from the viewpoint of feedback control. Endocrine tissues maintain mass through feedback loops that balance cell proliferation and removal according to hormone-driven regulatory signals. We hypothesized the existence of a dedicated mechanism that detects and removes mutant cells that missense the signal and therefore hyperproliferate and hypersecrete with potential to disrupt organismal homeostasis. In this mechanism, hypersecreting cells are preferentially eliminated by autoreactive T cells at the cost of a fragility to autoimmune disease. The "autoimmune surveillance of hypersecreting mutants" (ASHM) hypothesis predicts the presence of autoreactive T cells in healthy individuals and the nature of self-antigens as peptides from hormone secretion pathway. It explains why some tissues get prevalent autoimmune disease, whereas others do not and instead show prevalent mutant-expansion disease (e.g., hyperparathyroidism). The ASHM hypothesis is testable, and we discuss experimental follow-up.


Assuntos
Doenças Autoimunes/imunologia , Diabetes Mellitus Tipo 1/imunologia , Glândulas Endócrinas/imunologia , Sistema Endócrino/imunologia , Vigilância Imunológica/imunologia , Animais , Doenças Autoimunes/genética , Doenças Autoimunes/patologia , Proliferação de Células/genética , Proliferação de Células/fisiologia , Diabetes Mellitus Tipo 1/genética , Diabetes Mellitus Tipo 1/patologia , Glândulas Endócrinas/citologia , Glândulas Endócrinas/metabolismo , Sistema Endócrino/citologia , Sistema Endócrino/metabolismo , Feminino , Humanos , Vigilância Imunológica/genética , Masculino , Mutação , Linfócitos T/citologia , Linfócitos T/imunologia , Linfócitos T/metabolismo
19.
Int J Mol Sci ; 21(9)2020 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-32397174

RESUMO

On 7 January 2020, researchers isolated and sequenced in China from patients with severe pneumonitis a novel coronavirus, then called SARS-CoV-2, which rapidly spread worldwide, becoming a global health emergency. Typical manifestations consist of flu-like symptoms such as fever, cough, fatigue, and dyspnea. However, in about 20% of patients, the infection progresses to severe interstitial pneumonia and can induce an uncontrolled host-immune response, leading to a life-threatening condition called cytokine release syndrome (CRS). CRS represents an emergency scenario of a frequent challenge, which is the complex and interwoven link between infections and autoimmunity. Indeed, treatment of CRS involves the use of both antivirals to control the underlying infection and immunosuppressive agents to dampen the aberrant pro-inflammatory response of the host. Several trials, evaluating the safety and effectiveness of immunosuppressants commonly used in rheumatic diseases, are ongoing in patients with COVID-19 and CRS, some of which are achieving promising results. However, such a use should follow a multidisciplinary approach, be accompanied by close monitoring, be tailored to patient's clinical and serological features, and be initiated at the right time to reach the best results. Autoimmune patients receiving immunosuppressants could be prone to SARS-CoV-2 infections; however, suspension of the ongoing therapy is contraindicated to avoid disease flares and a consequent increase in the infection risk.


Assuntos
Antivirais/uso terapêutico , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/imunologia , Síndrome da Liberação de Citocina/patologia , Pneumonia Viral/tratamento farmacológico , Pneumonia Viral/imunologia , Doenças Autoimunes/complicações , Doenças Autoimunes/tratamento farmacológico , Doenças Autoimunes/patologia , Betacoronavirus/fisiologia , Ensaios Clínicos como Assunto , Infecções por Coronavirus/complicações , Infecções por Coronavirus/patologia , Síndrome da Liberação de Citocina/tratamento farmacológico , Síndrome da Liberação de Citocina/imunologia , Humanos , Imunossupressores/uso terapêutico , Pandemias , Pneumonia Viral/complicações , Pneumonia Viral/patologia
20.
Eur J Paediatr Neurol ; 26: 89-91, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32340854

RESUMO

Autoimmune glial fibrillary acidic protein (GFAP) astrocytopathy is a rare recently defined antibody-mediated encephalitis. Meningo-encephalomyelitis presentation is frequent with lymphocytic pleiocytosis in the cerebro-spinal fluid and brain MRI classically demonstrates in 50% of cases, a linear perivascular enhancement extending radially from the ventricles. Here, we describe 2 cases of pediatric autoimmune GFAP astrocytopathy with limbic encephalitis presentation and peculiar MRI characteristics: one with normal MRI and the second suggestive of Mild Encephalitis/Encephalopathy with reversible splenial lesion syndrome (MERS). These two cases illustrate that anti-GFAP antibodies should be sought in children presenting limbic encephalitis with a normal and/or MERS suggestive MRI, as treatment strategies may differ.


Assuntos
Astrócitos/patologia , Doenças Autoimunes/imunologia , Proteína Glial Fibrilar Ácida/imunologia , Encefalite Límbica/imunologia , Adolescente , Astrócitos/imunologia , Autoanticorpos/imunologia , Autoantígenos/imunologia , Doenças Autoimunes/patologia , Criança , Feminino , Humanos , Encefalite Límbica/patologia , Imagem por Ressonância Magnética , Masculino
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