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1.
Rev Alerg Mex ; 69 Suppl 1: s69-s80, 2022.
Artigo em Espanhol | MEDLINE | ID: mdl-34998312

RESUMO

Chronic spontaneous urticaria is a condition that persists for more than six weeks, it occurs in the absence of an identifiable triggering factor and from the pathogenic activation of mast cells and basophils. The possibility of autoimmune etiology in up to 40 % of patients is presented, followed by subclinical infections and psychological factors. Two main mechanisms of the pathogenesis of chronic urticaria have been proposed: the former is the dysregulation of intracellular signaling pathways within mast cells and basophils, which leads to defects in the traffic or function of these cells. The latter is the development of autoantibodies against FcεRIα or IgE, in both mast cells and basophils. Numerous autoimmune diseases such as systemic lupus erythematosus, polymyositis, dermatomyositis, and rheumatoid arthritis have been associated with chronic urticaria; however, autoimmune thyroid disease deserves a special mention. A higher prevalence of antithyroid antibodies has been found, regardless of thyroid function (euthyroidism, hypo and hyperthyroidism) in patients with chronic spontaneous urticaria. Several infections have been linked to chronic urticaria. The best evidence is for Helicobacter pylori infection. Finally, stress is associated with the onset of the disease through the activation of the sympathetic and adrenomedullary system and the hypothalamic-pituitary- adrenal axis. Diagnosis may vary in different regions of the world, but the common feature is the completion of a thorough medical history.


La urticaria crónica espontánea es una afección que persiste durante más de seis semanas y ocurre en ausencia de un factor desencadenante identificable y resulta de la activación patógena de células cebadas y basófilos. Se plantea la posible etiología autoinmune hasta en 40 % de los pacientes, seguida de infecciones subclínicas y factores psicológicos. Se han propuesto dos mecanismos principales de la patogénesis de la urticaria crónica: la desregulación de las vías de señalización intracelular dentro de las células cebadas y basófilos que conduce a defectos en el tráfico o la función de estas células, así como el desarrollo de autoanticuerpos contra FcεRIα o IgE, tanto en células cebadas como en basófilos. Numerosas enfermedades autoinmunes como lupus eritematoso sistémico, polimiositis, dermatomiositis y artritis reumatoide se han asociado a urticaria crónica; sin embargo, la enfermedad tiroidea autoinmune merece una mención especial. Se ha encontrado una mayor prevalencia de anticuerpos antitiroideos, independientemente de la función tiroidea (eutiroidismo, hipo e hipertiroidismo), en pacientes con urticaria crónica espontánea. Varias infecciones se han relacionado a urticaria crónica. Existe la mejor evidencia de infección por Helicobacter pylori. Por último, el estrés está asociado al inicio de la enfermedad mediante la activación del sistema simpático y adrenomedular y el eje hipotálamo hipófisis suprarrenal. El diagnóstico puede variar en las diferentes regiones del mundo, pero el rasgo común es la realización de una historia clínica completa.


Assuntos
Doenças Autoimunes , Urticária Crônica , Infecções por Helicobacter , Helicobacter pylori , Urticária , Autoanticorpos , Doenças Autoimunes/epidemiologia , Autoimunidade , Doença Crônica , Humanos , Imunoglobulina E , Receptores de IgE , Urticária/epidemiologia , Urticária/etiologia
2.
Handb Clin Neurol ; 184: 457-470, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35034754

RESUMO

In recent years, experimental studies have clarified that immune system influences the functioning of the central nervous system (CNS) in both physiologic and pathologic conditions. The neuro-immune crosstalk plays a crucial role in neuronal development and may be critically involved in mediating CNS response to neuronal damage. Multiple sclerosis (MS) represents a good model to investigate how the immune system regulates neuronal activity. Accordingly, a growing body of evidence has demonstrated that increased levels of pro-inflammatory mediators may significantly impact synaptic mechanisms, influencing overall neuronal excitability and synaptic plasticity expression. In this chapter, we provide an overview of preclinical data and clinical studies exploring synaptic functioning noninvasively with transcranial magnetic stimulation (TMS) in patients with MS. Moreover, we examine how inflammation-driven synaptic dysfunction could affect synaptic plasticity expression, negatively influencing the MS course. Contrasting CSF inflammation together with pharmacologic enhancement of synaptic plasticity and application of noninvasive brain stimulation, alone or in combination with rehabilitative treatments, could improve the clinical compensation and prevent the accumulating deterioration in MS.


Assuntos
Esclerose Múltipla , Autoimunidade , Humanos , Inflamação , Plasticidade Neuronal , Estimulação Magnética Transcraniana
3.
J Med Virol ; 94(1): 54-62, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34427929

RESUMO

Coronavirus disease 2019 (COVID-19) is still propagating a year after the start of the pandemic. Besides the complications patients face during the COVID-19 disease period, there is an accumulating body of evidence concerning the late-onset complications of COVID-19, of which autoimmune manifestations have attracted remarkable attention from the first months of the pandemic. Autoimmune hemolytic anemia, immune thrombocytopenic purpura, autoimmune thyroid diseases, Kawasaki disease, Guillain-Barre syndrome, and the detection of autoantibodies are the cues to the discovery of the potential of COVID-19 in inducing autoimmunity. Clarification of the pathophysiology of COVID-19 injuries to the host, whether it is direct viral injury or autoimmunity, could help to develop appropriate treatment.


Assuntos
Doenças Autoimunes/epidemiologia , Doenças Autoimunes/imunologia , Autoimunidade/imunologia , COVID-19/patologia , SARS-CoV-2/imunologia , Autoanticorpos/sangue , Autoanticorpos/imunologia , Doenças Autoimunes/virologia , COVID-19/imunologia , Humanos
4.
Rheum Dis Clin North Am ; 48(1): 371-395, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-34798958

RESUMO

Systemic autoinflammatory diseases (SAIDs) are characterized by unprovoked exaggerated inflammation on a continuum from benign recurrent oral ulceration to life-threatening strokes or amyloidosis, with renal failure as a potential sequela. The ability to discriminate these diagnoses rests on the genetic and mechanistic defect of each disorder, considering potential overlapping autoinflammation, autoimmunity, and immune deficiency. A comprehensive and strategic genetic investigation influences management as well as the consequential expected prognoses in these subsets of rare diseases. The ever-expanding therapeutic armamentarium reflects international collaborations, which will hasten genetic discovery and consensus-driven treatment.


Assuntos
Doenças Hereditárias Autoinflamatórias , Autoimunidade , Doenças Hereditárias Autoinflamatórias/diagnóstico , Doenças Hereditárias Autoinflamatórias/genética , Humanos , Inflamação
5.
Methods Mol Biol ; 2380: 255-265, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-34802137

RESUMO

T follicular helper (Tfh) cells are a subset of specialized CD4+ T cell residing in B cell follicles and confer essential support for germinal center responses, which lead to the generation of long-lived humoral immunity. A great deal of evidence from the past 15 years indicate that excessive differentiation and dysregulated function of Tfh cells often promote autoimmunity by inducing autoantibody production. Interleukin-2 was identified as a major suppressor to inhibit Tfh differentiation. Therefore, IL-2 treatment was applied in suppressing Tfh function in mouse models and more recently in a clinical trial of patients with systemic lupus erythematosus. Here we describe a protocol for low-dose IL-2 treatment in a murine immunization model and on the assessment of the suppression of Tfh response using flow cytometry.


Assuntos
Células T Auxiliares Foliculares , Animais , Autoimunidade , Linfócitos B , Diferenciação Celular , Centro Germinativo , Humanos , Interleucina-2 , Camundongos , Linfócitos T Auxiliares-Indutores
6.
Mol Med ; 27(1): 160, 2021 12 20.
Artigo em Inglês | MEDLINE | ID: mdl-34930107

RESUMO

COVID-19 clinical presentation differs considerably between individuals, ranging from asymptomatic, mild/moderate and severe disease which in some cases are fatal or result in long-term effects. Identifying immune mechanisms behind severe disease development informs screening strategies to predict who are at greater risk of developing life-threatening complications. However, to date clear prognostic indicators of individual risk of severe or long COVID remain elusive. Autoantibodies recognize a range of self-antigens and upon antigen recognition and binding, important processes involved in inflammation, pathogen defence and coagulation are modified. Recent studies report a significantly higher prevalence of autoantibodies that target immunomodulatory proteins including cytokines, chemokines, complement components, and cell surface proteins in COVID-19 patients experiencing severe disease compared to those who experience mild or asymptomatic infections. Here we discuss the diverse impacts of autoantibodies on immune processes and associations with severe COVID-19 disease.


Assuntos
Autoanticorpos/imunologia , Autoanticorpos/metabolismo , COVID-19/complicações , COVID-19/imunologia , SARS-CoV-2/imunologia , Animais , Autoimunidade/fisiologia , COVID-19/metabolismo , Humanos , SARS-CoV-2/metabolismo
7.
Hamostaseologie ; 41(6): 447-457, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34942658

RESUMO

Atherosclerosis is a chronic inflammatory disease of the arterial wall that leads to the build-up of occluding atherosclerotic plaques. Its clinical sequelae, myocardial infarction and stroke, represent the most frequent causes of death worldwide. Atherosclerosis is a multifactorial pathology that involves traditional risk factors and chronic low-grade inflammation in the atherosclerotic plaque and systemically. This process is accompanied by a strong autoimmune response that involves autoreactive T cells in lymph nodes and atherosclerotic plaques, as well as autoantibodies that recognize low-density lipoprotein (LDL) and its main protein component apolipoprotein B (ApoB). In the past 60 years, numerous preclinical observations have suggested that immunomodulatory vaccination with LDL, ApoB, or its peptides has the potential to specifically dampen autoimmunity, enhance tolerance to atherosclerosis-specific antigens, and protect from experimental atherosclerosis in mouse models. Here, we summarize and discuss mechanisms, challenges, and therapeutic opportunities of immunomodulatory vaccination and other strategies to enhance protective immunity in atherosclerosis.


Assuntos
Aterosclerose , Placa Aterosclerótica , Vacinas , Animais , Aterosclerose/prevenção & controle , Autoimunidade , Lipoproteínas LDL , Camundongos
8.
Cells ; 10(12)2021 12 16.
Artigo em Inglês | MEDLINE | ID: mdl-34944064

RESUMO

Stroke remains the number one cause of morbidity in the United States. Within weeks to months after an ischemic event, there is a resolution of inflammation and evidence of neurogenesis; however, years following a stroke, there is evidence of chronic inflammation in the central nervous system, possibly by the persistence of an autoimmune response to brain antigens as a result of ischemia. The mechanisms underlying the involvement of macrophage and microglial activation after stroke are widely acknowledged as having a role in ischemic stroke pathology; thus, modulating inflammation and neurological recovery is a hopeful strategy for treating the long-term outcomes after ischemic injury. Current treatments fail to provide neuroprotective or neurorestorative benefits after stroke; therefore, to ameliorate brain injury-induced deficits, therapies must alter both the initial response to injury and the subsequent inflammatory process. This review will address differences in macrophage and microglia nomenclature and summarize recent work in elucidating the mechanisms of macrophage and microglial participation in antigen presentation, neuroprotection, angiogenesis, neurogenesis, synaptic remodeling, and immune modulating strategies for treating the long-term outcomes after ischemic injury.


Assuntos
Lesões Encefálicas/tratamento farmacológico , Isquemia Encefálica/tratamento farmacológico , Inflamação/tratamento farmacológico , Acidente Vascular Cerebral/tratamento farmacológico , Autoimunidade/genética , Autoimunidade/imunologia , Lesões Encefálicas/imunologia , Lesões Encefálicas/metabolismo , Lesões Encefálicas/patologia , Isquemia Encefálica/imunologia , Isquemia Encefálica/metabolismo , Isquemia Encefálica/patologia , Sistema Nervoso Central/metabolismo , Sistema Nervoso Central/patologia , Humanos , Inflamação/imunologia , Inflamação/metabolismo , Inflamação/patologia , Macrófagos/imunologia , Macrófagos/metabolismo , Macrófagos/patologia , Microglia/imunologia , Microglia/metabolismo , Microglia/patologia , Neurogênese/efeitos dos fármacos , Neurogênese/imunologia , Fármacos Neuroprotetores/uso terapêutico , Acidente Vascular Cerebral/imunologia , Acidente Vascular Cerebral/metabolismo
9.
Science ; 374(6569): 823-824, 2021 11 12.
Artigo em Inglês | MEDLINE | ID: mdl-34762456

RESUMO

[Figure: see text].


Assuntos
Autoimunidade
10.
Scand J Immunol ; 94(5): e13102, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34755902

RESUMO

During COVID-19 infection, reduced function of natural killer (NK) cells can lead to both compromised viral clearance and dysregulation of the immune response. Such dysregulation leads to overproduction of cytokines, a raised neutrophil/lymphocyte ratio and monocytosis. This in turn increases IL-6 expression, which promotes scar and thrombus formation. Excess IL-6 also leads to a further reduction in NK function through downregulation of perforin expression, therefore forming a pathogenic auto-inflammatory feedback loop. The perforin/granzyme system of cytotoxicity is the main mechanism through which NK cells and cytotoxic T lymphocytes eliminate virally infected host cells, as well as being central to their role in regulating immune responses to microbial infection. Here, we present epidemiological evidence suggesting an association between perforin expression and resistance to COVID-19. In addition, we outline the manner in which a pathogenic auto-inflammatory feedback loop could operate and the relationship of this loop to genes associated with severe COVID-19. Such an auto-inflammatory loop may be amenable to synergistic multimodal therapy.


Assuntos
COVID-19/imunologia , Síndrome da Liberação de Citocina/imunologia , Células Matadoras Naturais/imunologia , Linfo-Histiocitose Hemofagocítica/imunologia , Neutrófilos/imunologia , Perforina/metabolismo , SARS-CoV-2/fisiologia , Animais , Autoimunidade/genética , COVID-19/epidemiologia , Síndrome da Liberação de Citocina/epidemiologia , Resistência à Doença , Humanos , Interleucina-6/metabolismo , Linfo-Histiocitose Hemofagocítica/epidemiologia , Perforina/genética
11.
Front Immunol ; 12: 733418, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34603311

RESUMO

Myasthenia gravis (MG) is an autoimmune disease characterized by muscle weakness and abnormal fatigability due to the antibodies against postsynaptic receptors. Despite the individual discrepancy, patients with MG share common muscle weakness, autoimmune dysfunction, and immunosuppressive treatment, which predispose them to infections that can trigger or exacerbate MG. Vaccination, as a mainstay of prophylaxis, is a major management strategy. However, the past years have seen growth in vaccine hesitancy, owing to safety and efficacy concerns. Ironically, vaccines, serving as an essential and effective means of defense, may induce similar immune cross-reactivity to what they are meant to prevent. Herein, we outline the progress in vaccination, review the current status, and postulate the clinical association among MG, vaccination, and immunosuppression. We also address safety and efficacy concerns of vaccination in MG, in relation to COVID-19. Since only a handful of studies have reported vaccination in individuals with MG, we further review the current clinical studies and guidelines in rheumatic diseases. Overall, our reviews offer a reference to guide future vaccine clinical decision-making and improve the management of MG patients.


Assuntos
Vacinas contra COVID-19/efeitos adversos , Vacinas contra COVID-19/imunologia , COVID-19/prevenção & controle , Miastenia Gravis/imunologia , Miastenia Gravis/patologia , SARS-CoV-2/imunologia , Autoimunidade/imunologia , Humanos , Tolerância Imunológica/imunologia , Vacinas contra Influenza/imunologia , Risco , Vacinação/efeitos adversos
12.
Nat Commun ; 12(1): 5911, 2021 10 08.
Artigo em Inglês | MEDLINE | ID: mdl-34625545

RESUMO

Immune cells at sites of inflammation are continuously activated by local antigens and cytokines, and regulatory mechanisms must be enacted to control inflammation. The stepwise hydrolysis of extracellular ATP by ectonucleotidases CD39 and CD73 generates adenosine, a potent immune suppressor. Here we report that human effector CD8 T cells contribute to adenosine production by releasing CD73-containing extracellular vesicles upon activation. These extracellular vesicles have AMPase activity, and the resulting adenosine mediates immune suppression independently of regulatory T cells. In addition, we show that extracellular vesicles isolated from the synovial fluid of patients with juvenile idiopathic arthritis contribute to T cell suppression in a CD73-dependent manner. Our results suggest that the generation of adenosine upon T cell activation is an intrinsic mechanism of human effector T cells that complements regulatory T cell-mediated suppression in the inflamed tissue. Finally, our data underscore the role of immune cell-derived extracellular vesicles in the control of immune responses.


Assuntos
5'-Nucleotidase/metabolismo , Adenosina/metabolismo , Linfócitos T CD8-Positivos/metabolismo , Vesículas Extracelulares/metabolismo , Proteínas Ligadas por GPI/metabolismo , 5'-Nucleotidase/genética , Trifosfato de Adenosina , Animais , Autoimunidade , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD8-Positivos/imunologia , Proliferação de Células , Vesículas Extracelulares/imunologia , Humanos , Inflamação , Ativação Linfocitária , Camundongos , Linfócitos T , Linfócitos T Reguladores/imunologia
13.
Int J Mol Sci ; 22(19)2021 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-34639062

RESUMO

The NOD, LRR, and pyrin domain-containing 3 (NLRP3) protein has been established as a central component of the inflammasome and regulates the inflammatory response to a myriad of environmental, microbial, and endogenous danger stimuli. Assembly of the NLRP3 inflammasome results in the cleavage and activation of caspase-1, in turn causing release of the pro-inflammatory interleukins 1-beta and 18. This activation response, while crucial to coordinated innate immune defense, can be aberrantly activated by the likes of cell-free DNA, and cause significant autoimmune pathology. Complications of autoimmunity induced by aberrant NLRP3 inflammasome activation have a great degree of mechanistic crossover with alloimmune injury in solid organ transplant, and stratagems to neutralize NLRP3 inflammasome activation may prove beneficial in solid organ transplant management. This article reviews NLRP3 inflammasome biology and the pathology associated with its hyperactivation, as well as the connections between NLRP3 inflammasome activation and allograft homeostasis.


Assuntos
Inflamassomos/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Animais , Autoimunidade , DNA/imunologia , Humanos , Neutrófilos/imunologia , Neutrófilos/metabolismo , Neutrófilos/patologia , Especificidade de Órgãos/imunologia , Transplante de Órgãos , Processamento de Proteína Pós-Traducional
14.
Orphanet J Rare Dis ; 16(1): 410, 2021 10 02.
Artigo em Inglês | MEDLINE | ID: mdl-34600590

RESUMO

BACKGROUND: Abnormalities of the immune system are rarely reported in patients affected by RASopathies. Aim of the current study was to investigate the prevalence of immune system dysfunction in a cohort of patients affected by RASopathies. STUDY DESIGN: A group of 69 patients was enrolled: 60 at the Federico II University, Naples, 7 at University Magna Graecia of Catanzaro, 2 at "Scuola Medica Salernitana", Salerno. An age- and sex-matched control group was also enrolled. Autoimmune disorders were investigated according to international consensus criteria. Immune framework was also evaluated by immunoglobulin levels, CD3, CD4, CD8, CD19, CD56 lymphocyte subpopulations, autoantibodies levels and panel of inflammatory molecules, in both patients and controls. RESULTS: Frequent upper respiratory tract infections were recorded in 2 patients; pneumonia, psoriasis and alopecia in single patients. Low IgA levels were detected in 8/44 patients (18.18%), low CD8 T cells in 13/35 patients (37.14%). Anti-tg and anti-TPO antibodies were detected in 3/24 patients (12.5%), anti r-TSH in 2 cases (8.33%), all in euthyroidism. Serum IgA and CD8 levels were significantly lower in patients than in controls (p 0.00685; p 0.000656 respectively). All tested patients showed increased inflammatory molecules compared to controls. These findings may anticipate the detection of overt autoimmune disease. CONCLUSIONS: Patients affected by RASopathies are at risk to develop autoimmune disorders. Routine screening for autoimmunity is recommended in patients with RASopathy.


Assuntos
Doenças Autoimunes , Imunidade Celular , Antígenos CD19 , Autoimunidade , Humanos
15.
Front Endocrinol (Lausanne) ; 12: 746602, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34659128

RESUMO

Background: Some studies have indicated that interferon (IFN) may be valuable in COVID-19. We aimed to evaluate the impact of short-term IFN on incident thyroid dysfunction and autoimmunity among COVID-19 survivors. Methods: We included consecutive adults without known thyroid disorder admitted to Queen Mary Hospital for COVID-19 from July 2020 to January 2021 who had thyroid function tests (TFTs) and anti-thyroid antibodies measured both on admission and at three months. Results: 226 patients were included (median age 55.0 years; 49.6% men): 135 were IFN-treated. There tended to be more abnormal TFTs upon reassessment in IFN-treated patients (8.1% vs 2.2%, p=0.080). 179 patients (65.4% IFN-treated) had a complete reassessment of anti-thyroid antibodies. There were significant increases in titres of both anti-thyroid peroxidase antibodies (anti-TPO: baseline 29.21 units [IQR: 14.97 - 67.14] vs reassessment 34.30 units [IQR: 18.82 - 94.65], p<0.001) and anti-thyroglobulin antibodies (anti-Tg: baseline 8.23 units [IQR: 5.40 - 18.44] vs reassessment 9.14 units [IQR: 6.83 - 17.17], p=0.001) in the IFN-treated group but not IFN-naïve group. IFN treatment (standardised beta 0.245, p=0.001) was independently associated with changes in anti-TPO titre. Of the 143 patients negative for anti-TPO at baseline, 8 became anti-TPO positive upon reassessment (seven IFN-treated; one IFN-naïve). Incident anti-TPO positivity was more likely to be associated with abnormal TFTs upon reassessment (phi 0.188, p=0.025). Conclusion: IFN for COVID-19 was associated with modest increases in anti-thyroid antibody titres, and a trend of more incident anti-TPO positivity and abnormal TFTs during convalescence. Our findings suggest that clinicians monitor the thyroid function and anti-thyroid antibodies among IFN-treated COVID-19 survivors, and call for further follow-up studies regarding the clinical significance of these changes.


Assuntos
Autoimunidade/efeitos dos fármacos , COVID-19/tratamento farmacológico , COVID-19/imunologia , Interferon beta-1b/efeitos adversos , Interferon beta-1b/uso terapêutico , Doenças da Glândula Tireoide/induzido quimicamente , Testes de Função Tireóidea , Glândula Tireoide/efeitos dos fármacos , Adulto , Anticorpos/análise , Estudos de Coortes , Feminino , Seguimentos , Humanos , Imunoglobulinas Glândula Tireoide-Estimulantes/análise , Masculino , Pessoa de Meia-Idade , Sobreviventes , Doenças da Glândula Tireoide/imunologia , Tireotropina/sangue , Tiroxina/sangue , Tri-Iodotironina/sangue
16.
Front Immunol ; 12: 708848, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34659200

RESUMO

Impressive efforts have been made by researchers worldwide in the development of target vaccines against the novel severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and in improving the management of immunomodulating agents. Currently, different vaccine formulations, such as viral vector, mRNA, and protein-based, almost all directed toward the spike protein that includes the domain for receptor binding, have been approved. Although data are not conclusive, patients affected by autoimmune rheumatic diseases (ARDs) seem to have a slightly higher disease prevalence, risk of hospitalization, and death from coronavirus disease-2019 (COVID-19) than the general population. Therefore, ARD patients, under immunosuppressive agents, have been included among the priority target groups for vaccine administration. However, specific cautions are needed to optimize vaccine safety and effectiveness in these patients, such as modification in some of the ongoing immunosuppressive therapies and the preferential use of mRNA other than vector-based vaccines. Immunomodulating agents can be a therapeutic opportunity for the management of COVID-19 patients; however, their clinical impact depends on how they are handled. To place in therapy immunomodulating agents in the correct window of opportunity throughout the identification of surrogate markers of disease progression and host immune response is mandatory to optimize patient's outcome.


Assuntos
Autoimunidade/imunologia , Vacinas contra COVID-19/imunologia , COVID-19/prevenção & controle , Hospedeiro Imunocomprometido/imunologia , Doenças Reumáticas/imunologia , Glicoproteína da Espícula de Coronavírus/imunologia , Humanos , Imunossupressores/efeitos adversos , Imunossupressores/uso terapêutico , Doenças Reumáticas/tratamento farmacológico , SARS-CoV-2/imunologia , Vacinação
17.
Med Hypotheses ; 157: 110702, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34666261

RESUMO

Multiple Sclerosis (MS) is a demyelinating autoimmune disease in which autoreactive T lymphocytes infiltrate the central nervous system (CNS) and react against antigens derived from proteins of the myelin sheath. The reason why T lymphocytes recognize certain myelin antigens as exogenous, activating the autoimmune response, remains unknown and represents the key to understand the pathogenesis of MS. Neurons are characterized by an elevated glycolytic metabolism. Methylglyoxal (MG) is a highly reactive α-oxoaldehyde spontaneously formed as a by-product of glycolysis, and it reacts with proteins, nucleotides and phospholipids forming stable adducts called advanced glycation end-products (AGEs). Several studies demonstrate that MG-derived AGEs accumulate in the plasma and brain of MS patients. Furthermore, there are evidences that post-myelinated oligodendrocytes, the myelin-forming glial cells, increase their glycolytic metabolism to maintain their survival and functions, likely explaining the progressive accumulation of MG in MS lesions. The hypothesis proposed here is that the MG-derived AGEs, accumulated on the proteins composing the myelin sheath, are responsible for the altered antigen presentation process, mimicking exogenous antigens and triggering the autoimmune response. If this hypothesis will be experimentally confirmed a new pathogenic mechanism of MS will be identified.


Assuntos
Esclerose Múltipla , Bainha de Mielina , Antígenos , Autoimunidade , Humanos , Linfócitos T
19.
Bioessays ; 43(12): e2100158, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34677872

RESUMO

Severe COVID-19 is often accompanied by coagulopathies such as thrombocytopenia and abnormal clotting. Rarely, such complications follow SARS-CoV-2 vaccination. The cause of these coagulopathies is unknown. It is hypothesized that coagulopathies accompanying SARS-CoV-2 infections and vaccinations result from bacterial co-infections that synergize with virus-induced autoimmunity due to antigenic mimicry of blood proteins by both bacterial and viral antigens. Coagulopathies occur mainly in severe COVID-19 characterized by bacterial co-infections with Streptococci, Staphylococci, Klebsiella, Escherichia coli, and Acinetobacter baumannii. These bacteria express unusually large numbers of antigens mimicking human blood antigens, as do both SARS-CoV-2 and adenoviruses. Bacteria mimic cardiolipin, prothrombin, albumin, and platelet factor 4 (PF4). SARS-CoV-2 mimics complement factors, Rh antigens, platelet phosphodiesterases, Factors IX and X, von Willebrand Factor (VWF), and VWF protease ADAMTS13. Adenoviruses mimic prothrombin and platelet factor 4. Bacterial prophylaxis, avoidance of vaccinating bacterially infected individuals, and antigen deletion for vaccines may reduce coagulopathy risk. Also see the video abstract here: https://youtu.be/zWDOsghrPg8.


Assuntos
COVID-19 , Coinfecção , Autoanticorpos , Autoimunidade , Bactérias , Vacinas contra COVID-19 , Cardiolipinas , Proteínas de Transporte , Humanos , Fator Plaquetário 4 , Protrombina , SARS-CoV-2
20.
Cells ; 10(10)2021 09 26.
Artigo em Inglês | MEDLINE | ID: mdl-34685525

RESUMO

The coronavirus disease 2019 (COVID-19) is related to enhanced production of NETs, and autoimmune/autoinflammatory phenomena. We evaluated the proportion of low-density granulocytes (LDG) by flow cytometry, and their capacity to produce NETs was compared with that of conventional neutrophils. NETs and their protein cargo were quantified by confocal microscopy and ELISA. Antinuclear antibodies (ANA), anti-neutrophil cytoplasmic antibodies (ANCA) and the degradation capacity of NETs were addressed in serum. MILLIPLEX assay was used to assess the cytokine levels in macrophages' supernatant and serum. We found a higher proportion of LDG in severe and critical COVID-19 which correlated with severity and inflammatory markers. Severe/critical COVID-19 patients had higher plasmatic NE, LL-37 and HMGB1-DNA complexes, whilst ISG-15-DNA complexes were lower in severe patients. Sera from severe/critical COVID-19 patients had lower degradation capacity of NETs, which was reverted after adding hrDNase. Anti-NET antibodies were found in COVID-19, which correlated with ANA and ANCA positivity. NET stimuli enhanced the secretion of cytokines in macrophages. This study unveils the role of COVID-19 NETs as inducers of pro-inflammatory and autoimmune responses. The deficient degradation capacity of NETs may contribute to the accumulation of these structures and anti-NET antibodies are related to the presence of autoantibodies.


Assuntos
Autoimunidade , COVID-19/sangue , COVID-19/imunologia , Armadilhas Extracelulares/imunologia , Imunidade Humoral , Inflamação , Neutrófilos/imunologia , Anticorpos Antinucleares , Peptídeos Catiônicos Antimicrobianos/sangue , Autoanticorpos/metabolismo , Estudos Transversais , Citocinas/metabolismo , Citocinas/farmacologia , Citometria de Fluxo , Granulócitos/metabolismo , Proteína HMGB1/sangue , Voluntários Saudáveis , Humanos , Microscopia Confocal , Monócitos/citologia , Neutrófilos/citologia , SARS-CoV-2 , Ubiquitinas/farmacologia
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