RESUMEN
Interleukin (IL) 17 is a proinflammatory cytokine belonging to a structurally related group of cytokines known as the IL-17 family. It has been profoundly studied for its contribution to the pathology of autoimmune diseases. However, it also plays an important role in homeostasis and the defense against extracellular bacteria and fungi. IL-17 is important for epithelial barriers, including the skin, where some of its cellular targets reside. Most of the research work on IL-17 has focused on its effects in the skin within the context of autoimmune diseases or sterile inflammation, despite also having impact on other skin conditions. In recent years, studies on the role of IL-17 in the defense against skin pathogens and in the maintenance of skin homeostasis mediated by the microbiota have grown in importance. Here we review and discuss the cumulative evidence regarding the main contribution of IL-17 in the maintenance of skin integrity as well as its protective or pathogenic effects during some skin infections.
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Interleucina-17 , Piel , Animales , Humanos , Homeostasis , Interleucina-17/inmunología , Interleucina-17/metabolismo , Piel/inmunología , Piel/microbiología , Piel/patología , Enfermedades Cutáneas Infecciosas/inmunología , Enfermedades Cutáneas Infecciosas/microbiología , Enfermedades Autoinmunes/inmunologíaRESUMEN
Autoimmune diseases comprise a spectrum of disorders characterized by the dysregulation of immune tolerance, resulting in tissue or organ damage and inflammation. Their prevalence has been on the rise, significantly impacting patients' quality of life and escalating healthcare costs. Consequently, the prediction of autoimmune diseases has recently garnered substantial interest among researchers. Despite their wide heterogeneity, many autoimmune diseases exhibit a consistent pattern of paraclinical findings that hold predictive value. From serum biomarkers to various machine learning approaches, the array of available methods has been continuously expanding. The emergence of artificial intelligence (AI) presents an exciting new range of possibilities, with notable advancements already underway. The ultimate objective should revolve around disease prevention across all levels. This review provides a comprehensive summary of the most recent data pertaining to the prediction of diverse autoimmune diseases and encompasses both traditional biomarkers and the latest innovations in AI.
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Inteligencia Artificial , Enfermedades Autoinmunes , Biomarcadores , Humanos , Biomarcadores/sangre , Enfermedades Autoinmunes/diagnóstico , Enfermedades Autoinmunes/sangre , Enfermedades Autoinmunes/inmunología , Aprendizaje Automático , PronósticoRESUMEN
INTRODUCTION: Arthralgias are prevalent in systemic autoimmune rheumatic diseases (SARD), emphasizing the need for early recognition. This study aimed to estimate SARD frequency and compare clinical, laboratory, and imaging findings among SARD, non-inflammatory arthralgia (NIA), and RA in patients with hand arthralgias. METHODS: A prospective evaluation program included individuals aged ≥18 with hand arthralgias. Baseline assessments covered clinical, laboratory, ultrasound, and radiography. Follow-up diagnoses categorized patients into SARD, NIA, and RA groups. Comparison between groups was performed using parametric and non-parametric tests. Two multivariate logistic regression analyzes were performed using the final diagnosis of SARD as the dependent variable (NIA and RA). ROC curves were calculated in those variables that presented an independent association in the multivariate analysis. RESULTS: Among 1053 patients, 9.6% were SARD (SLE 47%). Comparing SARD with NIA revealed higher CRP levels, power Doppler, less rhizarthrosis in ultrasound, and more ANA positivity in SARD patients. Distinct differences were observed between SARD and RA patients in terms of pain levels, swollen joints, metacarpophalangeal involvement and morning symptoms. Diagnostic markers demonstrated specific sensitivities and specificities: ANA for SARD versus NIA (82%, 34%), US not finding rhizarthrosis for SARD versus NIA (66%, 85%), CRP (cut-off >2.5 mg/L) sensitivity 52%, specificity 60%, AUC 0.62, RA antibodies (RF, 11 IU/mL) sensitivity 76%, specificity 74%, AUC 0.8, ACPA (1.25) sensitivity 50%, specificity 98%, AUC 0.7, ANA+ sensitivity 95%, specificity 32%, AUC 0.7, and US absence of synovitis sensitivity 82%, specificity 34%, AUC 0.75. CONCLUSION: This study highlights distinct clinical, laboratory, and imaging features differentiating SARD-related hand arthralgia from non-SARD hand arthralgia and RA.
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Artralgia , Enfermedades Autoinmunes , Articulaciones de la Mano , Valor Predictivo de las Pruebas , Humanos , Masculino , Femenino , Persona de Mediana Edad , Estudios Prospectivos , Artralgia/diagnóstico , Adulto , Articulaciones de la Mano/diagnóstico por imagen , Enfermedades Autoinmunes/diagnóstico , Enfermedades Autoinmunes/epidemiología , Enfermedades Autoinmunes/inmunología , Artritis Reumatoide/diagnóstico , Artritis Reumatoide/epidemiología , Anciano , Diagnóstico Diferencial , Biomarcadores/sangre , PrevalenciaRESUMEN
OBJECTIVE: To assess the prevalence of systemic and organ-specific autoimmunity among individuals with human inborn errors of immunity (IEI). METHODS: Retrospective study. We recorded demographic variables, type of immunodeficiency, and systemic and organ specific autoimmunity. RESULTS: We included 48 patients (54.1% men) with mean age of 32.1 years. The most common IEIs included combined immunodeficiency with syndromic features (31.2%) and predominantly antibody deficiency (20.1%). We observed autoimmunity in 15 patients (31.2%): 12 organ-specific autoimmunity and 5 systemic autoimmunity, not mutually exclusive groups. Organ-specific autoimmunity preceded the onset of IEI in 5 patients, was concurrent in one patient, and developed after the diagnosis of IEI in 6 cases. From the systemic autoimmunity group, we observed polyarteritis nodosa (nâ¯=â¯2), antiphospholipid syndrome (APS) (nâ¯=â¯2), and overlap of limited systemic sclerosis/APS/Sjögren's syndrome (nâ¯=â¯1), and in all cases, this occurred after the IEI diagnosis. CONCLUSION: Our findings confirm the coexistence of autoimmunity and IEI. This overlap may be attributed to B and T cell disorders, as well as potential alterations in the microbiota in these patients.
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Enfermedades Autoinmunes , Autoinmunidad , Humanos , Masculino , Estudios Retrospectivos , Femenino , Adulto , Adolescente , Adulto Joven , Persona de Mediana Edad , Niño , Enfermedades Autoinmunes/inmunología , Enfermedades Autoinmunes/complicaciones , Preescolar , LactanteRESUMEN
Innate immune system activation is crucial in the inflammatory response, but uncontrolled activation can lead to autoimmune diseases. Cellular exhaustion and senescence are two processes that contribute to innate immune tolerance breakdown. Exhausted immune cells are unable to respond adequately to specific antigens or stimuli, while senescent cells have impaired DNA replication and metabolic changes. These processes can impair immune system function and disrupt homeostasis, leading to the emergence of autoimmunity. However, the influence of innate immune exhaustion and senescence on autoimmune disorders is not well understood. This review aims to describe the current findings on the role of innate immune exhaustion and senescence in autoimmunity, focusing on the cellular and molecular changes involved in each process. Specifically, the article explores the markers and pathways associated with immune exhaustion, such as PD-1 and TIM-3, and senescence, including Β-galactosidase (ß-GAL), lamin B1, and p16ink4a, and their impact on autoimmune diseases, namely type 1 diabetes, rheumatoid arthritis, systemic lupus erythematosus, and immune-mediated myopathies. Understanding the mechanisms underlying innate immune exhaustion and senescence in autoimmunity may provide insights for the development of novel therapeutic strategies.
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Enfermedades Autoinmunes , Senescencia Celular , Inmunidad Innata , Humanos , Inmunidad Innata/inmunología , Enfermedades Autoinmunes/inmunología , Senescencia Celular/inmunología , Autoinmunidad/inmunología , Agotamiento del Sistema InmunológicoRESUMEN
Introduction: Chronic Pelvic Pain Syndrome or Chronic Prostatitis (CPPS/CP) is the most prevalent urologic affliction among young adult men. It is a challenging condition to treat, which significantly decreases patient quality of life, mostly because of its still uncertain aetiology. In that regard, an autoimmune origin is a prominent supported theory. Indeed, studies in patients and in rodent models of Experimental Autoimmune Prostatitis (EAP) have provided compelling evidence suggesting a key role of CD4 Th1 cells in disease pathogenesis. However, the implication of other prominent effectors of the immune system, such as CD8 T cells, has yet to be studied. Methods: We herein analyzed the induction of prostatitis and the development of chronic pelvic pain in EAP using CD8 T cell-deficient animals. Results: We found similarly elevated PA-specific immune responses, with high frequencies of specific IFNg+CD4+ and IL17+CD4+ T cells in prostate draining lymph nodes from PA-immunized either CD8 KO or wild type animals with respect to controls. Moreover, these peripheral immune responses were paralleled by the development of significant chronic pelvic pain, and accompanied by prostate histological lesions, characterized by hemorrhage, epithelial cell desquamation, marked periglandular leukocyte infiltration, and increased collagen deposition in both, PA-immunized CD8 KO and wild type animals. As expected, control animals did not develop prostate histological lesions. Discussion: Our results indicate that CD8 T cells do not play a major role in EAP pathogenesis and chronic pelvic pain development. Moreover, our results corroborate the previous notion that a CD4 Th1 associated immune response drives the induction of prostate tissue inflammation and the development of chronic pelvic pain.
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Enfermedades Autoinmunes , Linfocitos T CD8-positivos , Modelos Animales de Enfermedad , Ratones Noqueados , Dolor Pélvico , Prostatitis , Prostatitis/inmunología , Prostatitis/patología , Masculino , Animales , Linfocitos T CD8-positivos/inmunología , Dolor Pélvico/inmunología , Enfermedades Autoinmunes/inmunología , Ratones , Dolor Crónico/inmunología , Linfocitos T CD4-Positivos/inmunología , Ratones Endogámicos C57BL , Próstata/inmunología , Próstata/patologíaRESUMEN
OBJECTIVE: To evaluate the IgE reactivity of sera in patients suffering from type 1 diabetes (T1D), lupus nephritis (LN) and juvenile idiopathic arthritis (JIA) against a molecule constructed from T epitopes of A. lumbricoides allergens. METHODS: We designed and expressed a synthetic multi-epítope protein named MP1 from A. lumbricoides and house dust mites allergens. By indirect ELISA, we evaluated IgE-reactivity to MP1 and to the whole-body extract of Ascaris lumbricoides in 45 sera from Colombian Caribbean patients with lupus nephritis (LN; n=25), type 1 diabetes (T1D; n=10) and Juvenil idiopathic arthritis (JIA; n=10). Individuals with poly autoimmunity were excluded. All patients were referred to the study by their specialist doctor. RESULTS: IgE to whole-body extract of A. lumbricoides showed the following median concentrations.484.2 ng/ml (IQR: 203.4) in JIA patients, 325.6 ng/ml (IQR: 179.3) in individuals with LN, and 424.7 ng/ml (IQR: 80.1) in the T1D group. On the other hand, IgE-reactivity to MP1 was 126.4 ng/ml (IQR: 90.9) in JIA patients, 130.7 ng/ml (IQR: 94.8) in an individual with LN, and 148.8 ng/ml (IQR: 102.1) in the T1D group. Although no statistical differences were observed between patient groups, the IgE to MP1 in all patients (n: 45) (IgE median: 134.2 ng/ml; IQR: 100) were significantly less compared to Ascaris extract (IgE median: 380.7 ng/ml; IQR: 175.8); (W: 0.732; p-value: 1.034x10-7). CONCLUSIONS: These preliminary results suggest that MP1 showed antigenic properties with low IgE- reactivity, compared to Ascaris lumbricoides extracted in individuals with autoimmune diseases. Further studies are needed to understand better the immune response induced by this molecule.
OBJETIVO: Evaluar la reactividad IgE de sueros en pacientes que padecen diabetes tipo 1 (DT1), nefritis lúpica (NL) y artritis idiopática juvenil (AIJ) frente a una molécula construida a partir de epítopes T de alérgenos de A. lumbricoides. MÉTODOS: Se diseñó y expresó una proteína multi-epítopes sintética (MP1), a partir de alérgenos de A. lumbricoides y ácaros del polvo doméstico. Mediante ELISA indirecto, se evaluaron las reactividades IgE anti-MP1 y al extracto de cuerpo entero de Ascaris lumbricoides, en sueros de pacientes con nefritis lúpica (NL; n=25), diabetes tipo 1 (T1D; n=10) y artritis idiopática juvenil (AIJ; n=10), procedentes del Caribe colombiano. Se excluyeron los individuos con poliautoinmunidad. Todos los pacientes fueron remitidos al estudio por su médico especialista. RESULTADOS: La IgE frente al extracto de cuerpo completo de A. lumbricoides mostró concentraciones de 484,2 ng/ml (RIQ: 203,4) en pacientes con AIJ; 325,6 ng/ml (RIQ: 179,3) en individuos con NL; y 424,7 ng/ml (RIQ: 80,1) en el grupo con DT1. Por otra parte, la reactividad de IgE anti-MP1 fue de 126,4 ng/ml (RIQ: 90,9) en los pacientes con AIJ; 130,7 ng/ml (RIQ: 94,8) en los individuos con NL; y 148,8 ng/ml (RIQ: 102,1) en el grupo con DT1. Aunque no se observaron diferencias estadísticas entre los grupos de pacientes, la reactividad IgE anti- MP1 en todos los pacientes (n: 45) (mediana de IgE: 134,2 ng/ml; RIQ: 100), fue significativamente inferior en comparación con el extracto de Ascaris (mediana de IgE: 380,7 ng/ml; RIQ: 175,8); (W: 0,732; p-valor: 1,034x10-7). CONCLUSIONES: Estos resultados preliminares sugieren que MP1 mostró propiedades antigénicas con baja reactividad IgE, en comparación con el extracto de Ascaris lumbricoides en individuos con enfermedades autoinmunes. Se necesitan más estudios para comprender mejor la respuesta inmunitaria inducida por esta molécula.
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Alérgenos , Ascaris lumbricoides , Inmunoglobulina E , Humanos , Animales , Ascaris lumbricoides/inmunología , Inmunoglobulina E/sangre , Inmunoglobulina E/inmunología , Alérgenos/inmunología , Femenino , Masculino , Enfermedades Autoinmunes/inmunología , Enfermedades Autoinmunes/sangre , Adolescente , Niño , Epítopos de Linfocito T/inmunología , AdultoRESUMEN
INTRODUCTION: Cardiovascular diseases are the result of genetic and environmental interaction that conditions the integrity of the heart and blood vessels. Risk factors include infections. The inflammatory response against the infectious agent is a trigger of autoimmune cardiovascular diseases due to the similarity between the pathogen proteins and human antigens, since the immune response can present cross-reactivity caused by molecular mimicry. METHODS: We performed a search for pathogens involved in autoimmune heart diseases and autoantigens 9 associated with these diseases in the Pubmed and Google Scholar search engines. Identity between proteins was performed through global alignments using PSI-BLAST. The 3D structures of the proteins were obtained by Uniprot or NCBI and, if not found, the structure was modeled by homology using the Swiss Model server. Epitope prediction was performed through Ellipro and the Immunological Epitope Database (IEDB). In addition, the PYMOL program was used to visualize proteins in 3D and position the epitopes in the structure. RESULTS: A total of ten cardiovascular proteins showed identity (30-88,24%) in their amino acid sequences with antigens from 10 pathogens. Actin proteins and heat shock protein (HSP) families had higher levels of identity with Trypanosoma Cruzi, Cryptococcus neoformans, and Chlamydia trachomatis, 71,47%, 88,24%, and 80,61%, respectively. Other pathogens, such as Streptococcus pyogenes, Bacillus sp, Magnetospirillum gryphiswaldense, Helicobacter pylori and Chlamydia pneumoniae, presented a moderate identity with a maximum value of 65,79%. CONCLUSION: Human actin and HSPs share a high degree of conservation with epitopes from various microorganisms, such as bacteria, fungi and protozoa, suggesting molecular mimicry and cross-reactivity as a mechanism for the development of atherosclerosis, heart disease rheumatic disease, myocarditis and Chagas heart disease. In vitro and in vivo work is needed to demonstrate the results obtained in the In Silico analysis.
INTRODUCCIÓN: Las enfermedades cardiovasculares son el resultado de la interacción genética y ambiental que condiciona la integridad del corazón y los vasos sanguíneos. Los factores de riesgo incluyen infecciones. La respuesta inflamatoria contra el agente infeccioso es un desencadenante de las enfermedades cardiovasculares autoinmunes, debido a la similitud entre las proteínas del patógeno y los antígenos humanos, pues la respuesta inmunitaria puede presentar reactividad cruzada causada por mimetismo molecular. MÉTODOS: Realizamos una búsqueda de patógenos involucrados en enfermedades cardíacas autoinmunes y de autoantígenos asociados a estas enfermedades en los buscadores Pubmed y Google Scholar. La identidad entre proteínas se realizó a través de alineamientos globales utilizando PSI-BLAST. Las estructuras 3D de las proteínas fue obtenida por Uniprot o NCBI y, si no se encontraban, las estructuras se modelaban por homología, utilizando el servidor Swiss Model. La predicción de los epítopes se realizó a través de Ellipro, y la Base de Datos de Epítopos Inmunológicos (IEDB). Además, se utilizó el programa PYMOL para la visualización de proteínas en 3D, y el posicionamiento de los epítopes en la estructura. RESULTADOS: Diez proteínas cardiovasculares mostraron una identidad (30-88,24%) en sus secuencias de aminoácidos con antígenos de diez patógenos. Las proteínas de actina y las familias de proteínas de choque térmico (HSP, por sus siglas en inglés), presentaron niveles de identidad más altos con Trypanosoma Cruzi, Cryptococcus neoformans y Chlamydia trachomatis, 71,47%, 88,24% y 80,61%, respectivamente. Otros patógenos, como Streptococcus pyogenes, Bacillus sp, Magnetospirillum gryphiswaldense, Helicobacter pylori y Chlamydia pneumoniae, presentaron identidad moderada con un valor máximo del 65,79%. CONCLUSIÓN: La actina humana y las HSP comparten un alto grado de conservación con epítopos de varios microorganismos, como bacterias, hongos y protozoos; lo que sugiere la imitación molecular y la reactividad cruzada como mecanismos para el desarrollo de la aterosclerosis, la enfermedad cardíaca reumática, la miocarditis y la enfermedad cardíaca de Chagas. Se necesitan trabajos in vitro e in vivo, que demuestren los resultados obtenidos en el análisis In Silico.
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Enfermedades Cardiovasculares , Imitación Molecular , Humanos , Imitación Molecular/inmunología , Antígenos Bacterianos/inmunología , Autoantígenos/inmunología , Enfermedades Autoinmunes/inmunologíaRESUMEN
PURPOSE: To report two cases of non-granulomatous unilateral anterior uveitis in two female patients associated with autoimmune liver diseases (ALD), emphasizing the possibility of this rare coexistence as a polyautoimmunity phenomenon. CASE DESCRIPTIONS: Case 1: An 18-year-old female with a history of congenital renal hypoplasia and metabolic syndrome presented with anterior uveitis in OS and a history of jaundice, blood elevated hepatic enzymes, and cholangioresonance compatible with primary sclerosing cholangitis (PSC). Laboratory work-up for additional autoimmune and infective causes were within normal limits. Case 2: An 58-year-old female presented an episode of anterior uveitis in OD and a history of Sjögren syndrome diagnosed at the age of 53, primary biliary cholangitis (PBC), systemic sclerosis, Raynaud's phenomenon, bilateral sacroiliitis, and vitiligo, consistent with polyautoimmunity and multiple autoimmune syndrome. CONCLUSIONS: Uveitis rarely coexists with ALD. However, it is essential to recognize the possibility of polyautoimmunity in patients presenting with ophthalmic manifestations and a previous diagnosis of ALD, such as PSC or PBC.
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Enfermedades Autoinmunes , Uveítis Anterior , Humanos , Femenino , Adolescente , Persona de Mediana Edad , Enfermedades Autoinmunes/diagnóstico , Enfermedades Autoinmunes/inmunología , Enfermedades Autoinmunes/complicaciones , Uveítis Anterior/diagnóstico , Uveítis Anterior/inmunologíaRESUMEN
PURPOSE: To present an atypical case of severe bilateral ocular toxoplasmosis with systemic involvement that initially mimicked an autoimmune etiology, posing challenges to its diagnosis and treatment. CASE REPORT: A 39-year-old immunocompetent male was admitted to the hospital due to a presumed pulmonary thromboembolism concomitant with an abrupt onset of vision loss. Initial differential diagnoses included antiphospholipid syndrome and systemic lupus erythematosus, prompting the administration of corticosteroid pulses and rituximab. Despite observing a partial systemic response, there was no improvement in visual acuity. Subsequent aqueous humor polymerase chain reaction confirmed Toxoplasma gondii infection, leading to the introduction of oral antibiotic therapy. The patient's condition showed a partially favorable response; however, the treatment could not reverse the permanent retinal damage. CONCLUSION AND IMPORTANCE: This case underscores the importance of ruling out an infectious etiology in all cases of uveitis. Additionally, it alerts clinicians to the possibility that elevated positive autoantibodies may result from a severe inflammatory reaction caused by pathogens rather than an autoimmune or autoinflammatory disease, particularly in instances of poor treatment response or atypical clinical presentation.
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Enfermedades Autoinmunes , Toxoplasma , Toxoplasmosis Ocular , Humanos , Masculino , Adulto , Toxoplasmosis Ocular/diagnóstico , Toxoplasmosis Ocular/tratamiento farmacológico , Diagnóstico Diferencial , Toxoplasma/inmunología , Toxoplasma/aislamiento & purificación , Enfermedades Autoinmunes/diagnóstico , Enfermedades Autoinmunes/tratamiento farmacológico , Enfermedades Autoinmunes/inmunología , Humor Acuoso/parasitología , Agudeza Visual/fisiología , ADN Protozoario/análisis , Glucocorticoides/uso terapéutico , Lupus Eritematoso Sistémico/diagnóstico , Lupus Eritematoso Sistémico/complicaciones , Lupus Eritematoso Sistémico/tratamiento farmacológico , Infecciones Parasitarias del Ojo/diagnóstico , Infecciones Parasitarias del Ojo/tratamiento farmacológico , Infecciones Parasitarias del Ojo/parasitología , Síndrome Antifosfolípido/diagnóstico , Síndrome Antifosfolípido/tratamiento farmacológico , Síndrome Antifosfolípido/complicaciones , Reacción en Cadena de la PolimerasaRESUMEN
The development of B cells into antibody-secreting plasma cells is central to the adaptive immune system as they induce protective and specific antibody responses against invading pathogens. Various studies have shown that, during this process, hormones can play important roles in the lymphopoiesis, activation, proliferation, and differentiation of B cells, and depending on the signal given by the receptor of each hormone, they can have a positive or negative effect. In autoimmune diseases, hormonal deregulation has been reported to be related to the survival, activation and/or differentiation of autoreactive clones of B cells, thus promoting the development of autoimmunity. Clinical manifestations of autoimmune diseases have been associated with estrogens, prolactin (PRL), and growth hormone (GH) levels. However, androgens, such as testosterone and progesterone (P4), could have a protective effect. The objective of this review is to highlight the links between different hormones and the immune response mediated by B cells in the etiopathogenesis of systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), and multiple sclerosis (MS). The data collected provide insights into the role of hormones in the cellular, molecular and/or epigenetic mechanisms that modulate the B-cell response in health and disease.
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Autoinmunidad , Linfocitos B , Humanos , Linfocitos B/inmunología , Animales , Hormonas/metabolismo , Hormonas/inmunología , Enfermedades Autoinmunes/inmunología , Diferenciación Celular/inmunología , Lupus Eritematoso Sistémico/inmunologíaRESUMEN
Regulatory T cells play a crucial role in the homeostasis of the immune response. Regulatory T cells are mainly generated in the thymus and are characterized by the expression of Foxp3, which is considered the regulatory T-cell master transcription factor. In addition, regulatory T cells can be induced from naive CD4+ T cells to express Foxp3 under specific conditions both in vivo (peripheral regulatory T cells) and in vitro (induced regulatory T cells). Both subsets of thymic regulatory T cells and peripheral regulatory T cells are necessary for the establishment of immune tolerance to self and non-self antigens. Although it has been postulated that induced regulatory T cells may be less stable compared to regulatory T cells, mainly due to epigenetic differences, accumulating evidence in animal models shows that induced regulatory T cells are stable in vivo and can be used for the treatment of inflammatory disorders, including autoimmune diseases and allogeneic transplant rejection. In this review, we describe the biological characteristics of induced regulatory T cells, as well as the key factors involved in induced regulatory T-cell transcriptional, metabolic, and epigenetic regulation, and discuss recent advances for de novo generation of stable regulatory T cells and their use as immunotherapeutic tools in different experimental models. Moreover, we discuss the challenges and considerations for the application of induced regulatory T cells in clinical trials and describe the new approaches proposed to achieve in vivo stability, including functional or metabolic reprogramming and epigenetic editing.
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Autoinmunidad , Linfocitos T Reguladores , Linfocitos T Reguladores/inmunología , Humanos , Animales , Inmunoterapia/métodos , Trasplante Homólogo , Epigénesis Genética , Enfermedades Autoinmunes/inmunología , Enfermedades Autoinmunes/terapia , Rechazo de Injerto/inmunología , Factores de Transcripción Forkhead/metabolismoRESUMEN
INTRODUCTION: For the diagnosis of liver diseases, clinical criteria, biochemical, immunological and histological parameters are included. The autoimmune panel is an immunoblot that contemplates the detection of antibodies against 9 different hepatic antigens, which could guide the diagnosis of these pathologies. OBJECTIVE: To describe the usefulness of the autoimmune panel in the diagnosis of liver diseases. Methods: Observational, descriptive study. All autoimmune panels performed between January 2020 and August 2021 (n = 279) were reviewed, and the ones with positive result selected (n = 101). Clinical records were reviewed, including: clinical, biochemical, immunological and histological characteristics. Diagnosis was determined by clinical suspicion (clinical, biochemical and immunological parameters), only through autoimmune panel, and according to liver biopsy in available cases. RESULTS: 45 patients with complete clinical history were included in the analysis; 82% women, median age 58 years (16-79). Clinical suspicions included autoimmune hepatitis (AIH) in 12 patients (27%), primary biliary cholangitis (PBC) in 10 patients (22%), overlap syndrome (AIH/PBC) in 17 (38%), and others in 6 (13%). The diagnosis of PBC was confirmed by autoimmune panel in 9/10 and 11/17 patients with clinical suspicion of PBC and HAI/PBC, respectively. Of the 27 patients with initial clinical suspicion of PBC, 14 had negative AMA and AMA-M2 (6 had Sp100 and 5 gp210 as the only markers and 3 had positive Sp100 and PML). In 10/14 patients, the diagnosis was confirmed by panel and/or compatible liver biopsy. CONCLUSION: The autoimmune panel turns out to be a useful diagnostic tool for liver diseases, especially PBC in isolation or in overlap syndrome.
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Humanos , Masculino , Femenino , Adolescente , Adulto , Persona de Mediana Edad , Anciano , Adulto Joven , Autoanticuerpos/sangre , Immunoblotting/métodos , Hepatitis Autoinmune/diagnóstico , Hepatitis Autoinmune/inmunología , Hepatitis Autoinmune/sangre , Hepatopatías/diagnóstico , Hepatopatías/inmunología , Enfermedades Autoinmunes/diagnóstico , Enfermedades Autoinmunes/inmunología , Enfermedades Autoinmunes/sangre , Cirrosis Hepática Biliar/diagnóstico , Cirrosis Hepática Biliar/inmunología , Cirrosis Hepática Biliar/sangreRESUMEN
INTRODUCTION: For the diagnosis of liver diseases, clinical criteria, biochemical, immunological and histological parameters are included. The autoimmune panel is an immunoblot that contemplates the detection of antibodies against 9 different hepatic antigens, which could guide the diagnosis of these pathologies. OBJECTIVE: To describe the usefulness of the autoimmune panel in the diagnosis of liver diseases. METHODS: Observational, descriptive study. All autoimmune panels performed between January 2020 and August 2021 (n = 279) were reviewed, and the ones with positive result selected (n = 101). Clinical records were reviewed, including: clinical, biochemical, immunological and histological characteristics. Diagnosis was determined by clinical suspicion (clinical, biochemical and immunological parameters), only through autoimmune panel, and according to liver biopsy in available cases. RESULTS: 45 patients with complete clinical history were included in the analysis; 82% women, median age 58 years (16-79). Clinical suspicions included autoimmune hepatitis (AIH) in 12 patients (27%), primary biliary cholangitis (PBC) in 10 patients (22%), overlap syndrome (AIH/PBC) in 17 (38%), and others in 6 (13%). The diagnosis of PBC was confirmed by autoimmune panel in 9/10 and 11/17 patients with clinical suspicion of PBC and HAI/PBC, respectively. Of the 27 patients with initial clinical suspicion of PBC, 14 had negative AMA and AMA-M2 (6 had Sp100 and 5 gp210 as the only markers and 3 had positive Sp100 and PML). In 10/14 patients, the diagnosis was confirmed by panel and/or compatible liver biopsy. CONCLUSION: The autoimmune panel turns out to be a useful diagnostic tool for liver diseases, especially PBC in isolation or in overlap syndrome.
Asunto(s)
Autoanticuerpos , Hepatitis Autoinmune , Immunoblotting , Hepatopatías , Humanos , Femenino , Autoanticuerpos/sangre , Masculino , Persona de Mediana Edad , Adulto , Anciano , Adolescente , Adulto Joven , Immunoblotting/métodos , Hepatitis Autoinmune/inmunología , Hepatitis Autoinmune/diagnóstico , Hepatitis Autoinmune/sangre , Hepatopatías/inmunología , Hepatopatías/diagnóstico , Cirrosis Hepática Biliar/inmunología , Cirrosis Hepática Biliar/diagnóstico , Cirrosis Hepática Biliar/sangre , Enfermedades Autoinmunes/inmunología , Enfermedades Autoinmunes/diagnóstico , Enfermedades Autoinmunes/sangreRESUMEN
BACKGROUND: Identification of biomarkers associated with immune-mediated diseases in 22q11.2 deletion syndrome is an evolving field. OBJECTIVES: We sought to use a carefully phenotyped cohort to study immune parameters associated with autoimmunity and atopy in 22q11.2 deletion syndrome to define biomarkers associated with immune-mediated disease in this syndrome. METHODS: Chart review validated autoimmune disease and atopic condition diagnoses. Laboratory data were extracted for each subcohort and plotted according to age. A random-effects model was used to define statistical significance. RESULTS: CD19, CD4, and CD4/45RA lymphocyte populations were not different from the general cohort for patients with atopic conditions. CD4/45RA T cells were significantly lower in the subjects with immune thrombocytopenia compared with the general cohort, and CD4 T-cell counts were lower in patients with autoimmune thyroid disease. CONCLUSIONS: The mechanisms of autoimmunity in cytopenias may be distinct from those of solid-organ autoimmunity in 22q11.2 deletion syndrome. This study identifies potential biomarkers for risk stratification among commonly obtained laboratory studies.
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Enfermedades Autoinmunes/inmunología , Linfocitos T CD4-Positivos/inmunología , Síndrome de DiGeorge/inmunología , Hipersensibilidad Inmediata/inmunología , Adolescente , Adulto , Recuento de Linfocito CD4 , Niño , Preescolar , Femenino , Humanos , Lactante , Masculino , Fenotipo , Adulto JovenRESUMEN
There is growing evidence that coronavirus disease 2019 (COVID-19) can lead to a dysregulation of the immune system with the development of autoimmune phenomena. The consequence of this immune dysregulation ranges from the production of autoantibodies to the onset of rheumatic autoimmune disease. In this context, we conducted a systematic review to analyze the current data regarding the new-onset systemic and rheumatic autoimmune diseases in COVID-19 patients. A literature search in PubMed and Scopus databases from December 2019 to September 2021 identified 99 patients that fulfilled the specific diagnostic/classification criteria and/or nomenclature for each rheumatic autoimmune disease. The main diseases reported were vasculitis and arthritis. Idiopathic inflammatory myopathies, systemic lupus erythematosus, and sarcoidosis were also reported in a limited number of patients, as well as isolated cases of systemic sclerosis and adult-onset Still's disease. These findings highlight the potential spectrum of systemic and rheumatic autoimmune diseases that could be precipitated by SARS-CoV-2 infection. Complementary studies are needed to discern the link between the SARS-CoV-2 and new onset-rheumatic diseases so that this knowledge can be used in early diagnosis and the most suitable management.
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Enfermedades Autoinmunes , Prueba de COVID-19 , COVID-19 , SARS-CoV-2/inmunología , Enfermedades Autoinmunes/diagnóstico , Enfermedades Autoinmunes/etiología , Enfermedades Autoinmunes/inmunología , COVID-19/complicaciones , COVID-19/inmunología , HumanosRESUMEN
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.
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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
Results of the anti-nuclear antibodies-indirect immunofluorescence assay (anti-cell antibodies test) on HEp-2 cell substrates should be communicated to clinicians in a standardized way, adding value to laboratory findings and helping with critical clinical decisions. This paper proposes a test report based on the practices informed by 118 laboratories in 68 countries, with recommendations from the International Consensus on ANA Patterns (ICAP) group. Major focus is placed on the report format containing endpoint titers, immunofluorescence patterns together with anti-cell (AC) nomenclature, remarks on follow-up or reflex testing, and possible other autoantibody associations. ISO 15,189 directives were integrated into the test report. Special situations addressed include serum screening dilutions and endpoint titers, relevance of immunofluorescence patterns with special attention to cytoplasmic patterns, mixed and compound patterns, and how to report different titers corresponding to multiple patterns or autoantibodies in the same sample. This paper suggests a subtitle for the HEp-2-IIFA, namely anti-cell antibodies test, which could gradually substitute the original outdated ANA nomenclature. This ICAP pro forma report represents a further step in harmonizing the way relevant clinical information could be provided by laboratories.
Asunto(s)
Anticuerpos Antinucleares/inmunología , Enfermedades Autoinmunes/inmunología , Línea Celular , Consenso , Técnica del Anticuerpo Fluorescente Indirecta , Humanos , Guías de Práctica Clínica como AsuntoRESUMEN
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.