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Autoimmune diseases (ADs) showcase the intricate balance between the immune system's protective functions and its potential for self-inflicted damage. These disorders arise from the immune system's erroneous targeting of the body's tissues, resulting in damage and disease. The ability of T cells to distinguish between self and non-self-antigens is pivotal to averting autoimmune reactions. Perturbations in this process contribute to AD development. Autoreactive T cells that elude thymic elimination are activated by mimics of self-antigens or are erroneously activated by self-antigens can trigger autoimmune responses. Various mechanisms, including molecular mimicry and bystander activation, contribute to AD initiation, with specific triggers and processes varying across the different ADs. In addition, the formation of neo-epitopes could also be implicated in the emergence of autoreactivity. The specificity of T cell responses centers on the antigen recognition sequences expressed by T cell receptors (TCRs), which recognize peptide fragments displayed by major histocompatibility complex (MHC) molecules. The assortment of TCR gene combinations yields a diverse array of T cell populations, each with distinct affinities for self and non-self antigens. However, new evidence challenges the traditional notion that clonal expansion solely steers the selection of higher-affinity T cells. Lower-affinity T cells also play a substantial role, prompting the "two-hit" hypothesis. High-affinity T cells incite initial responses, while their lower-affinity counterparts perpetuate autoimmunity. Precision treatments that target antigen-specific T cells hold promise for avoiding widespread immunosuppression. Nevertheless, detection of such antigen-specific T cells remains a challenge, and multiple technologies have been developed with different sensitivities while still harboring several drawbacks. In addition, elements such as human leukocyte antigen (HLA) haplotypes and validation through animal models are pivotal for advancing these strategies. In brief, this review delves into the intricate mechanisms contributing to ADs, accentuating the pivotal role(s) of antigen-specific T cells in steering immune responses and disease progression, as well as the novel strategies for the identification of antigen-specific cells and their possible future use in humans. Grasping the mechanisms behind ADs paves the way for targeted therapeutic interventions, potentially enhancing treatment choices while minimizing the risk of systemic immunosuppression.
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Human T-lymphotropic virus type 1 (HTLV-1) is classically associated with the HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP), although the mechanisms of this neurological disorder remain unclear. In addition, some patients who develop "minor" neurological signs that do not meet diagnostic criteria for HAM/TSP are classified as asymptomatic carriers. This study aims to demonstrate the neurological symptoms of Brazilian patients living with HTLV-1 classified as not-HAM.TSP. This observational study evaluated patients treated in an HTLV reference center in Bahia, Brazil, between February 2022 and July 2023. The data were obtained through the analysis of medical records and neurological consultation. Those individuals classified as HAM/ TSP were excluded from this study. 74 patients were submitted to a careful neurological evaluation: 23 HAM/TSP, 22 were classified with intermediate syndrome (IS), and 29 were oligosymptomatic. Self-reported symptoms were significantly more common in the IS group, including urinary symptoms such as nocturia, urgency, incontinence, dysuria, weakness, paresthesia, lumbar pain, xerostomia, and xerophthalmia. Physical examination findings consistent with reduced vibratory and tactile sensitivity were more common in the IS group (p = 0.017 and p = 0.013). Alterations in the V and VIII cranial nerves were present in both groups. HTLV-1 can lead to the development of important neurological signs and symptoms in apparently asymptomatic individuals. This data highlights the need for more research into the neurological aspects of HTLV-1 infection and emphasizes the importance of early diagnosis, treatment, and support for individuals living with this virus.
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INTRODUCTION: Glaucoma is a neurodegenerative disease characterized by the loss of retinal ganglion cells. Recent research suggests immunological changes such as cytokine imbalance may affect its pathophysiology. This implies that immunomodulation, like that of mesenchymal cells, could be a potential therapeutic avenue for this disease. However, the effects of intravitreal injections of human Wharton's jelly-derived mesenchymal stromal cells (hWJ-MSCs) on intraocular immune response have not been assessed in ocular hypertension (OH) models. METHODS: We explored this by measuring cytokine levels and expression of other markers, such as glial fibrillary acidic protein (GFAP) and T cells, in 15 randomly divided New Zealand rabbits: G1: OH, G2: hWJ-MSCs, and G3: OH+hWJ-MSCs. We analyzed the aqueous humor (IL-6, IL-8, and TNF-α) and vitreous humor (IFN-γ, IL-10, and TGF-ß) using ELISA and flow cytometry (cell populations), as well as TCD3+, TCD3+/TCD4+, and TCD3+/TCD8+ lymphocytes, and GFAP in the retina and optic nerve through immunohistochemistry. RESULTS: We found a decrease in TNF-α, IL-6, IFN-γ, IL-10, and IL-8 in G3 compared to G1 and an increase in TGF-ß in both G2 and G3. TCD3+ retinal infiltration in all groups was primarily TCD8+ rather than TCD4+ cells, and strong GFAP expression was observed in both the retina and optic nerves in all groups. CONCLUSION: Our results suggest that cellular and humoral immune responses may play a role in glaucomatous optic neuropathy and that intravitreal hWJ-MSCs can induce an immunosuppressive environment by inhibiting proinflammatory cytokines and enhancing regulatory cytokines.
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Citocinas , Modelos Animales de Enfermedad , Ensayo de Inmunoadsorción Enzimática , Células Madre Mesenquimatosas , Hipertensión Ocular , Gelatina de Wharton , Animales , Conejos , Gelatina de Wharton/citología , Humanos , Hipertensión Ocular/metabolismo , Citocinas/metabolismo , Humor Acuoso/metabolismo , Presión Intraocular/fisiología , Citometría de Flujo , Trasplante de Células Madre Mesenquimatosas/métodos , Inyecciones Intravítreas , Inmunohistoquímica , Células Ganglionares de la Retina/patología , Glucocorticoides , Nervio Óptico/patologíaRESUMEN
STATEMENT OF PROBLEM: The gingival zenith (GZ) influences the line angle position in the emergence profile and the axial inclination of the crown. Irregularities in GZ symmetry and contour have a negative impact on dental esthetics. GZ location is not consistently distal to the crown's long axis; instead, it tends to be more distal in anterior teeth. The GZ levelling of the lateral incisor is often described as either level with or slightly above the zenith line connecting the central incisor and canine teeth, but there are also reports of GZ being aligned apically to the zenith line. Controversial reports persist regarding GZ positioning, magnitude, and location, potentially leading to inadequate positioning and levelling of the GZ in esthetic restorative therapy. PURPOSE: The purpose of this systematic review and meta-analysis was to assess the scientific evidence related to GZ level, position, and symmetry in maxillary incisors and canines. MATERIAL AND METHODS: This study adhered to the population, variable, outcome (PVO) criteria and the preferred reporting items for systematic reviews and meta-analysis (PRISMA) checklist. Cross-sectional studies involving healthy adults with complete dentition of the maxillary anterior sextant were subjected to prevalence analysis and quantitative measurement to assess the gingival zenith level and position. Data were extracted, and methodological quality was appraised using the Joanna Briggs Institute critical appraisal checklist for analytical cross-sectional studies. Certainty of evidence was evaluated through the grading of recommendations, assessment, development, and evaluation (GRADE) system. RESULTS: The GZs were distally positioned, coinciding with the tooth axis or mesially positioned in, respectively, 96%, 3%, and 1% on central incisors; 84%, 14%, and 1% on lateral incisors; and 43%, 44%, and 5% on canines. GZ distal positioning was greater in central incisors, followed by lateral incisors and canines. In lateral incisors, the GZ was levelled coronally in 82% of the population. Contralateral symmetry was observed for GZ levelling and positioning. The certainty of the evidence was very low for all comparisons. CONCLUSIONS: The frequency and magnitude of the distal position of the GZ increased the more anterior the tooth. Axially, the GZ was frequently levelled coronally to the zenith line. The contralateral positioning and levelling of the GZ was symmetrical.
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Infectious diseases are commonly implicated as potential initiators of autoimmune diseases (ADs) and represent the most commonly known factor in the development of autoimmunity in susceptible individuals. Epidemiological data and animal studies on multiple ADs suggest that molecular mimicry is one of the likely mechanisms for the loss of peripheral tolerance and the development of clinical disease. Besides molecular mimicry, other mechanisms such as defects in central tolerance, nonspecific bystander activation, epitope-determinant spreading, and/or constant antigenic stimuli, may also contribute for breach of tolerance and to the development of ADs. Linear peptide homology is not the only mechanism by which molecular mimicry is established. Peptide modeling (i.e., 3D structure), molecular docking analyses, and affinity estimation for HLAs are emerging as critical strategies when studying the links of molecular mimicry in the development of autoimmunity. In the current pandemic, several reports have confirmed an influence of SARS-CoV-2 on subsequent autoimmunity. Bioinformatic and experimental evidence support the potential role of molecular mimicry. Peptide dimensional analysis requires more research and will be increasingly important for designing and distributing vaccines and better understanding the role of environmental factors related to autoimmunity.
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Enfermedades Autoinmunes , COVID-19 , Animales , Autoinmunidad , Imitación Molecular , Simulación del Acoplamiento Molecular , SARS-CoV-2 , Enfermedades Autoinmunes/epidemiologíaRESUMEN
BACKGROUND: The immunopathological pathways enabling post-coronavirus disease 2019 (COVID-19) syndrome (PCS) development are not entirely known. We underwent a longitudinal analysis of patients with COVID-19 who developed PCS aiming to evaluate the autoimmune and immunological status associated with this condition. METHODS: Thirty-three patients were included for longitudinal clinical and autoantibody analyses, 12 of whom were assessed for cytokines and lymphocyte populations. Patients were followed for 7-11 months after acute COVID-19. Autoimmune profile and immunological statuses were evaluated mainly by enzyme-linked-immunosorbent assays and flow cytometry. RESULTS: Latent autoimmunity and overt autoimmunity persisted over time. A proinflammatory state was observed in patients with PCS characterized by up-regulated interferon-α, tumor necrosis factor-α, granulocyte colony-stimulating factor (G-CSF), interleukin (IL)-17A, IL-6, IL-1ß, and IL-13, whereas interferon-γ-induced protein 10 (IP-10) was decreased. In addition, PCS was characterized by increased levels of Th9, CD8+ effector T cells, naive B cells, and CD4+ effector memory T cells. Total levels of immunoglobulin G S1-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies remained elevated over time. CONCLUSIONS: The clinical manifestations of PCS are associated with the persistence of a proinflammatory and effector phenotype induced by SARS-CoV-2 infection. This long-term persistent immune activation may contribute to the development of latent and overt autoimmunity. Results suggest the need to evaluate the role of immunomodulation in the treatment of PCS.
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Autoinmunidad , COVID-19 , COVID-19/complicaciones , Citocinas , Humanos , Inflamación , Interferón gamma , SARS-CoV-2 , Síndrome Post Agudo de COVID-19RESUMEN
Long-term adaptive immune memory has been reported among immunocompetent individuals up to eight months following SARS-CoV-2 infection. However, limited data is available in convalescent patients with a solid organ transplant. To investigate this, we performed a thorough evaluation of adaptive immune memory at different compartments (serological, memory B cells and cytokine [IFN-γ, IL-2, IFN-γ/IL12 and IL-21] producing T cells) specific to SARS-CoV-2 by ELISA and FluoroSpot-based assays in 102 convalescent patients (53 with a solid organ transplants (38 kidney, 5 liver, 5 lung and 5 heart transplant) and 49 immunocompetent controls) with different clinical COVID-19 severity (severe, mild and asymptomatic) beyond six months after infection. While similar detectable memory responses at different immune compartments were detected between those with a solid organ transplant and immunocompetent individuals, these responses were predominantly driven by distinct COVID-19 clinical severities (97.6%, 80.5% and 42.1%, all significantly different, were seropositive; 84% vs 75% vs 35.7%, all significantly different, showed IgG-producing memory B cells and 82.5%, 86.9% and 31.6%, displayed IFN-γ producing T cells; in severe, mild and asymptomatic convalescent patients, respectively). Notably, patients with a solid organ transplant with longer time after transplantation did more likely show detectable long-lasting immune memory, regardless of COVID-19 severity. Thus, our study shows that patients with a solid organ transplant are capable of maintaining long-lasting peripheral immune memory after COVID-19 infection; mainly determined by the degree of infection severity.
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COVID-19 , Trasplante de Órganos , Anticuerpos Antivirales , Humanos , Memoria Inmunológica , Trasplante de Órganos/efectos adversos , SARS-CoV-2 , Receptores de TrasplantesRESUMEN
Autoimmunity has emerged as a characteristic of the post-COVID syndrome (PCS), which may be related to sex. In order to further investigate the relationship between SARS-CoV-2 and autoimmunity in PCS, a clinical and serological assessment on 100 patients was done. Serum antibody profiles against self-antigens and infectious agents were evaluated by an antigen array chip for 116 IgG and 104 IgM antibodies. Thirty pre-pandemic healthy individuals were included as a control group. The median age of patients was 49 years (IQR: 37.8 to 55.3). There were 47 males. The median post-COVID time was 219 (IQR: 143 to 258) days. Latent autoimmunity and polyautoimmunity were found in 83% and 62% of patients, respectively. Three patients developed an overt autoimmune disease. IgG antibodies against IL-2, CD8B, and thyroglobulin were found in more than 10% of the patients. Other IgG autoantibodies, such as anti-interferons, were positive in 5-10% of patients. Anti-SARS-CoV-2 IgG antibodies were found in > 85% of patients and were positively correlated with autoantibodies, age, and body mass index (BMI). Few autoantibodies were influenced by age and BMI. There was no effect of gender on the over- or under-expression of autoantibodies. IgG anti-IFN-λ antibodies were associated with the persistence of respiratory symptoms. In summary, autoimmunity is characteristic of PCS, and latent autoimmunity correlates with humoral response to SARS-CoV-2.
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Autoinmunidad , COVID-19 , Adulto , Anticuerpos Antivirales/sangre , Humanos , Inmunoglobulina M/sangre , Masculino , Persona de Mediana Edad , SARS-CoV-2RESUMEN
OBJECTIVE: The clinical coexistence of two or more autoimmune diseases (ADs) fulfilling classification criteria is termed "overt polyautoimmunity" (PolyA), whereas the presence of autoantibodies unrelated to an index AD, without clinical criteria fulfillment, is known as "latent PolyA". We aimed to explore a new taxonomy of ADs based on PolyA. METHODS: In a cross-sectional study of 292 subjects, we evaluated the presence of PolyA in 146, 45, 29, 17, and 17 patients with rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), Sjögren's syndrome (SS), autoimmune thyroid disease (AITD) and systemic sclerosis (SSc), respectively, and 38 healthy controls. Clinical assessment, autoantibody profile (by autoantigen array chip), lymphocytes immunophenotype and cytokine profile (by flow cytometry) were evaluated simultaneously. A mixed cluster methodology was used to classify ADs. RESULTS: Latent PolyA was more frequent than overt PolyA, ranging from 69.9% in RA to 100% in SSc. Nevertheless, both latent and overt PolyA clustered together. Over-expressed IgG autoantibodies were found to be hallmarks for the identification of index ADs. The combination of autoantibodies allowed high accuracy in the classification of ADs. Three well-defined clusters based on PolyA were observed with distinctive clinical and immunological phenotypes. CONCLUSIONS: This proof-of-concept study indicates that ADs can be classified according to PolyA. PolyA should be considered in all studies dealing with ADs, including epidemiological, genetic, and clinical trials.
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Enfermedades Autoinmunes , Lupus Eritematoso Sistémico , Síndrome de Sjögren , Autoanticuerpos , Enfermedades Autoinmunes/complicaciones , Enfermedades Autoinmunes/diagnóstico , Enfermedades Autoinmunes/epidemiología , Autoinmunidad , Estudios Transversales , Humanos , Lupus Eritematoso Sistémico/complicaciones , Lupus Eritematoso Sistémico/diagnóstico , Lupus Eritematoso Sistémico/epidemiología , Síndrome de Sjögren/complicaciones , Síndrome de Sjögren/diagnóstico , Síndrome de Sjögren/epidemiologíaRESUMEN
BACKGROUND: Convalescent plasma (CP) has been widely used to treat COVID-19 and is under study. However, the variability in the current clinical trials has averted its wide use in the current pandemic. We aimed to evaluate the safety and efficacy of CP in severe coronavirus disease 2019 (COVID-19) in the early stages of the disease. METHODS: A randomized controlled clinical study was conducted on 101 patients admitted to the hospital with confirmed severe COVID-19. Most participants had less than 14 days from symptoms onset and less than seven days from hospitalization. Fifty patients were assigned to receive CP plus standard therapy (ST), and 51 were assigned to receive ST alone. Participants in the CP arm received two doses of 250 mL each, transfused 24 h apart. All transfused plasma was obtained from "super donors" that fulfilled the following criteria: titers of anti-SARS-CoV-2 S1 IgG ≥ 1:3200 and IgA ≥ 1:800 antibodies. The effect of transfused anti-IFN antibodies and the SARS-CoV-2 variants at the entry of the study on the overall CP efficacy was evaluated. The primary outcomes were the reduction in viral load and the increase in IgG and IgA antibodies at 28 days of follow-up. The per-protocol analysis included 91 patients. RESULTS: An early but transient increase in IgG anti-S1-SARS-CoV-2 antibody levels at day 4 post-transfusion was observed (Estimated difference [ED], - 1.36; 95% CI, - 2.33 to - 0.39; P = 0.04). However, CP was not associated with viral load reduction in any of the points evaluated. Analysis of secondary outcomes revealed that those patients in the CP arm disclosed a shorter time to discharge (ED adjusted for mortality, 3.1 days; 95% CI, 0.20 to 5.94; P = 0.0361) or a reduction of 2 points on the WHO scale when compared with the ST group (HR adjusted for mortality, 1.6; 95% CI, 1.03 to 2.5; P = 0.0376). There were no benefits from CP on the rates of intensive care unit admission (HR, 0.82; 95% CI, 0.35 to 1.9; P = 0.6399), mechanical ventilation (HR, 0.66; 95% CI, 0.25 to 1.7; P = 0.4039), or mortality (HR, 3.2; 95% CI, 0.64 to 16; P = 0.1584). Anti-IFN antibodies and SARS-CoV-2 variants did not influence these results. CONCLUSION: CP was not associated with viral load reduction, despite the early increase in IgG anti-SARS-CoV-2 antibodies. However, CP is safe and could be a therapeutic option to reduce the hospital length of stay. Trial registration NCT04332835.
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COVID-19 , Infecciones por Coronavirus , Neumonía Viral , Anticuerpos Antivirales , Betacoronavirus , COVID-19/terapia , Humanos , Inmunización Pasiva , Inmunoglobulina A , Inmunoglobulina G/uso terapéutico , SARS-CoV-2 , Resultado del Tratamiento , Sueroterapia para COVID-19RESUMEN
Convalescent plasma (CP) has emerged as a treatment for COVID-19. However, the composition and mechanism of action are not fully known. Therefore, we undertook a two-phase controlled study in which, first the immunological and metabolomic status of recovered and severe patients were evaluated. Secondly, the 28-day effect of CP on the immune response in severe patients was assessed. Nineteen recovered COVID-19 patients, 18 hospitalized patients with severe disease, and 16 pre-pandemic controls were included. Patients with severe disease were treated with CP transfusion and standard therapy (i.e., plasma recipients, n = 9) or standard therapy alone (n = 9). Clinical and biological assessments were done on day 0 and during follow-up on days 4, 7, 14, and 28. Clinical parameters, viral load, total immunoglobulin (Ig) G and IgA anti-S1-SARS-CoV-2 antibodies, neutralizing antibodies (NAbs), autoantibodies, cytokines, T and B cells, and metabolomic and lipidomic profiles were examined. Total IgG and IgA anti-S1-SARS-CoV-2 antibodies were key factors for CP selection and correlated with NAbs. In severe COVID-19 patients, mostly interleukin (IL)-6 (P = <0.0001), IL-10 (P = <0.0001), IP-10 (P = <0.0001), fatty acyls and glycerophospholipids were higher than in recovered patients. Latent autoimmunity and anti-IFN-α antibodies were observed in both recovered and severe patients. COVID-19 CP induced an early but transient cytokine profile modification and increases IgG anti-S1-SARS-CoV-2 antibodies. At day 28 post-transfusion, a decrease in activated, effector and effector memory CD4+ (P < 0.05) and activated and effector CD8+ (P < 0.01) T cells and naïve B cells (P = 0.001), and an increase in non-classical memory B cells (P=<0.0001) and central memory CD4+ T cells (P = 0.0252) were observed. Moreover, IL-6/IFN-γ (P = 0.0089) and IL-6/IL-10 (P = 0.0180) ratios decreased in plasma recipients compared to those who received standard therapy alone. These results may have therapeutic implications and justify further post-COVID-19 studies.
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Anticuerpos Neutralizantes/sangre , Anticuerpos Antivirales/sangre , COVID-19/terapia , Interleucina-10/sangre , Interleucina-6/sangre , SARS-CoV-2 , Adulto , Linfocitos B/metabolismo , Linfocitos T CD4-Positivos/metabolismo , Linfocitos T CD8-positivos/metabolismo , COVID-19/sangre , Femenino , Humanos , Inmunización Pasiva , Masculino , Persona de Mediana Edad , Índice de Severidad de la Enfermedad , Sueroterapia para COVID-19RESUMEN
OBJECTIVES: The National Pediatric Readiness Project of the Emergency Medical Services for Children surveyed emergency departments in the United States in 2013 for readiness to provide emergency care to children. However, that survey did not query for many elements considered essential to Advanced Trauma Life Support (ATLS). METHODS: Our pediatric trauma center and state department of health collaborated to develop a survey reflecting ATLS principles regarding pediatric-specific trauma stabilization, clinical/administrative resources, and interfacility transfer to complement the 2017 PedsReady survey. We distributed the survey to all emergency department medical directors in our state in 2017. RESULTS: Medical directors of all 11 emergency departments responded. Only 2 reported having physician or nurse pediatric trauma coordinators. Two reported comfort with all emergency procedures at all ages (eg, airway, traumatic pneumothorax treatment, etc), whereas 9 had variable thresholds of comfort by age and procedure. Reported utilization of pediatric trauma-specific protocols varied the following: hyperosmolar therapy (1), neurological assessment (3), chest injury (4), massive transfusion (1), triage (5), trauma transfer agreements (10), imaging-limitation protocols (4), internal (1) and inter-facility (4) quality assurance/quality improvement process (1), and real-time image transfer (11). CONCLUSIONS: This survey identified gaps in the readiness of emergency departments to treat injured children in our state that were not detected by the 2013 PedsReady surveys. Future surveys of emergency department pediatric readiness should consider more detailed, trauma-specific readiness questions. This will allow for assignment of more accurate goals and benchmarking standards for national pediatric trauma readiness.
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Servicios Médicos de Urgencia , Servicio de Urgencia en Hospital , Niño , Humanos , Mejoramiento de la Calidad , Centros Traumatológicos , Triaje , Estados UnidosRESUMEN
The genus Ebolavirus from the family Filoviridae is composed of five species including Sudan ebolavirus, Reston ebolavirus, Bundibugyo ebolavirus, Taï Forest ebolavirus, and Ebola virus (previously known as Zaire ebolavirus). These viruses have a large non-segmented, negative-strand RNA of approximately 19 kb that encodes for glycoproteins (i.e., GP, sGP, ssGP), nucleoproteins, virion proteins (i.e., VP 24, 30,40) and an RNA dependent RNA polymerase. These viruses have become a global health concern because of mortality, their rapid dissemination, new outbreaks in West-Africa, and the emergence of a new condition known as "Post-Ebola virus disease syndrome" that resembles inflammatory and autoimmune conditions such as rheumatoid arthritis, systemic lupus erythematosus and spondyloarthritis with uveitis. However, there are many gaps in the understanding of the mechanisms that may induce the development of such autoimmune-like syndromes. Some of these mechanisms may include a high formation of neutrophil extracellular traps, an uncontrolled "cytokine storm", and the possible formation of auto-antibodies. The likely appearance of autoimmune phenomena in Ebola survivors suppose a new challenge in the management and control of this disease and opens a new field of research in a special subgroup of patients. Herein, the molecular biology, pathogenesis, clinical manifestations, and treatment of Ebola virus disease are reviewed and some strategies for control of disease are discussed.
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Ebolavirus/inmunología , Fiebre Hemorrágica Ebola/inmunología , Fiebre Hemorrágica Ebola/virología , Animales , Anticuerpos Antivirales/inmunología , Autoanticuerpos/inmunología , Diabetes Mellitus Tipo 1/inmunología , Diabetes Mellitus Tipo 1/virología , HumanosRESUMEN
Coronavirus disease 2019 (COVID-19) has been categorized as evolving in overlapping phases. First, there is a viral phase that may well be asymptomatic or mild in the majority, perhaps 80% of patients. The pathophysiological mechanisms resulting in minimal disease in this initial phase are not well known. In the remaining 20% of cases, the disease may become severe and/or critical. In most patients of this latter group, there is a phase characterized by the hyperresponsiveness of the immune system. A third phase corresponds to a state of hypercoagulability. Finally, in the fourth stage organ injury and failure occur. Appearance of autoinflammatory/autoimmune phenomena in patients with COVID-19 calls attention for the development of new strategies for the management of life-threatening conditions in critically ill patients. Antiphospholipid syndrome, autoimmune cytopenia, Guillain-Barré syndrome and Kawasaki disease have each been reported in patients with COVID-19. Here we present a scoping review of the relevant immunological findings in COVID-19 as well as the current reports about autoinflammatory/autoimmune conditions associated with the disease. These observations have crucial therapeutic implications since immunomodulatory drugs are at present the most likely best candidates for COVID-19 therapy. Clinicians should be aware of these conditions in patients with COVID-19, and these observations should be considered in the current development of vaccines.
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Enfermedades Autoinmunes/inmunología , Betacoronavirus/inmunología , Infecciones por Coronavirus/inmunología , Síndrome de Liberación de Citoquinas/inmunología , Neumonía Viral/inmunología , Inmunidad Adaptativa/genética , Enfermedades Autoinmunes/diagnóstico , Enfermedades Autoinmunes/terapia , Enfermedades Autoinmunes/virología , Betacoronavirus/aislamiento & purificación , COVID-19 , Prueba de COVID-19 , Técnicas de Laboratorio Clínico , Infecciones por Coronavirus/diagnóstico , Infecciones por Coronavirus/epidemiología , Infecciones por Coronavirus/terapia , Enfermedad Crítica , Síndrome de Liberación de Citoquinas/diagnóstico , Síndrome de Liberación de Citoquinas/terapia , Síndrome de Liberación de Citoquinas/virología , Femenino , Predisposición Genética a la Enfermedad , Humanos , Inmunidad Innata/genética , Inmunización Pasiva/métodos , Mediadores de Inflamación/sangre , Mediadores de Inflamación/inmunología , Activación de Macrófagos/genética , Activación de Macrófagos/inmunología , Masculino , Pandemias , Neumonía Viral/diagnóstico , Neumonía Viral/epidemiología , Neumonía Viral/terapia , Factores de Riesgo , SARS-CoV-2 , Índice de Severidad de la Enfermedad , Factores Sexuales , Sueroterapia para COVID-19RESUMEN
Chronic inflammatory demyelinating polyneuropathy (CIDP) is an autoimmune disease characterized by neurological symptoms and signs of progressive weakness, paresthesias, and sensory dysfunction. Other symptoms include reduced or absent tendon reflexes, cranial nerve involvement, autonomic symptoms, ataxia, and neuropathic pain. Unlike other autoimmune diseases, CIDP generally affects older individuals and has a male predominance. The onset is generally insidious and can take up to 8 weeks with a relapsing-recovery pattern. Like all autoimmune diseases, the etiology is multifactorial, with both genetic and environmental factors contributing to it. Case reports of CIDP have found associations with multiple pathogenic organisms including Hepatitis B and C viruses, Bartonella henselae, Mycoplasma pneumoniae, Human immunodeficiency virus, Cytomegalovirus and Epstein-Barr virus. Possible antigenic self-targets include myelin protein 0, myelin protein 2, peripheral myelin protein 22, Connexin 32, and myelin basic protein. Antibodies targeting the Ranvier node proteins such as contactin-1, contactin-associated protein 1, and neurofascin 155 have been described. CIDP is treated with rehabilitation and pharmacological modalities. Pharmacological treatments target autoimmune dysfunction and include corticosteroids, intravenous immunoglobulin, subcutaneous immunoglobulin, plasma exchange, immunosuppressive and immunomodulatory agents such as methotrexate, cyclophosphamide, rituximab, and mycophenolate mofetil. Although there are few observational studies and randomized clinical trials with limited evidence supporting the use of immunosuppressive drugs, they are widely used in clinical practice. A comprehensive review of CIDP is presented herein in light of the autoimmune tautology.
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Autoinmunidad/inmunología , Polirradiculoneuropatía Crónica Inflamatoria Desmielinizante , Corticoesteroides/uso terapéutico , Autoantígenos/inmunología , Femenino , Predisposición Genética a la Enfermedad , Humanos , Inmunoglobulinas Intravenosas/uso terapéutico , Factores Inmunológicos/uso terapéutico , Inmunomodulación/efectos de los fármacos , Inmunosupresores/uso terapéutico , Masculino , Intercambio Plasmático/métodos , Polirradiculoneuropatía Crónica Inflamatoria Desmielinizante/tratamiento farmacológico , Polirradiculoneuropatía Crónica Inflamatoria Desmielinizante/genética , Polirradiculoneuropatía Crónica Inflamatoria Desmielinizante/patologíaRESUMEN
Autoimmune diseases (ADs) are a chronic and clinically heterogeneous group of diseases characterized by share common immunopathogenic mechanisms and risk factors (i.e., the autoimmune tautology), which explain the fact that one AD may coexist with others (i.e., polyautoimmunity - PolyA). In the present exploratory study, a mixed-cluster analysis of the most common autoimmune rheumatic diseases (ARDs) was done. A total of 187 consecutive women with established systemic lupus erythematosus (nâ¯=â¯70), rheumatoid arthritis (nâ¯=â¯51), systemic sclerosis (nâ¯=â¯35) and Sjögren's syndrome (nâ¯=â¯31) were included. A comprehensive clinical, autoantibody and cytokine assessment was simultaneously done. Total PolyA was registered in 142 (75.9%) patients. Six clusters were obtained, built mainly on autoantibodies: PolyA-I to -VI. The PolyA-III cluster showed the highest frequency of overt PolyA (pâ¯=â¯0.01), and the PolyA-I, -III, and -IV clusters exhibited the highest positivity for IL-12/23p40 (pâ¯=â¯0.015). These results provide new insights into the pathophysiology of PolyA and warrant prospective validation to enable development of a more accurate taxonomy of ARDs.
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Artritis Reumatoide/inmunología , Interleucina-12/metabolismo , Lupus Eritematoso Sistémico/inmunología , Esclerodermia Sistémica/inmunología , Síndrome de Sjögren/inmunología , Adulto , Anciano , Artritis Reumatoide/epidemiología , Autoanticuerpos/metabolismo , Autoinmunidad , Análisis por Conglomerados , Estudios de Cohortes , Femenino , Humanos , Lupus Eritematoso Sistémico/epidemiología , Masculino , Persona de Mediana Edad , Esclerodermia Sistémica/epidemiología , Síndrome de Sjögren/epidemiologíaRESUMEN
OBJECTIVES: Resilience, the ability to respond positively to adverse events, may be influenced by long-term stressors and autoimmune/inflammatory conditions such as systemic sclerosis (SSc). Since the immune system plays a role in the development of resilience, we aimed to evaluate the relationship between a panel of cytokines and resilience in patients with SSc. METHODS: Thirty-five consecutive women with established SSc were involved in this exploratory study. Clinical characteristics, including severity of symptoms and resilience, a panel of 15 serum cytokines and 17 autoantibodies were assessed simultaneously. Multivariate methods were used to analyse the data. RESULTS: Interleukin-6 (IL-6) levels were associated with severity of symptoms (ß=1.8395, p=0.04), and low resilience scores (ß= -0.581120, p=0.02). Furthermore, resilience was not associated with clinical manifestations nor polyautoimmunity. Cytokine levels did not significantly differ between groups based on regular physical activity. CONCLUSIONS: The results highlight the importance of IL-6 as a key mediator in the altered cytokine network of SSc.
Asunto(s)
Autoanticuerpos , Interleucina-6 , Esclerodermia Sistémica , Autoanticuerpos/sangre , Autoanticuerpos/inmunología , Citocinas/sangre , Femenino , Humanos , Interleucina-6/sangre , Interleucina-6/fisiología , Esclerodermia Sistémica/sangre , Esclerodermia Sistémica/inmunología , Índice de Severidad de la EnfermedadRESUMEN
PURPOSE OF REVIEW: The autoimmune ecology refers to the interactions between individuals and their environment leading to a breakdown in immune tolerance and, therefore, to the development of one or more autoimmune diseases in such an individual. Herein, an update is offered on four specific factors associated with autoimmune diseases, namely, vitamin D, smoking, alcohol and coffee consumption from the perspective of exposome and metabolomics. RECENT FINDINGS: Smoking is associated with an increased risk for most of the autoimmune diseases. Carbamylation of proteins as well as NETosis have emerged as possible new pathophysiological mechanisms for rheumatoid arthritis. Low-to-moderate alcohol consumption seems to decrease the risk of systemic lupus erythematosus and rheumatoid arthritis, and studies of vitamin have suggested a beneficial effect on these conditions. Coffee intake appears to be a risk factor for type 1 diabetes mellitus and rheumatoid arthritis and a protective factor for multiple sclerosis and primary biliary cholangitis. SUMMARY: Recent studies support the previously established positive associations between environmental factors and most of the autoimmune diseases. Nevertheless, further studies from the perspective of metabolomics, proteomics and genomics will help to clarify the effect of environment on autoimmune diseases.
Asunto(s)
Enfermedades Autoinmunes/inmunología , Enfermedades Autoinmunes/etiología , Enfermedades Autoinmunes/metabolismo , Humanos , Metabolómica , Factores de Riesgo , Fumar/efectos adversosRESUMEN
Molecular mimicry is one of the leading mechanisms by which infectious or chemical agents may induce autoimmunity. It occurs when similarities between foreign and self-peptides favor an activation of autoreactive T or B cells by a foreign-derived antigen in a susceptible individual. However, molecular mimicry is unlikely to be the only underlying mechanism for autoimmune responses; other factors such as breach in central tolerance, non-specific bystander activation, or persistent antigenic stimuli (amongst others) may also contribute to the development of autoimmune diseases. Host genetics, exposure to microbiota and environmental chemicals are additional links to our understanding of molecular mimicry. Our current knowledge of the detailed mechanisms of molecular mimicry is limited by the issues of prolonged periods of latency before the appearance of disease, the lack of enough statistical power in epidemiological studies, the limitations of the potential role of genetics in human studies, the relevance of inbred murine models to the diverse human population and especially the limited technology to systematically dissect the human T-cell repertoire and B-cell responses. Nevertheless, studies on the role of autoreactive T-cells that are generated secondary to molecular mimicry, the diversity of the T-cell receptor repertoires of auto-reactive T-cells, the role of exposure to cryptic antigens, the generation of autoimmune B-cell responses, the interaction of microbiota and chemical adjuvants with the host immune systems all provide clues in advancing our understanding of the molecular mechanisms involved in the evolving concept of molecular mimicry and also may potentially aid in the prevention and treatment of autoimmune diseases.
Asunto(s)
Antígenos Bacterianos/inmunología , Antígenos Virales/inmunología , Autoantígenos/inmunología , Enfermedades Autoinmunes/inmunología , Autoinmunidad , Imitación Molecular/inmunología , Animales , Antígenos Bacterianos/genética , Antígenos Virales/genética , Autoanticuerpos/biosíntesis , Autoantígenos/genética , Enfermedades Autoinmunes/genética , Enfermedades Autoinmunes/microbiología , Enfermedades Autoinmunes/virología , Linfocitos B/inmunología , Reacciones Cruzadas , Expresión Génica , Humanos , Ratones , Receptores de Antígenos de Linfocitos T/genética , Receptores de Antígenos de Linfocitos T/inmunología , Linfocitos T/inmunologíaRESUMEN
PURPOSE: To determine if autonomic symptoms are associated with previous Zika virus infection. METHODS: Case-control study including 35 patients with Zika virus infection without evidence of neurological disease and 105 controls. Symptoms of autonomic dysfunction were assessed with the composite autonomic symptom scale 31 (COMPASS-31). RESULTS: Patients with previous Zika virus infection had significantly higher COMPASS-31 score than controls regardless of age and sex (p = 0.007). The main drivers for the higher scores where orthostatic intolerance (p = 0.003), secretomotor (p = 0.04) and bladder symptoms (p < 0.001). CONCLUSION: Zika virus infection is associated with autonomic dysfunction. The mechanisms remain to be elucidated.