RESUMO
Autoimmunity linked to COVID-19 immunization has been recorded throughout the pandemic. Herein we present six new patients who experienced relapses of previous autoimmune disease (AD) or developed a new autoimmune or autoinflammatory condition following vaccination. In addition, we documented additional cases through a systematic review of the literature up to August 1st, 2022, in which 464 studies (928 cases) were included. The majority of patients (53.6%) were women, with a median age of 48 years (IQR: 34 to 66). The median period between immunization and the start of symptoms was eight days (IQR: 3 to 14). New-onset conditions were observed in 81.5% (n: 756) of the cases. The most common diseases associated with new-onset events following vaccination were immune thrombocytopenia, myocarditis, and Guillain-Barré syndrome. In contrast, immune thrombocytopenia, psoriasis, IgA nephropathy, and systemic lupus erythematosus were the most common illnesses associated with relapsing episodes (18.5%, n: 172). The first dosage was linked with new-onset events (69.8% vs. 59.3%, P = 0.0100), whereas the second dose was related to relapsing disease (29.5% vs. 59.3%, P = 0.0159). New-onset conditions and relapsing diseases were more common in women (51.5% and 62.9%, respectively; P = 0.0081). The groups were evenly balanced in age. No deaths were recorded after the disease relapsed, while 4.7% of patients with new-onset conditions died (P = 0.0013). In conclusion, there may be an association between COVID-19 vaccination and autoimmune and inflammatory diseases. Some ADs seem to be more common than others. Vaccines and SARS-CoV-2 may induce autoimmunity through similar mechanisms. Large, well-controlled studies are warranted to validate this relationship and assess additional variables such as genetic and other environmental factors.
Assuntos
Vacinas contra COVID-19 , COVID-19 , Doenças do Sistema Imunitário , Púrpura Trombocitopênica Idiopática , Trombocitopenia , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , COVID-19/epidemiologia , COVID-19/prevenção & controle , Vacinas contra COVID-19/efeitos adversos , Púrpura Trombocitopênica Idiopática/epidemiologia , Púrpura Trombocitopênica Idiopática/etiologia , SARS-CoV-2 , Vacinação/efeitos adversosRESUMO
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.
Assuntos
Doenças Autoimunes/imunologia , Betacoronavirus/imunologia , Infecções por Coronavirus/imunologia , Síndrome da Liberação de Citocina/imunologia , Pneumonia Viral/imunologia , Imunidade Adaptativa/genética , Doenças Autoimunes/diagnóstico , Doenças Autoimunes/terapia , Doenças Autoimunes/virologia , Betacoronavirus/isolamento & purificação , COVID-19 , Teste para COVID-19 , Técnicas de Laboratório Clínico , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/terapia , Estado Terminal , Síndrome da Liberação de Citocina/diagnóstico , Síndrome da Liberação de Citocina/terapia , Síndrome da Liberação de Citocina/virologia , Feminino , Predisposição Genética para Doença , Humanos , Imunidade Inata/genética , Imunização Passiva/métodos , Mediadores da Inflamação/sangue , Mediadores da Inflamação/imunologia , Ativação de Macrófagos/genética , Ativação de Macrófagos/imunologia , Masculino , Pandemias , Pneumonia Viral/diagnóstico , Pneumonia Viral/epidemiologia , Pneumonia Viral/terapia , Fatores de Risco , SARS-CoV-2 , Índice de Gravidade de Doença , Fatores Sexuais , Soroterapia para COVID-19RESUMO
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.
Assuntos
Ebolavirus/imunologia , Doença pelo Vírus Ebola/imunologia , Doença pelo Vírus Ebola/virologia , Animais , Anticorpos Antivirais/imunologia , Autoanticorpos/imunologia , Diabetes Mellitus Tipo 1/imunologia , Diabetes Mellitus Tipo 1/virologia , HumanosRESUMO
The interaction over time of genetic, epigenetic and environmental factors (i.e., autoimmune ecology) increases or decreases the liability an individual would have to develop an autoimmune disease (AD) depending on the misbalance between risk and protective effects. Pathogens have been the most common antecedent events studied, but multiple other environmental factors including xenobiotic chemicals, drugs, vaccines, and nutritional factors have been implicated into the development of ADs. Three main mechanisms have been offered to explain the development of autoimmunity: molecular mimicry, epitope spreading, and bystander activation. The latter is characterized by auto-reactive B and T cells that undergo activation in an antigen-independent manner, influencing the development and course of autoimmunity. Activation occurs due to a combination of an inflammatory milieu, co-signaling ligands, and interactions with neighboring cells. In this review, we will discuss the studies performed seeking to define the role of bystander activation in systemic and organ-specific ADs. In all cases, we are cognizant of individual differences between hosts and the variable latency time for clinical expression of disease, all of which have made our understanding of the etiology of loss of immune tolerance difficult and enigmatic.
Assuntos
Doenças Autoimunes/imunologia , Efeito Espectador/imunologia , Linfócitos T/imunologia , Xenobióticos/efeitos adversos , Animais , Doenças Autoimunes/etiologia , Autoimunidade , Interação Gene-Ambiente , Humanos , Tolerância Imunológica , IndividualidadeRESUMO
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.
Assuntos
Autoimunidade/imunologia , Polirradiculoneuropatia Desmielinizante Inflamatória Crônica , Corticosteroides/uso terapêutico , Autoantígenos/imunologia , Feminino , Predisposição Genética para Doença , Humanos , Imunoglobulinas Intravenosas/uso terapêutico , Fatores Imunológicos/uso terapêutico , Imunomodulação/efeitos dos fármacos , Imunossupressores/uso terapêutico , Masculino , Troca Plasmática/métodos , Polirradiculoneuropatia Desmielinizante Inflamatória Crônica/tratamento farmacológico , Polirradiculoneuropatia Desmielinizante Inflamatória Crônica/genética , Polirradiculoneuropatia Desmielinizante Inflamatória Crônica/patologiaRESUMO
The primary immunodeficiency diseases (PIDs) include many genetic disorders that affect different components of the innate and adaptive responses. The number of distinct genetic PIDs has increased exponentially with improved methods of detection and advanced laboratory methodology. Patients with PIDs have an increased susceptibility to infectious diseases and non-infectious complications including allergies, malignancies and autoimmune diseases (ADs), the latter being the first manifestation of PIDs in several cases. There are two types of PIDS. Monogenic immunodeficiencies due to mutations in genes involved in immunological tolerance that increase the predisposition to develop autoimmunity including polyautoimmunity, and polygenic immunodeficiencies characterized by a heterogeneous clinical presentation that can be explained by a complex pathophysiology and which may have a multifactorial etiology. The high prevalence of ADs in PIDs demonstrates the intricate relationships between the mechanisms of these two conditions. Defects in central and peripheral tolerance, including mutations in AIRE and T regulatory cells respectively, are thought to be crucial in the development of ADs in these patients. In fact, pathology that leads to PID often also impacts the Treg/Th17 balance that may ease the appearance of a proinflammatory environment, increasing the odds for the development of autoimmunity. Furthermore, the influence of chronic and recurrent infections through molecular mimicry, bystander activation and super antigens activation are supposed to be pivotal for the development of autoimmunity. These multiple mechanisms are associated with diverse clinical subphenotypes that hinders an accurate diagnosis in clinical settings, and in some cases, may delay the selection of suitable pharmacological therapies. Herein, a comprehensively appraisal of the common mechanisms among these conditions, together with clinical pearls for treatment and diagnosis is presented.
Assuntos
Autoimunidade , Doenças da Imunodeficiência Primária/etiologia , Doenças Autoimunes/diagnóstico , Doenças Autoimunes/etiologia , Doenças Autoimunes/metabolismo , Doenças Autoimunes/terapia , Gerenciamento Clínico , Suscetibilidade a Doenças/imunologia , Epitopos/imunologia , Humanos , Tolerância Imunológica , Síndromes de Imunodeficiência/diagnóstico , Síndromes de Imunodeficiência/etiologia , Síndromes de Imunodeficiência/metabolismo , Infecções/complicações , Mimetismo Molecular , Doenças da Imunodeficiência Primária/diagnóstico , Doenças da Imunodeficiência Primária/metabolismo , Doenças da Imunodeficiência Primária/terapia , Subpopulações de Linfócitos T/imunologia , Subpopulações de Linfócitos T/metabolismoRESUMO
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.
Assuntos
Antígenos de Bactérias/imunologia , Antígenos Virais/imunologia , Autoantígenos/imunologia , Doenças Autoimunes/imunologia , Autoimunidade , Mimetismo Molecular/imunologia , Animais , Antígenos de Bactérias/genética , Antígenos Virais/genética , Autoanticorpos/biossíntese , Autoantígenos/genética , Doenças Autoimunes/genética , Doenças Autoimunes/microbiologia , Doenças Autoimunes/virologia , Linfócitos B/imunologia , Reações Cruzadas , Expressão Gênica , Humanos , Camundongos , Receptores de Antígenos de Linfócitos T/genética , Receptores de Antígenos de Linfócitos T/imunologia , Linfócitos T/imunologiaRESUMO
INTRODUCTION: Guillain-Barré syndrome is the most common cause of acute flaccid paralysis worldwide. Microorganisms such as Campylobacter jejuni, Cytomegalovirus, Epstein-Barr virus, Mycoplasma pneumoniae, Haemophilus influenzae and Zika virus have been linked to the disease. The most common clinical variants are acute inflammatory demyelinating polyneuropathy and acute motor axonal neuropathy. Plasma exchange and intravenous immunoglobulins are the standard therapy for the disease. AREAS COVERED: Research to elucidate the pathophysiology of Guillain-Barré syndrome has led to the development of drugs directed towards new potential therapeutic targets. This review offers a comprehensive view of the current treatment based upon the physiopathology. EXPERT OPINION: Patients with Guillain-Barré syndrome need a multidisciplinary approach, limitation to walk unaided and disability score are indicators for treatment as well as the presence of autonomic dysfunction and pain. Admission to intensive care units should be considered for those patients presenting with respiratory failure, bulbar involvement and progression of the disease. Research aimed to deciphering the pathophysiology of the disease, discovering new biomarkers and establishing algorithms of prediction of both the disease and its outcomes is warranted.
Assuntos
Síndrome de Guillain-Barré/terapia , Imunoterapia/métodos , Progressão da Doença , Síndrome de Guillain-Barré/imunologia , Humanos , Imunoglobulinas Intravenosas/uso terapêutico , Fatores Imunológicos/uso terapêutico , Imunoterapia/efeitos adversos , Troca Plasmática/métodos , Plasmaferese/métodosRESUMO
Guillain-Barré syndrome (GBS) and transverse myelitis (TM) both represent immunologically mediated polyneuropathies of major clinical importance. Both are thought to have a genetic predisposition, but as of yet no specific genetic risk loci have been clearly defined. Both are considered autoimmune, but again the etiologies remain enigmatic. Both may be induced via molecular mimicry, particularly from infectious agents and vaccines, but clearly host factor and co-founding host responses will modulate disease susceptibility and natural history. GBS is an acute inflammatory immune-mediated polyradiculoneuropathy characterized by tingling, progressive weakness, autonomic dysfunction, and pain. Immune injury specifically takes place at the myelin sheath and related Schwann-cell components in acute inflammatory demyelinating polyneuropathy, whereas in acute motor axonal neuropathy membranes on the nerve axon (the axolemma) are the primary target for immune-related injury. Outbreaks of GBS have been reported, most frequently related to Campylobacter jejuni infection, however, other agents such as Zika Virus have been strongly associated. Patients with GBS related to infections frequently produce antibodies against human peripheral nerve gangliosides. In contrast, TM is an inflammatory disorder characterized by acute or subacute motor, sensory, and autonomic spinal cord dysfunction. There is interruption of ascending and descending neuroanatomical pathways on the transverse plane of the spinal cord similar to GBS. It has been suggested to be triggered by infectious agents and molecular mimicry. In this review, we will focus on the putative role of infectious agents as triggering factors of GBS and TM.
Assuntos
Doenças Transmissíveis/patologia , Síndrome de Guillain-Barré/patologia , Mielite Transversa/patologia , Doenças Transmissíveis/imunologia , Doenças Transmissíveis/microbiologia , Doenças Transmissíveis/virologia , Síndrome de Guillain-Barré/imunologia , Síndrome de Guillain-Barré/microbiologia , Síndrome de Guillain-Barré/virologia , Humanos , Imunidade , Mielite Transversa/imunologia , Mielite Transversa/microbiologia , Mielite Transversa/virologiaRESUMO
Tick-borne diseases (TBDs) are emerging and reemerging diseases transmitted by ticks, which portray wide heterogeneity and global distribution. TBDs may present acute clinical pictures that resemble those of autoimmune diseases (i.e., musculoskeletal symptoms, cutaneous involvement, neurologic impairment, renal failure, etc.), and in some cases infection is considered a triggering factor for autoimmunity (e.g., rheumatoid arthritis, autoimmune thyroid disease, vasculitides). The clinician should consider TBDs among the differential diagnoses when approaching autoimmune-like signs in areas of tick infestation. Epidemiological setting (e.g., endemic areas, seasons) and an accurate diagnostic approach (i.e., clinical history, physical examination and laboratory tests) are necessary to confirm TBDs. Further, control and prevention of TBDs is warranted. Research in the fields of ticks microbiome and vaccination (i.e., wildlife and humans) are ahead to control vector transmission and bacterial infection. This review offers a comprehensive update on TBDs and their relationship with autoimmunity.