RESUMEN
BACKGROUND: Oral lesions of immune-mediated and autoimmune diseases have been well-documented, but studies from Brazil are limited. The varied spectrum of oral lesions within this demographic group poses challenges to clinicians, particularly when they occur in isolation. This study aimed to evaluate the occurrence, clinical characteristics, and management of patients with oral lesions of immune-mediated and autoimmune diseases at a single center in Brazil. METHODS: A retrospective cross-sectional study was conducted from 2010 to 2022. Clinicodemographic data, histopathological features, and treatment modalities were analyzed descriptively and analytically. RESULTS: Of the 3,790 oral and maxillofacial lesions diagnosed, 160 (4.2%) were confirmed as immune-mediated or autoimmune diseases. The population surveyed predominantly consisted of women (73.7%), with a mean age of 60.2 years. Oral lichen planus (51.3%), mucous membrane pemphigoid (MMP) (23.7%), and pemphigus vulgaris (PV) (19.4%) were the most prevalent lesions. The buccal mucosa (59.4%) was predominantly affected, with pain reported in 46.2% of cases, notably in individuals with PV and MMP. The average time to disease stabilization post-local and/or systemic corticosteroid therapy was 15.8 months for systemic lupus erythematosus, 8.7 months for MMP, and 6.5 months for PV. CONCLUSION: Although oral lesions related to immune-mediated and autoimmune diseases are uncommon, their diverse clinicopathological aspects require multidisciplinary management.
Asunto(s)
Enfermedades Autoinmunes , Enfermedades de la Boca , Humanos , Femenino , Estudios Retrospectivos , Persona de Mediana Edad , Masculino , Estudios Transversales , Enfermedades Autoinmunes/patología , Brasil/epidemiología , Enfermedades de la Boca/patología , Anciano , Adulto , Adulto Joven , Anciano de 80 o más Años , AdolescenteRESUMEN
OBJECTIVES: Leprosy is a chronic granulomatous disease caused by Mycobacterium leprae. Less frequently, there is involvement of the musculoskeletal system, and occurrence of systemic manifestation with non-specific symptoms such as fever, fatigue and myalgia. Therefore, leprosy can often mimic autoimmune diseases such as arthritis, vasculitis, or collagenosis and be mis-diagnosed. METHODS: This study describes a series of cases of leprosy mimicking autoimmune diseases in patients treated in the Rheumatology Department of our centre in the period 2019 to 2023. All patients were investigated regarding leprosy criteria and had clinical evaluation, serum markers, and histopathological analyses recorded. The diagnosis of leprosy was confirmed using skin biopsy followed by testing for acid-fast bacillus (AFB) or smear microscopy. RESULTS: Six patients who were initially investigated for autoimmune diseases were identified as diagnosed as leprosy cases, fulfilling both clinical and histopathologic criteria, two of whom presented with symptoms of polyarthritis with an inflammatory characteristic, two diffuse erythematous-violaceous lesions, three recurrent fever, three arthralgia, and one Raynaud's phenomenon, which are all characteristics present most frequently in rheumatologic diseases. CONCLUSIONS: We must consider the bacillary infection as a differential diagnosis of autoimmune diseases. Histopathological analysis is an important tool and the gold standard for diagnostic confirmation.
Asunto(s)
Artritis , Enfermedades Autoinmunes , Lepra , Humanos , Lepra/diagnóstico , Lepra/tratamiento farmacológico , Lepra/microbiología , Mycobacterium leprae , Piel/patología , Enfermedades Autoinmunes/diagnóstico , Enfermedades Autoinmunes/patologíaRESUMEN
Cutaneous lupus erythematosus is an autoimmune disease of varied clinical expression, which may present as an exclusively cutaneous disease or be one of the multiple manifestations of systemic lupus erythematosus. Its classification includes acute, subacute, intermittent, chronic and bullous subtypes, which are usually identified based on clinical features and histopathological and laboratory findings. Other non-specific cutaneous manifestations may be associated with systemic lupus erythematosus and are usually related to disease activity. Environmental, genetic and immunological factors play a role in the pathogenesis of skin lesions in lupus erythematosus. Recently, considerable progress has been made in elucidating the mechanisms involved in their development, which allows for foreseeing future targets for more effective treatments. This review proposes to discuss the main etiopathogenic, clinical, diagnostic and therapeutic aspects of cutaneous lupus erythematosus, aiming to update internists and specialists from different areas.
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Enfermedades Autoinmunes , Lupus Eritematoso Cutáneo , Lupus Eritematoso Discoide , Lupus Eritematoso Sistémico , Humanos , Lupus Eritematoso Discoide/patología , Lupus Eritematoso Cutáneo/diagnóstico , Lupus Eritematoso Cutáneo/etiología , Lupus Eritematoso Cutáneo/terapia , Lupus Eritematoso Sistémico/complicaciones , Enfermedades Autoinmunes/patología , Piel/patologíaRESUMEN
A 7-year-old girl presented with a 2-year history of recurrent blisters on the skin and oral mucosa. The patient was otherwise healthy, and her family history was unremarkable for any dermatologic or other medical disease. Examination revealed multiple tense vesicles, milia, and atrophic scars present over the extensor surface of the extremities and erosions on the oral mucosa (Figure 1). A skin biopsy established a pauci-inflammatory subepidermal blister (Figure 2a). Direct immunofluorescence (DIF) evidenced the linear deposition of immunoglobulin G (IgG), immunoglobulin M (IgM), and κ and λ chains at the dermal-epithelial junction (DEJ). Indirect immunofluorescence (IIF), using the salt-split technique, established anti-epithelial antibodies on the dermal side (Figure 2b). An enzyme-linked immunosorbent assay (ELISA) was positive for Collagen Type VII (COL7) antibodies. A diagnosis of epidermolysis bullosa acquisita (EBA) was made, and treatment with azathioprine and deflazacort was administered for 8 months with progressive lessening of her symptomatology and complete clinical response at 2-year follow-up. (SKINmed. 2022;20:460-462).
Asunto(s)
Enfermedades Autoinmunes , Epidermólisis Ampollosa Adquirida , Femenino , Humanos , Niño , Vesícula , Piel/patología , Enfermedades Autoinmunes/patología , Inmunoglobulina GRESUMEN
Abstract Autoimmune gastritis is an underdiagnosed disease in the pediatric population due to the absence of specific signs and symptoms and late clinical manifestations. Iron deficiency anemia has recently been identified as an early hematological manifestation, allowing an early diagnostic approach. We present the case of a Colombian teenager, with no history of autoimmunity, with refractory iron deficiency. He underwent extension studies; biopsies and serology compatible with autoimmune gastritis were documented, requiring parenteral iron in its evolution. This pathology is underdiagnosed in our context since early diagnosis requires a high index of suspicion to prevent associated complications.
Resumen La gastritis autoinmune es una enfermedad subdiagnosticada en la población pediátrica. Lo anterior se debe a la ausencia de signos y síntomas específicos y manifestaciones clínicas tardías. Recientemente se ha identificado la anemia ferropénica como una manifestación hematológica precoz, lo que permite un enfoque diagnóstico temprano. Se presenta el caso de un adolescente colombiano, sin antecedentes de autoinmunidad, con ferropenia refractaria, en el que se realizaron estudios de extensión y se documentaron biopsias y serología compatible con gastritis autoinmune, con requerimiento de hierro parenteral en su evolución. Esta patología es subdiagnosticada en nuestro medio, ya que el diagnóstico temprano requiere un alto índice de sospecha, lo que permite la prevención de las complicaciones asociadas.
Asunto(s)
Humanos , Masculino , Adolescente , Enfermedades Autoinmunes/diagnóstico , Anemia Ferropénica/diagnóstico , Gastritis/diagnóstico , Enfermedades Autoinmunes/patología , Biopsia , Endoscopía del Sistema Digestivo , Diagnóstico Precoz , Mucosa Gástrica/patología , Gastritis/patologíaRESUMEN
Mitochondrial dysfunction is a plausible cause of muscle fibre damage in a number of myopathies including immune-mediated necrotising myopathy. However, histopathological evidence of mitochondrial dysfunction is not often described in immune-mediated necrotising myopathy and, when present, it is often attributed to patient age. The purpose of this study was to describe features of mitochondrial dysfunction on muscle biopsy in anti-3hydroxy-3-methylglutaryl-CoA reductase immune-mediated necrotising myopathy and explore whether these features are age-related. In this observational case control study, a statistically significant increase in the number of muscle fibres with increased lipid content (pâ¯=â¯0.004) and cytochrome c oxidase-negative/succinate dehydrogenase-positive fibres (pâ¯=â¯0.037) in anti-3hydroxy-3-methylglutaryl-coenzyme immune-mediated necrotising myopathy was found compared to age-matched controls. Therefore, histopathological features of mitochondrial dysfunction are more frequent in anti-3hydroxy-3-methylglutaryl-coenzyme immune-mediated necrotising myopathy than aged-matched controls and therefore, may be contributing to the pathogenesis.
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Enfermedades Autoinmunes , Inhibidores de Hidroximetilglutaril-CoA Reductasas , Enfermedades Musculares , Miositis , Autoanticuerpos , Enfermedades Autoinmunes/patología , Estudios de Casos y Controles , Coenzimas , Humanos , Hidroximetilglutaril-CoA Reductasas , Mitocondrias/patología , Músculo Esquelético/patología , Enfermedades Musculares/patología , Miositis/patología , Necrosis/patologíaRESUMEN
Immunoglobulin G4 (IgG4-RD) -related disease is a regional or systemic fibroinflammatory disease of unknown etiology. It has a characteristic histopathological appearance of dense lymphoplasmacytic infiltrates with abundant IgG4 positive plasma cells, storiform fibrosis and obliterative phlebitis with the appearance of inflammatory swelling or swollen lesions. This entity frequently affects the pancreas, salivary glands, and lymph nodes, but it can compromise almost any structure in the human anatomy. This new disease entity includes a wide variety of diseases such as Mikulicz disease, autoimmune pancreatitis, Riedel's thyroiditis, interstitial nephritis, and retroperitoneal fibrosis. Glucocorticoid therapy can resolve clinical and pathologic abnormalities and impaired organ function. IgG4-RD was internationally recognized in 2011, and new evidence has accumulated on its pathogenesis, clinical characteristics, and treatment. However, much is still unknown about the behavior of IgG4 in vivo, the participation of this molecule in disease, and whether its role in IgG4-related disease is primary or secondary. The text below is based on a brief review of the most recent literature on this entity in relation to a clinical case.
Asunto(s)
Humanos , Masculino , Anciano , Enfermedades Autoinmunes/inmunología , Enfermedad Relacionada con Inmunoglobulina G4/diagnóstico , Enfermedad Relacionada con Inmunoglobulina G4/terapia , Enfermedades Autoinmunes/patología , Cuidados Posteriores , Enfermedad Relacionada con Inmunoglobulina G4 , Enfermedad Relacionada con Inmunoglobulina G4/fisiopatología , Enfermedad Relacionada con Inmunoglobulina G4/epidemiología , Pancreatitis Autoinmune , Enfermedad de MikuliczRESUMEN
Epigenetic mechanisms, such as DNA methylation, histone modifications, and non-coding RNAs are known regulators of gene expression and genomic stability in cell growth, development, and differentiation. Because epigenetic mechanisms can regulate several immune system elements, epigenetic alterations have been found in several autoimmune diseases. The purpose of this review is to discuss the epigenetic modifications, mainly DNA methylation, involved in autoimmune diseases in which T cells play a significant role. For example, Rheumatoid Arthritis and Systemic Lupus Erythematosus display differential gene methylation, mostly hypomethylated 5'-C-phosphate-G-3' (CpG) sites that may associate with disease activity. However, a clear association between DNA methylation, gene expression, and disease pathogenesis must be demonstrated. A better understanding of the impact of epigenetic modifications on the onset of autoimmunity will contribute to the design of novel therapeutic approaches for these diseases.
Asunto(s)
Enfermedades Autoinmunes/patología , Metilación de ADN , Epigénesis Genética , Predisposición Genética a la Enfermedad , Código de Histonas , Animales , Enfermedades Autoinmunes/etiología , HumanosRESUMEN
Systemic autoimmune diseases are complex clinical conditions that arise in genetically predisposed individuals as a result of the interplay between their immune system and their environment. In this perspective, we briefly discuss our current understanding of the pathogenesis of autoimmunity and indicate four research avenues whose exploration will bring us closer to resolving fundamental questions that remain unanswered in this enigmatic field.
Asunto(s)
Enfermedades Autoinmunes , Autoinmunidad , Predisposición Genética a la Enfermedad , Enfermedades Autoinmunes/genética , Enfermedades Autoinmunes/inmunología , Enfermedades Autoinmunes/patología , Autoinmunidad/genética , HumanosRESUMEN
INTRODUCTION AND OBJECTIVES: It has been proposed that non-invasive methods may replace liver biopsy for the diagnosis of tissue damage in patients with autoimmune liver disease (ALD). The aim of this study was to determine diagnostic performance and degree of concordance between the APRI index and liver biopsy for diagnosing cirrhosis in these patients. MATERIAL AND METHODS: In a cohort of patients with ALD, the value of the APRI index and liver biopsy results were determined according to the METAVIR score. The AUC and the degree of concordance between an APRI value >2 and a METAVIR score of F4 were evaluated as markers of liver cirrhosis, through a kappa statistic. RESULTS: In total, 70 patients (age 51 ± 13 years) were included. The most common autoimmune liver diseases were primary biliary cirrhosis (PBC) (40%), autoimmune hepatitis (AIH) (24.3%) and AIH-PBC overlap syndrome (32.9%). Cirrhosis was confirmed by biopsy in 16 patients (22.9%). 15 patients (21.4%) had an APRI index >2 (Cirrhosis) and only six met both criteria. The AUC of the APRI was 0.77 (95% CI 0.65-0.88). The degree of concordance between the tests was low for an APRI cut-off point >2 (kappa 0.213; 95% CI 0.094-0.332), as well as for cut-off points >1.5, >1 and >0.5 (kappa 0.213, 0.255, 0.257, respectively) CONCLUSION: Our results suggest that there is little concordance between APRI and liver biopsy for the diagnosis of cirrhosis in patients with ALD. It should therefore not be used as a single diagnostic method to determine cirrhosis.
Asunto(s)
Aspartato Aminotransferasas/sangre , Enfermedades Autoinmunes/patología , Cirrosis Hepática/sangre , Cirrosis Hepática/patología , Hepatopatías/sangre , Hepatopatías/inmunología , Hepatopatías/patología , Hígado/patología , Adulto , Biomarcadores/sangre , Biopsia , Femenino , Humanos , Masculino , Persona de Mediana Edad , Recuento de Plaquetas , Estudios RetrospectivosRESUMEN
Experimental autoimmune orchitis (EAO) is a useful model to study organ-specific autoimmunity and chronic testicular inflammation. This model reflects testicular pathological changes reported in immunological infertility in men. Progression of EAO in rodents is associated with a significantly increased percentage of testicular endothelial cells and interstitial testicular blood vessels, indicating an ongoing angiogenic process. Vascular endothelial growth factor A (VEGFA), the main regulator of physiological and pathological angiogenesis, can stimulate endothelial cell proliferation, chemotaxis and vascular permeability. The aim of this study was to explore the role of VEGFA in the pathogenesis of testicular inflammation. Our results found VEGFA expression in Leydig cells, endothelial cells and macrophages in testis of rats with autoimmune orchitis. VEGFA level was significantly higher in testicular fluid and serum of rats at the end of the immunization period, preceding testicular damage. VEGF receptor (VEGFR) 1 is expressed mainly in testicular endothelial cells, whereas VEGFR2 was detected in germ cells and vascular smooth muscle cells. Both receptors were expressed in testicular interstitial cells. VEGFR2 increased after the immunization period in the testicular interstitium and VEGFR1 was downregulated in EAO testis. In-vivo-specific VEGFA inhibition by Bevacizumab prevented the increase in blood vessel number and reduced EAO incidence and severity. Our results unveil relevance of VEGFA-VEGFR axis during orchitis development, suggesting that VEGFA might be an early marker of testicular inflammation and Bevacizumab a therapeutic tool for treatment of testicular inflammation associated with subfertility and infertility.
Asunto(s)
Enfermedades Autoinmunes/patología , Neovascularización Patológica , Testículo/irrigación sanguínea , Testículo/metabolismo , Factor A de Crecimiento Endotelial Vascular/metabolismo , Inhibidores de la Angiogénesis/farmacología , Animales , Enfermedades Autoinmunes/inmunología , Enfermedades Autoinmunes/metabolismo , Enfermedades Autoinmunes/prevención & control , Bevacizumab/farmacología , Modelos Animales de Enfermedad , Células Endoteliales/metabolismo , Células Endoteliales/patología , Células Intersticiales del Testículo/metabolismo , Células Intersticiales del Testículo/patología , Macrófagos/metabolismo , Macrófagos/patología , Masculino , Miocitos del Músculo Liso/metabolismo , Miocitos del Músculo Liso/patología , Orquitis/inmunología , Orquitis/metabolismo , Orquitis/prevención & control , Codorniz/embriología , Ratas Wistar , Transducción de Señal , Testículo/efectos de los fármacos , Receptor 1 de Factores de Crecimiento Endotelial Vascular/metabolismo , Receptor 2 de Factores de Crecimiento Endotelial Vascular/metabolismoRESUMEN
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)
Asunto(s)
Humanos , Autoanticuerpos/metabolismo , Enfermedades Autoinmunes/patología , Síndromes Paraneoplásicos del Sistema Nervioso/patología , Encefalitis Límbica/patología , Trastornos Psicóticos/diagnóstico , Trastornos Psicóticos/etiología , Enfermedades Autoinmunes/diagnóstico , Enfermedades Autoinmunes/etiología , Enfermedades Autoinmunes/terapia , Literatura de Revisión como Asunto , Síndromes Paraneoplásicos del Sistema Nervioso/diagnóstico , Síndromes Paraneoplásicos del Sistema Nervioso/etiología , Síndromes Paraneoplásicos del Sistema Nervioso/terapia , Encefalitis Límbica/diagnóstico , Encefalitis Límbica/etiología , Encefalitis Límbica/historia , Encefalitis Límbica/terapia , Epilepsia/diagnóstico , Epilepsia/etiologíaRESUMEN
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.
Asunto(s)
Apoptosis/fisiología , Mitocondrias/metabolismo , Músculo Esquelético/metabolismo , Mioblastos/patología , Miositis/patología , Adenosina Trifosfato/análisis , Anciano , Autoanticuerpos/inmunología , Enfermedades Autoinmunes/patología , Células Cultivadas , Estrés del Retículo Endoplásmico/fisiología , Femenino , Humanos , Masculino , Potencial de la Membrana Mitocondrial/fisiología , Persona de Mediana Edad , Fosforilación Oxidativa , Estrés Oxidativo/fisiología , Especies Reactivas de Oxígeno/metabolismoRESUMEN
Thyroid cancer (TC) is the most prevalent malignant neoplasm that affects the endocrine system. Hashimoto's thyroiditis (HT), also known as chronic lymphocytic thyroiditis, is the most common autoimmune thyroid disease (AITD) that, together with Graves' disease (GD), represent the main autoimmune diseases that affect the thyroid gland. Some studies suggest a greater risk of AITD and the development of TC, while others, investigate its relationship with TC progression and patient prognosis. In this review, we have analyzed published data on the molecular aspects related to the association between AITD and TC, addressing their influence on TC progression, diagnosis, and prognosis of the patients. MEDLINE database (PubMed) platform was used as a search engine and the original articles related to the topic were selected using the keywords combination "thyroid cancer and Hashimoto thyroiditis" or "thyroid carcinoma and thyroid autoimmune disease". After the selection, we categorized the main findings of the papers into four topics: antitumor immunity, tumor progression, diagnosis, and prognosis. Although most of the studies have pointed out the presence of AITD as a factor that increases the risk of TC, few molecular mechanisms to support this conclusion have been described. Additionally, little information is available to explain, pathophysiologically, the effects of autoimmunity in TC diagnosis, progression, and prognosis.
Asunto(s)
Enfermedades Autoinmunes/genética , Enfermedad de Graves/inmunología , Enfermedad de Hashimoto/inmunología , Neoplasias de la Tiroides/patología , Enfermedades Autoinmunes/inmunología , Enfermedades Autoinmunes/patología , Predisposición Genética a la Enfermedad/genética , Enfermedad de Graves/patología , Enfermedad de Hashimoto/patología , Humanos , Glándula Tiroides/inmunología , Glándula Tiroides/patología , Neoplasias de la Tiroides/inmunologíaRESUMEN
Inflammasomes are cytosolic multiprotein complexes that sense microbial infections or host cell damage, triggering cytokine production and a proinflammatory form of cell death, called pyroptosis. Whereas pyroptosis and cytokine production may often promote host resistance to infections, uncontrolled inflammasome activation leads to autoinflammatory diseases in humans. Among the multiple inflammasomes described, the neuronal apoptosis inhibitory protein/nucleotide-binding domain leucine-rich repeat-containing protein family caspase activation and recruitment domain-containing protein 4 (NLRC4) inflammasome emerged as a critical component for the restriction of bacterial infections. Accordingly, our understanding of this inflammasome advanced remarkably over the last 10 yr, expanding our knowledge about ligand-receptor interaction; cryo-EM structure; and downstream effectors and substrates, such as gasdermin-D, caspase-1, caspase-8, and caspase-7. In this review, we discuss recent advances on the biology of the NLRC4 inflammasome, in terms of structure and activation mechanisms, importance in bacterial and nonbacterial diseases, and the identification of NLRC4 gain-of-function mutations leading to NLRC4-associated autoinflammatory diseases in humans.
Asunto(s)
Enfermedades Autoinmunes/inmunología , Infecciones Bacterianas/inmunología , Proteínas Adaptadoras de Señalización CARD/inmunología , Proteínas de Unión al Calcio/inmunología , Inflamasomas/inmunología , Animales , Enfermedades Autoinmunes/patología , Infecciones Bacterianas/patología , Caspasa 1/inmunología , Caspasa 7 , Caspasa 8/inmunología , Humanos , Péptidos y Proteínas de Señalización Intracelular/inmunología , Proteínas de Unión a Fosfato/inmunologíaRESUMEN
Immune-mediated necrotizing myopathy with antibodies against 3-hydroxy-3-methylglutaryl-coenzyme A reductase is a subgroup of idiopathic inflammatory myopathies mainly described in adults and requiring long term immunomodulatory therapy for remission. Pediatric patients have been reported as small series or sporadic cases. We report an eight-year-old girl with anti-3-hydroxy-3-methylglutaryl-coenzyme A reductase myopathy, presenting with subacute proximal limb weakness, high creatine kinase and a muscle biopsy displaying necrotizing pattern, initially diagnosed as limb-girdle muscular dystrophy, but subsequently negative genetic testing. A noteworthy spontaneous improvement in her weakness suggested the possibility of an acquired autoimmune myopathy, confirmed by positive testing of anti-HMGCR antibodies titers. After four years of follow-up, she maintains normal strength with high levels of anti-3-hydroxy-3-methylglutaryl-coenzyme A reductase antibody. This patient shows that spontaneous fluctuations and spontaneous long-lasting symptomatic remission can occur in patients with anti-3-hydroxy-3-methylglutaryl-coenzyme A reductase myopathy. Some patients could present a wane and wax clinical course, an important aspect when assessing response to therapy.
Asunto(s)
Enfermedades Autoinmunes , Hidroximetilglutaril-CoA Reductasas/inmunología , Miositis , Autoanticuerpos , Enfermedades Autoinmunes/sangre , Enfermedades Autoinmunes/inmunología , Enfermedades Autoinmunes/patología , Enfermedades Autoinmunes/fisiopatología , Niño , Femenino , Humanos , Miositis/sangre , Miositis/inmunología , Miositis/patología , Miositis/fisiopatología , Remisión EspontáneaRESUMEN
Aging elicits quantitative and qualitative changes in different immune components, leading to disruption of tolerogenic circuits and development of autoimmune disorders. Galectin-1 (Gal1), an endogenous glycan-binding protein, has emerged as a regulator of immune cell homeostasis by shaping the fate of myeloid and lymphoid cells. Here, we demonstrate that aged Gal1-null mutant (Lgals1-/- ) mice develop a spontaneous inflammatory process in salivary glands that resembles Sjögren's syndrome. This spontaneous autoimmune phenotype was recapitulated in mice lacking ß1,6N-acetylglucosaminyltransferase V (Mgat5), an enzyme responsible for generating ß1,6-branched complex N-glycans, which serve as a major ligand for this lectin. Lack of Gal1 resulted in CD11c+ dendritic cells (DCs) with higher immunogenic potential, lower frequency of Foxp3+ regulatory T cells (Tregs), and increased number of CD8+ T cells with greater effector capacity. Supporting its tolerogenic activity, Gal1 expression decreased with age in autoimmunity-prone nonobese diabetic (NOD) mice. Treatment with recombinant Gal1 restored tolerogenic mechanisms and reduced salivary gland inflammation. Accordingly, labial biopsies from primary Sjögren's syndrome patients showed reduced Gal1 expression concomitant with higher number of infiltrating CD8+ T cells. Thus, endogenous Gal1 serves as a homeostatic rheostat that safeguards immune tolerance and prevents age-dependent development of spontaneous autoimmunity.
Asunto(s)
Enfermedades Autoinmunes/patología , Galectina 1/fisiología , Tolerancia Inmunológica/inmunología , Glándulas Salivales/patología , Sialadenitis/patología , Síndrome de Sjögren/patología , Linfocitos T Reguladores/inmunología , Adulto , Factores de Edad , Animales , Enfermedades Autoinmunes/inmunología , Enfermedades Autoinmunes/metabolismo , Estudios de Casos y Controles , Células Dendríticas/inmunología , Femenino , Glicosilación , Humanos , Masculino , Ratones , Ratones Endogámicos BALB C , Ratones Endogámicos C57BL , Ratones Endogámicos NOD , Ratones Noqueados , Persona de Mediana Edad , N-Acetilglucosaminiltransferasas/fisiología , Polisacáridos/metabolismo , Glándulas Salivales/inmunología , Glándulas Salivales/metabolismo , Sialadenitis/inmunología , Sialadenitis/metabolismo , Síndrome de Sjögren/inmunología , Síndrome de Sjögren/metabolismoRESUMEN
Abstract Hidradenitis suppurativa is a chronic inflammatory skin disease, which affects 1% of the population, being more common in young, obese and smokers, and mainly affects armpits and groin, with formation of pustules, nodules, abscesses, scars and fistulas. Recently, its association with other autoimmune diseases such as psoriasis, psoriatic arthritis, pyoderma gangrenosum, pyogenic arthritis and ulcerative colitis have been reported. These associated forms are usually resistant to standard treatment, with immunobiologicals as promising therapy. The case of a rare form of association is reported, with only one case previously described in the literature: psoriasis arthritis, pyoderma gangrenosum, acne and hidradenitis suppurativa.
Asunto(s)
Humanos , Femenino , Adulto Joven , Artritis Psoriásica/patología , Piodermia Gangrenosa/patología , Hidradenitis Supurativa/patología , Acné Vulgar/patología , Enfermedades Autoinmunes/patología , SíndromeRESUMEN
Hidradenitis suppurativa is a chronic inflammatory skin disease, which affects 1% of the population, being more common in young, obese and smokers, and mainly affects armpits and groin, with formation of pustules, nodules, abscesses, scars and fistulas. Recently, its association with other autoimmune diseases such as psoriasis, psoriatic arthritis, pyoderma gangrenosum, pyogenic arthritis and ulcerative colitis have been reported. These associated forms are usually resistant to standard treatment, with immunobiologicals as promising therapy. The case of a rare form of association is reported, with only one case previously described in the literature: psoriasis arthritis, pyoderma gangrenosum, acne and hidradenitis suppurativa.
Asunto(s)
Acné Vulgar/patología , Artritis Psoriásica/patología , Hidradenitis Supurativa/patología , Piodermia Gangrenosa/patología , Enfermedades Autoinmunes/patología , Femenino , Humanos , Síndrome , Adulto JovenRESUMEN
The aim of this work was to study effects of ketotifen fumarate (KF) on prevention of tissue damage in testes of rats with experimental autoimmune orchitis (EAO) and on the contralateral testis in a model of prolonged testicular cord torsion (TCT). Rats with EAO or TCT were injected intraperitoneally once daily with KF or saline solution (vehicle group). Incidence and severity of testicular damage were evaluated by histopathology using an EAO score or a Johnsen score. Mast cells (MC) were identified by histochemistry and quantified. In EAO model, KF significantly reduced severity of histopathological testicular damage compared to rats in the vehicle group. KF also reduced the number of testicular MC compared to vehicle group. Similarly, in TCT model, multifocal damage of the contralateral testis was observed 30 days after testicular torsion characterized by sloughing of the germinal epithelium, seminiferous tubule atrophy, and interstitial edema. Focal signs of inflammation and fibrosis of seminiferous tubular walls were also observed. In contrast, sections of contralateral testis of rats injected with KF and killed 30 days after surgery showed normal histological features. A significant decrease in the number of MC was observed in rats treated with KF compared to untreated animals. In conclusion, we demonstrated that treatment with KF reduced testicular inflammatory process and MC infiltrates in both EAO and TCT models. The results suggest a promising treatment for infertile male patients with testicular pathologies associated with inflammation and germ cell loss.