Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 11.647
Filtrar
1.
Clin Immunol ; 230: 108817, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34352391

RESUMO

Many studies have analyzed myelin-reactivity of T cells in multiple sclerosis (MS); however, with conflicting results. In this study we compare methods to determine myelin reactivity of T cells and aim to delineate the cause of inconsistency in the literature. Challenging T cells with myelin antigens we found a significant increase in antigen-reactivity of T cells from patients with MS using an ELISpot-assay, in contrast to a CFSE-dilution assay. Comparing the two assays showed that the myelin-reactive T cells detected in the ELISpot-assay originated primarily from effector memory T cells in contrast to the myelin-reactive T cells of the CFSE-assay representing a population of both naïve, central memory and effector memory T cells. This diversity in T cell populations activated in the two assays likely contribute to the discrepancy found in the literature and encourages thorough considerations when choosing an assay to determine antigen-specificity of T cells in future studies.


Assuntos
Imunoensaio/métodos , Esclerose Múltipla Recidivante-Remitente/imunologia , Proteínas da Mielina/imunologia , Linfócitos T/imunologia , Adulto , Autoantígenos/imunologia , Estudos de Casos e Controles , ELISPOT , Feminino , Fluoresceínas , Corantes Fluorescentes , Humanos , Memória Imunológica , Masculino , Pessoa de Meia-Idade , Proteína Básica da Mielina/imunologia , Glicoproteína Mielina-Oligodendrócito/imunologia , Succinimidas , Linfócitos T/classificação , Adulto Jovem
2.
Int J Mol Sci ; 22(16)2021 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-34445670

RESUMO

While first and foremost considered a respiratory infection, COVID-19 can result in complications affecting multiple organs. Immune responses in COVID-19 can both protect against the disease as well as drive it. Insights into these responses, and specifically the targets being recognised by the immune system, are of vital importance in understanding the side effects of COVID-19 and associated pathologies. The body's adaptive immunity recognises and responds against specific targets (antigens) expressed by foreign pathogens, but not usually to target self-antigens. However, if the immune system becomes dysfunctional, adaptive immune cells can react to self-antigens, which can result in autoimmune disease. Viral infections are well reported to be associated with, or exacerbate, autoimmune diseases such as multiple sclerosis (MS) and systemic lupus erythematosus (SLE). In COVID-19 patients, both new onset MS and SLE, as well as the occurrence of other autoimmune-like pathologies, have been reported. Additionally, the presence of autoantibodies, both with and without known associations to autoimmune diseases, have been found. Herein we describe the mechanisms of virally induced autoimmunity and summarise some of the emerging reports on the autoimmune-like diseases and autoreactivity that is reported to be associated with SARS-CoV-2 infection.


Assuntos
Doenças Autoimunes/imunologia , Doenças Autoimunes/virologia , COVID-19/imunologia , Imunidade Adaptativa , Artrite Reumatoide/imunologia , Autoanticorpos/imunologia , Autoantígenos/imunologia , Autoimunidade , COVID-19/virologia , Humanos , Lúpus Eritematoso Sistêmico/imunologia , SARS-CoV-2/imunologia
3.
Int J Mol Sci ; 22(15)2021 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-34361054

RESUMO

We addressed the issue of C1q autoantigenicity by studying the structural features of the autoepitopes recognized by the polyclonal anti-C1q antibodies present in Lupus Nephritis (LN) sera. We used six fractions of anti-C1q as antigens and selected anti-idiotypic scFv antibodies from the phage library "Griffin.1". The monoclonal scFv A1 was the most potent inhibitor of the recognition of C1q and its fragments ghA, ghB and ghC, comprising the globular domain gC1q, by the lupus autoantibodies. It was sequenced and in silico folded by molecular dynamics into a 3D structure. The generated 3D model of A1 elucidated CDR similarity to the apical region of gC1q, thus mapping indirectly for the first time a globular autoepitope of C1q. The VH CDR2 of A1 mimicked the ghA sequence GSEAD suggested as a cross-epitope between anti-DNA and anti-C1q antibodies. Other potential inhibitors of the recognition of C1q by the LN autoantibodies among the selected recombinant antibodies were the monoclonal scFv F6, F9 and A12.


Assuntos
Anticorpos Anti-Idiotípicos/imunologia , Autoanticorpos/sangue , Autoantígenos/imunologia , Complemento C1q/imunologia , Epitopos/imunologia , Nefrite Lúpica/imunologia , Anticorpos de Cadeia Única/imunologia , Humanos , Nefrite Lúpica/sangue , Estrutura Terciária de Proteína , Subunidades Proteicas
4.
Clin Neurol Neurosurg ; 208: 106834, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34329810

RESUMO

Several neurological presentations have been reported following coronavirus 2019 (COVID-19) infection. This case report describes three myasthenia gravis (MG) patients presented following COVID-19 infection. We report three adult patients with myasthenic Gravis and COVID-19 infection. The patients are between 38 and 61 years old. Case 1 is a 61-year-old woman with progressive dysphagia, nasal speech, ocular ptosis, diplopia, and proximal muscle weakness for 10 days. She had a COVID-19 infection 6 weeks ago. Case 2 is a 57-year-old man with clinical symptoms of muscular fatigability, diplopia, ptosis, and dysphagia for a week and a positive COVID-19 infection 10 days ago. Case 3 is a 38-year-old woman with fatigability, ptosis, dysphagia, and a diagnosis of COVID-19 infection 4 weeks ago. All patients had a positive RT-PCR for COVID-19 infection by nasopharyngeal swab test and a high-level acetylcholine receptor antibody in the serum. All patients were treated with pyridostigmine and prednisolone with a favorable outcome. MG may appear following COVID-19 infection, and the role of molecular mimicry and latent MG activation should be considered the cause of the disease onset.


Assuntos
COVID-19/complicações , Miastenia Gravis/virologia , Adulto , Anti-Inflamatórios/uso terapêutico , Autoanticorpos/sangue , Autoanticorpos/imunologia , Autoantígenos/imunologia , COVID-19/imunologia , Inibidores da Colinesterase/uso terapêutico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Miastenia Gravis/tratamento farmacológico , Miastenia Gravis/imunologia , Prednisolona/uso terapêutico , Receptores Colinérgicos/imunologia , SARS-CoV-2/imunologia
5.
J Autoimmun ; 123: 102706, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34293683

RESUMO

Autoimmune phenomena and clinically apparent autoimmune diseases, including autoimmune hepatitis, are increasingly been reported not only after natural infection with the SARS-CoV-2 virus, but also after vaccination against it. We report the case of a 63-year old man without a history of autoimmunity or SARS-CoV-2 natural infection who experienced acute severe autoimmune-like hepatitis seven days after the first dose of the mRNA-1273 SARS-CoV-2 vaccine. Liver histology showed inflammatory portal infiltrate with interface hepatitis, lobular and centrilobular inflammation with centrilobular necrosis, in absence of fibrosis and steatosis. Serum immunoglobulin G was slightly elevated. Autoimmune liver serology showed an indirect immunofluorescence pattern on triple rodent tissue compatible with anti-mitochondrial antibody (AMA), but, unexpectedly, this pattern was not mirrored by positivity for primary biliary cholangitis (PBC)-specific molecular tests, indicating that this antibody is different from classical AMA. Anti-nuclear antibody (ANA) was also positive with a rim-like indirect immunofluorescence pattern on liver and HEp2 cell substrates, similar to PBC-specific ANA; however, anti-gp210 and a large panel of molecular-based assays for nuclear antigens were negative, suggesting a unique ANA in our patient. He carries the HLA DRB1*11:01 allele, which is protective against PBC. Response to prednisone treatment was satisfactory. The clinical significance of these novel specificities needs to be further evaluated in this emerging condition.


Assuntos
Autoanticorpos/imunologia , Vacinas contra COVID-19/efeitos adversos , COVID-19/prevenção & controle , Cadeias HLA-DRB1/imunologia , Hepatite Autoimune/etiologia , Mitocôndrias/imunologia , SARS-CoV-2/imunologia , Vacinação/efeitos adversos , Animais , Anticorpos Antinucleares/imunologia , Especificidade de Anticorpos , Autoantígenos/imunologia , Linhagem Celular , Técnica Indireta de Fluorescência para Anticorpo , Hepatite Autoimune/tratamento farmacológico , Hepatite Autoimune/imunologia , Hepatite Autoimune/patologia , Humanos , Imunossupressores/uso terapêutico , Fígado/imunologia , Fígado/patologia , Masculino , Pessoa de Meia-Idade , Prednisona/uso terapêutico , Rosuvastatina Cálcica/efeitos adversos , Rosuvastatina Cálcica/uso terapêutico
6.
J Autoimmun ; 122: 102682, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34214763

RESUMO

The variability in resolution of SARS-CoV-2-infections between individuals neither is comprehended, nor are the long-term immunological consequences. To assess the long-term impact of a SARS-CoV-2-infection on the immune system, we conducted a prospective study of 80 acute and former SARS-CoV-2 infected individuals and 39 unexposed donors to evaluate autoantibody responses and immune composition. Autoantibody levels against cyclic citrullinated peptide (CCP), a specific predictor for rheumatoid arthritis (RA), were significantly (p = 0.035) elevated in convalescents only, whereas both acute COVID-19 patients and long-term convalescents showed critically increased levels of anti-tissue transglutaminase (TG), a specific predictor of celiac disease (CD) (p = 0.002). Both, anti-CCP and anti-TG antibody levels were still detectable after 4-8 months post infection. Anti-TG antibodies occurred predominantly in aged patients in a context of a post-SARS-CoV-2-specific immune composition (R2 = 0.31; p = 0.044). This study shows that increased anti-CCP and anti-TG autoantibody levels can remain long-term after recovering even from mildly experienced COVID-19. The inter-relationship of the lung as viral entry side and RA- and CD-associated autoimmunity indicates that a SARS-CoV-2-infection could be a relevant environmental factor in their pathogenesis.


Assuntos
Autoanticorpos/sangue , COVID-19/imunologia , Peptídeos Cíclicos/imunologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Anti-Proteína Citrulinada/sangue , Anticorpos Anti-Proteína Citrulinada/imunologia , Artrite Reumatoide/imunologia , Autoanticorpos/imunologia , Autoantígenos/imunologia , Doença Celíaca/imunologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Estudos Prospectivos , SARS-CoV-2 , Transglutaminases/imunologia , Adulto Jovem
7.
Am J Pathol ; 191(8): 1474-1486, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34294193

RESUMO

Humans cannot synthesize the common mammalian sialic acid N-glycolylneuraminic acid (Neu5Gc) because of an inactivating deletion in the cytidine-5'-monophospho-(CMP)-N-acetylneuraminic acid hydroxylase (CMAH) gene responsible for its synthesis. Human Neu5Gc deficiency can lead to development of anti-Neu5Gc serum antibodies, the levels of which can be affected by Neu5Gc-containing diets and by disease. Metabolic incorporation of dietary Neu5Gc into human tissues in the face of circulating antibodies against Neu5Gc-bearing glycans is thought to exacerbate inflammation-driven diseases like cancer and atherosclerosis. Probing of sera with sialoglycan arrays indicated that patients with Duchenne muscular dystrophy (DMD) had a threefold increase in overall anti-Neu5Gc antibody titer compared with age-matched controls. These antibodies recognized a broad spectrum of Neu5Gc-containing glycans. Human-like inactivation of the Cmah gene in mice is known to modulate severity in a variety of mouse models of human disease, including the X chromosome-linked muscular dystrophy (mdx) model for DMD. Cmah-/-mdx mice can be induced to develop anti-Neu5Gc-glycan antibodies as humans do. The presence of anti-Neu5Gc antibodies, in concert with induced Neu5Gc expression, correlated with increased severity of disease pathology in Cmah-/-mdx mice, including increased muscle fibrosis, expression of inflammatory markers in the heart, and decreased survival. These studies suggest that patients with DMD who harbor anti-Neu5Gc serum antibodies might exacerbate disease severity when they ingest Neu5Gc-rich foods, like red meats.


Assuntos
Autoanticorpos/sangue , Distrofia Muscular de Duchenne/imunologia , Distrofia Muscular de Duchenne/patologia , Ácidos Neuramínicos/sangue , Ácidos Neuramínicos/imunologia , Animais , Autoanticorpos/imunologia , Autoantígenos/imunologia , Criança , Modelos Animais de Doenças , Humanos , Masculino , Camundongos , Camundongos Endogâmicos mdx , Camundongos Knockout , Distrofia Muscular de Duchenne/sangue
8.
Mol Immunol ; 137: 105-113, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34242919

RESUMO

Underlying mechanisms of multi-organ manifestations and exacerbated inflammation in COVID-19 are yet to be delineated. The hypothesis of SARS-CoV-2 triggering autoimmunity is gaining attention and, in the present study, we have identified 28 human proteins harbouring regions homologous to SARS-CoV-2 peptides that could possibly be acting as autoantigens in COVID-19 patients displaying autoimmune conditions. Interestingly, these conserved regions are amongst the experimentally validated B cell epitopes of SARS-CoV-2 proteins. The reported human proteins have demonstrated presence of autoantibodies against them in typical autoimmune conditions which may explain the frequent occurrence of autoimmune conditions following SARS-CoV-2 infection. Moreover, the proposed autoantigens' widespread tissue distribution is suggestive of their involvement in multi-organ manifestations via molecular mimicry. We opine that our report may aid in directing subsequent necessary antigen-specific studies, results of which would be of long-term relevance in management of extrapulmonary symptoms of COVID-19.


Assuntos
Autoantígenos/imunologia , Doenças Autoimunes/complicações , COVID-19/etiologia , Epitopos de Linfócito B/imunologia , SARS-CoV-2/imunologia , Autoanticorpos/imunologia , Doenças Autoimunes/imunologia , Doenças Autoimunes/virologia , Autoimunidade/imunologia , COVID-19/imunologia , COVID-19/patologia , Humanos , Mimetismo Molecular/imunologia
9.
Circulation ; 144(6): 471-484, 2021 08 10.
Artigo em Inglês | MEDLINE | ID: mdl-34281357

RESUMO

Myocarditis has been recognized as a rare complication of coronavirus disease 2019 (COVID-19) mRNA vaccinations, especially in young adult and adolescent males. According to the US Centers for Disease Control and Prevention, myocarditis/pericarditis rates are ≈12.6 cases per million doses of second-dose mRNA vaccine among individuals 12 to 39 years of age. In reported cases, patients with myocarditis invariably presented with chest pain, usually 2 to 3 days after a second dose of mRNA vaccination, and had elevated cardiac troponin levels. ECG was abnormal with ST elevations in most, and cardiac MRI was suggestive of myocarditis in all tested patients. There was no evidence of acute COVID-19 or other viral infections. In 1 case, a cardiomyopathy gene panel was negative, but autoantibody levels against certain self-antigens and frequency of natural killer cells were increased. Although the mechanisms for development of myocarditis are not clear, molecular mimicry between the spike protein of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and self-antigens, trigger of preexisting dysregulated immune pathways in certain individuals, immune response to mRNA, and activation of immunologic pathways, and dysregulated cytokine expression have been proposed. The reasons for male predominance in myocarditis cases are unknown, but possible explanations relate to sex hormone differences in immune response and myocarditis, and also underdiagnosis of cardiac disease in women. Almost all patients had resolution of symptoms and signs and improvement in diagnostic markers and imaging with or without treatment. Despite rare cases of myocarditis, the benefit-risk assessment for COVID-19 vaccination shows a favorable balance for all age and sex groups; therefore, COVID-19 vaccination is recommended for everyone ≥12 years of age.


Assuntos
Autoantígenos/imunologia , Vacinas contra COVID-19/efeitos adversos , COVID-19/prevenção & controle , Miocardite/induzido quimicamente , SARS-CoV-2/imunologia , Glicoproteína da Espícula de Coronavírus/imunologia , Biomarcadores , COVID-19/epidemiologia , COVID-19/imunologia , Vacinas contra COVID-19/imunologia , Vacinas contra COVID-19/uso terapêutico , Feminino , Humanos , Masculino , Mimetismo Molecular/imunologia , Miocardite/imunologia , Fatores Sexuais
10.
Front Immunol ; 12: 646894, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34177895

RESUMO

The origin and the global spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causing coronavirus disease 2019 (COVID-19) in early 2020 was accompanied by high rates of mortality in regions belonging to the ancient silk road, such as the south of China, Iran, Turkey and the northern parts of Italy. However, children seem to be spared in the epidemic as very small percentage worldwide being ill. The protection of children and neonates suggests the involvement of a specific component of adaptive immunity present at early development. Native immunoglobulin belonging to the class of IgM is abundantly present in neonates and children and is known for its recognition of self- and altered self-antigens. Native IgM may be able to neutralize virus by the recognition of endogenous "danger signal" encoded in the viral envelope and originally imprinted in the membranes of infected and stressed cells. Noteworthy, thrombosis and vasculitis, two symptoms in severely affected adult and pediatric patients are shared between COVID-19 and patients with Behcet's disease, an autoimmune disorder exhibiting a region-specific prevalence in countries of the former silk road. Molecular mechanisms and clinical indicators suggest reactive oxygen species as trigger factor for severe progression of COVID-19 and establish a link to the innate immune defense against bacteria. The selective pressure exerted by bacterial pathogens may have shaped the genetics of inhabitants at this ancient trade route in favor of bacterial defense, to the detriment of severe COVID-19 progression in the 21th century.


Assuntos
Linfócitos B/imunologia , COVID-19/imunologia , Modelos Imunológicos , SARS-CoV-2/fisiologia , Adulto , Enzima de Conversão de Angiotensina 2/metabolismo , Autoantígenos/imunologia , COVID-19/epidemiologia , Criança , Suscetibilidade a Doenças , Humanos , Imunoglobulina M/metabolismo , Padrões Moleculares Associados a Patógenos/imunologia , Prevalência , Risco , Fatores Socioeconômicos
11.
Clin Immunol ; 229: 108774, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34111525

RESUMO

Systemic sclerosis (SSc) is associated, in nearly all patients, with autoantibodies (Ab). Accordingly, and in order to identify major (anti-CEN A/B and anti-Topo I) but also minor Abs, the usefulness of combining indirect immunofluorescence (IIF) on HEp-2 cells with an 11 multi-antigenic SSc immunodot was explored. 1689 samples tested at the request of clinicians, were evaluated retrospectively. The positivity rate was 28.8% and the diagnosis of SSc was supported for 232 samples. Two groups of Abs were considered: group 1, Abs (anti-CENP A/B, anti-Topo I) present at elevated levels in SSc patients; group 2, Abs for which the Ab specificity (odds ratio and/or positive predictive value) was improved by using IIF on HEp-2 cells (RNA-Polymerase III, fibrillarin, Th/T0, PM-Scl). Altogether, this study highlights the utility of combining IIF on HEp-2 cells with the SSc immunodot as the first line of an SSc Abs detection/SSc diagnostic strategy.


Assuntos
Autoanticorpos/sangue , Técnica Indireta de Fluorescência para Anticorpo/métodos , Immunoblotting/métodos , Escleroderma Sistêmico/diagnóstico , Escleroderma Sistêmico/imunologia , Adulto , Idoso , Autoantígenos/imunologia , Linhagem Celular , Proteína Centromérica A/imunologia , Proteína B de Centrômero/imunologia , DNA Topoisomerases Tipo I/imunologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
12.
J Autoimmun ; 122: 102683, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34144328

RESUMO

The renin-angiotensin system (RAS) plays a major role in COVID-19. Severity of several inflammation-related diseases has been associated with autoantibodies against RAS, particularly agonistic autoantibodies for angiotensin type-1 receptors (AA-AT1) and autoantibodies against ACE2 (AA-ACE2). Disease severity of COVID-19 patients was defined as mild, moderate or severe following the WHO Clinical Progression Scale and determined at medical discharge. Serum AA-AT1 and AA-ACE2 were measured in COVID-19 patients (n = 119) and non-infected controls (n = 23) using specific solid-phase, sandwich enzyme-linked immunosorbent assays. Serum LIGHT (TNFSF14; tumor necrosis factor ligand superfamily member 14) levels were measured with the corresponding assay kit. At diagnosis, AA-AT1 and AA-ACE2 levels were significantly higher in the COVID-19 group relative to controls, and we observed significant association between disease outcome and serum AA-AT1 and AA-ACE2 levels. Mild disease patients had significantly lower levels of AA-AT1 (p < 0.01) and AA-ACE2 (p < 0.001) than moderate and severe patients. No significant differences were detected between males and females. The increase in autoantibodies was not related to comorbidities potentially affecting COVID-19 severity. There was significant positive correlation between serum levels of AA-AT1 and LIGHT (TNFSF14; rPearson = 0.70, p < 0.001). Both AA-AT1 (by agonistic stimulation of AT1 receptors) and AA-ACE2 (by reducing conversion of Angiotensin II into Angiotensin 1-7) may lead to increase in AT1 receptor activity, enhance proinflammatory responses and severity of COVID-19 outcome. Patients with high levels of autoantibodies require more cautious control after diagnosis. Additionally, the results encourage further studies on the possible protective treatment with AT1 receptor blockers in COVID-19.


Assuntos
Enzima de Conversão de Angiotensina 2/imunologia , Autoanticorpos/sangue , Autoantígenos/imunologia , COVID-19/imunologia , Receptor Tipo 1 de Angiotensina/imunologia , Idoso , Autoanticorpos/imunologia , COVID-19/sangue , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Sistema Renina-Angiotensina/imunologia , SARS-CoV-2
13.
FASEB J ; 35(7): e21746, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34151465

RESUMO

Bullous pemphigoid (BP), an autoimmune skin disease, is characterized by autoantibodies against hemidesmosomal proteins in the skin and mucous membranes. Neutrophils infiltrate BP skin lesions, however, their role in immune dysregulation remains unclear. We investigated whether BP involves aberrant neutrophil extracellular traps (NETs) formation in skin lesions and circulation; and examined the triggers and deleterious immuno-inflammatory consequences. In the present study, we found that circulating NET-related biomarker levels increased in serum and blister fluid of BP patients and significantly correlated with disease severity. Additionally, circulating neutrophils from BP patients displayed enhanced spontaneous NETs formation than healthy controls. In vitro, BP180-NC16A immune complexes-induced NETosis in neutrophils from BP patients, which was abrogated by Fcγ receptor and/or NADPH pathway blockade. Furthermore, the elevated levels of NETs from BP patients boosted autoantibody production by inducing B-cell differentiation into plasma cells, mediated by MAPK P38 cascade activation. Together, our findings provide strong evidence that NETs are involved in a pathogenic loop, causing excessive differentiation of B cells and promotion of autoantibody production. Hence, targeting aberrant neutrophil responses will provide novel potential targets for the treatment of BP.


Assuntos
Formação de Anticorpos/imunologia , Linfócitos B/imunologia , Diferenciação Celular/imunologia , Armadilhas Extracelulares/imunologia , Neutrófilos/imunologia , Penfigoide Bolhoso/imunologia , Autoanticorpos/imunologia , Autoantígenos/imunologia , Doenças Autoimunes/imunologia , Doenças Autoimunes/metabolismo , Linfócitos B/metabolismo , Biomarcadores/metabolismo , Vesícula/imunologia , Vesícula/metabolismo , Armadilhas Extracelulares/metabolismo , Humanos , Inflamação/imunologia , Inflamação/metabolismo , Neutrófilos/metabolismo , Penfigoide Bolhoso/metabolismo , Plasmócitos/imunologia , Plasmócitos/metabolismo , Receptores de IgG/imunologia , Transdução de Sinais/imunologia , Pele/imunologia , Pele/metabolismo , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo
14.
Front Immunol ; 12: 627986, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34093522

RESUMO

Seropositive rheumatoid arthritis (RA) is characterized by the presence of rheumatoid factor (RF) and anti-citrullinated protein autoantibodies (ACPA) with different fine-specificities. Yet, other serum anti-modified protein autoantibodies (AMPA), e.g. anti-carbamylated (Carb), -acetylated (KAc), and malondialdehyde acetaldehyde (MAA) modified protein antibodies, have been described. In this comprehensive study, we analyze 30 different IgG and IgA AMPA reactivities to Cit, Carb, KAc, and MAA antigens detected by ELISA and autoantigen arrays in N=1985 newly diagnosed RA patients. Association with patient characteristics such as smoking and disease activity were explored. Carb and KAc reactivities by different assays were primarily seen in patients also positive for anti-citrulline reactivity. Modified vimentin (mod-Vim) peptides were used for direct comparison of different AMPA reactivities, revealing that IgA AMPA recognizing mod-Vim was mainly detected in subsets of patients with high IgG anti-Cit-Vim levels and a history of smoking. IgG reactivity to acetylation was mainly detected in a subset of patients with Cit and Carb reactivity. Anti-acetylated histone reactivity was RA-specific and associated with high anti-CCP2 IgG levels, multiple ACPA fine-specificities, and smoking status. This reactivity was also found to be present in CCP2+ RA-risk individuals without arthritis. Our data further demonstrate that IgG autoreactivity to MAA was increased in RA compared to controls with highest levels in CCP2+ RA, but was not RA-specific, and showed low correlation with other AMPA. Anti-MAA was instead associated with disease activity and was not significantly increased in CCP2+ individuals at risk of RA. Notably, RA patients could be subdivided into four different subsets based on their AMPA IgG and IgA reactivity profiles. Our serology results were complemented by screening of monoclonal antibodies derived from single B cells from RA patients for the same antigens as the RA cohort. Certain CCP2+ clones had Carb or Carb+KAc+ multireactivity, while such reactivities were not found in CCP2- clones. We conclude that autoantibodies exhibiting different patterns of ACPA fine-specificities as well as Carb and KAc reactivity are present in RA and may be derived from multireactive B-cell clones. Carb and KAc could be considered reactivities within the "Cit-umbrella" similar to ACPA fine-specificities, while MAA reactivity is distinctly different.


Assuntos
Artrite Reumatoide/imunologia , Autoanticorpos/sangue , Autoantígenos/imunologia , Autoimunidade , Imunoglobulina A/sangue , Imunoglobulina G/sangue , Processamento de Proteína Pós-Traducional , Acetilação , Adulto , Idoso , Anticorpos Anti-Proteína Citrulinada/sangue , Especificidade de Anticorpos , Artrite Reumatoide/sangue , Artrite Reumatoide/diagnóstico , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Malondialdeído/imunologia , Pessoa de Meia-Idade , Peptídeos Cíclicos/imunologia , Carbamilação de Proteínas
15.
J Neuroimmunol ; 357: 577598, 2021 08 15.
Artigo em Inglês | MEDLINE | ID: mdl-34099270

RESUMO

Epidemiologic data on neuronal surface antibody (NSAb)-associated autoimmune encephalitides (NSAE) are scarce and heterogeneous. We review our 13-year-long biobank-data collection and provide the incidence of NSAE in two Italian provinces (approx. Population of 1,400,000) over a 5-year period (July 2013-June 2018). NSAbs were diagnosed in 75 out of 1179 tested patients (6.4%). The most common NSAbs were anti-LGI1 (30 cases), followed by NMDAR (24). Eleven cases of NSAE were diagnosed in Treviso and Trento provinces with an estimated incidence of 1.54 per 1,000,000 population (LGI1-encephalitis 0.84; C.I. 0.38-1.88). LGI1-E is the most frequent NSAE among adults.


Assuntos
Autoanticorpos/imunologia , Autoantígenos/imunologia , Encefalite Límbica/epidemiologia , Encefalite Límbica/imunologia , Neurônios/imunologia , Idoso , Feminino , Humanos , Incidência , Itália/epidemiologia , Masculino , Pessoa de Meia-Idade , Adulto Jovem
16.
Hypertens Res ; 44(9): 1047-1053, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34099884

RESUMO

There is currently a respiratory disease outbreak caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). After rapid development, RNA vaccines and adenoviral vector vaccines were approved within a year, which has demonstrated the strong impact of preventing infectious diseases using gene therapy technology. Furthermore, intensive immunological analysis has been performed to evaluate the efficiency and safety of these vaccines, potentially allowing for rapid progress in vaccine technology. After the coronavirus disease 2019 (COVID-19) era, the novel vaccine technology developed will expand to other vaccines. We have been developing vaccines for chronic diseases, such as hypertension, for >10 years. Regarding the development of vaccines against self-antigens (i.e., angiotensin II), the vaccine should efficiently induce a blocking antibody response against the self-antigen without activating cytotoxic T cells. Therefore, the epitope vaccine approach has been proposed to induce antibody production in response to a combination of a B cell epitope and exogenous T cell epitopes through major histocompatibility complex molecules. When these vaccines are established as therapeutic options for hypertension, their administration regimen, which might be a few times per year, will replace daily medication use. Thus, therapeutic vaccines for hypertension may be a novel option to control the progression of cerebrovascular diseases. Hopefully, the accumulation of immunological findings and vaccine technology advances due to COVID-19 will provide a novel concept for vaccines for chronic diseases.


Assuntos
Autoantígenos/imunologia , Vacinas contra COVID-19/imunologia , COVID-19/prevenção & controle , Hipertensão/terapia , SARS-CoV-2/imunologia , Vacinas/uso terapêutico , Doença Crônica , Humanos
18.
Int J Mol Sci ; 22(11)2021 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-34071130

RESUMO

The diagnosis of autoimmune polyglandular syndrome (APS) types 1/2 is difficult due to their rarity and nonspecific clinical manifestations. APS-1 development can be identified with assays for autoantibodies against cytokines, and APS-2 development with organ-specific antibodies. In this study, a microarray-based multiplex assay was proposed for simultaneous detection of both organ-specific (anti-21-OH, anti-GAD-65, anti-IA2, anti-ICA, anti-TG, and anti-TPO) and APS-1-specific (anti-IFN-ω, anti-IFN-α-2a, and anti-IL-22) autoantibodies. Herein, 206 serum samples from adult patients with APS-1, APS-2, isolated autoimmune endocrine pathologies or non-autoimmune endocrine pathologies and from healthy donors were analyzed. The prevalence of autoantibodies differed among the groups of healthy donors and patients with non-, mono- and multi-endocrine diseases. APS-1 patients were characterized by the presence of at least two specific autoantibodies (specificity 99.5%, sensitivity 100%). Furthermore, in 16 of the 18 patients, the APS-1 assay revealed triple positivity for autoantibodies against IFN-ω, IFN-α-2a and IL-22 (specificity 100%, sensitivity 88.9%). No anti-cytokine autoantibodies were found in the group of patients with non-APS-1 polyendocrine autoimmunity. The accuracy of the microarray-based assay compared to ELISA for organ-specific autoantibodies was 88.8-97.6%. This multiplex assay can be part of the strategy for diagnosing and predicting the development of APS.


Assuntos
Autoanticorpos/sangue , Poliendocrinopatias Autoimunes/imunologia , Adolescente , Adulto , Autoantígenos/imunologia , Doenças do Sistema Endócrino/sangue , Doenças do Sistema Endócrino/imunologia , Feminino , Humanos , Proteínas Imobilizadas/imunologia , Interferon Tipo I/imunologia , Interferon alfa-2/imunologia , Interleucinas/imunologia , Masculino , Análise em Microsséries/métodos , Pessoa de Meia-Idade , Especificidade de Órgãos , Poliendocrinopatias Autoimunes/sangue , Poliendocrinopatias Autoimunes/diagnóstico , Sensibilidade e Especificidade , Adulto Jovem
19.
Front Immunol ; 12: 625311, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33986742

RESUMO

Identification of the antigens associated with antibodies is vital to understanding immune responses in the context of infection, autoimmunity, and cancer. Discovering antigens at a proteome scale could enable broader identification of antigens that are responsible for generating an immune response or driving a disease state. Although targeted tests for known antigens can be straightforward, discovering antigens at a proteome scale using protein and peptide arrays is time consuming and expensive. We leverage Serum Epitope Repertoire Analysis (SERA), an assay based on a random bacterial display peptide library coupled with next generation sequencing (NGS), to power the development of Protein-based Immunome Wide Association Study (PIWAS). PIWAS uses proteome-based signals to discover candidate antibody-antigen epitopes that are significantly elevated in a subset of cases compared to controls. After demonstrating statistical power relative to the magnitude and prevalence of effect in synthetic data, we apply PIWAS to systemic lupus erythematosus (SLE, n=31) and observe known autoantigens, Smith and Ribosomal protein P, within the 22 highest scoring candidate protein antigens across the entire human proteome. We validate the magnitude and location of the SLE specific signal against the Smith family of proteins using a cohort of patients who are positive by predicate anti-Sm tests. To test the generalizability of the method in an additional autoimmune disease, we identified and validated autoantigenic signals to SSB, CENPA, and keratin proteins in a cohort of individuals with Sjogren's syndrome (n=91). Collectively, these results suggest that PIWAS provides a powerful new tool to discover disease-associated serological antigens within any known proteome.


Assuntos
Autoantígenos/imunologia , Autoimunidade , Epitopos Imunodominantes , Lúpus Eritematoso Sistêmico/imunologia , Proteoma , Proteômica , Síndrome de Sjogren/imunologia , Autoanticorpos/sangue , Autoantígenos/genética , Autoantígenos/metabolismo , Estudos de Casos e Controles , Simulação por Computador , Bases de Dados de Proteínas , Ensaio de Imunoadsorção Enzimática , Humanos , Lúpus Eritematoso Sistêmico/sangue , Lúpus Eritematoso Sistêmico/genética , Biblioteca de Peptídeos , Reprodutibilidade dos Testes , Testes Sorológicos , Síndrome de Sjogren/sangue , Síndrome de Sjogren/genética
20.
Front Immunol ; 12: 606963, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34054794

RESUMO

Toxoplasma gondii infection can trigger autoreactivity by different mechanisms. In the case of ocular toxoplasmosis, disruption of the blood-retinal barrier may cause exposure of confined retinal antigens such as recoverin. Besides, cross-reactivity can be induced by molecular mimicry of parasite antigens like HSP70, which shares 76% identity with the human ortholog. Autoreactivity can be a determining factor of clinical manifestations in the eye and in the central nervous system. We performed a prospective observational study to determine the presence of autoantibodies against recoverin and HSP70 by indirect ELISA in the serum of 65 patients with ocular, neuro-ophthalmic and congenital cerebral toxoplasmosis. We found systemic autoantibodies against recoverin and HSP70 in 33.8% and 15.6% of individuals, respectively. The presence of autoantibodies in cases of OT may be related to the severity of clinical manifestations, while in cases with CNS involvement they may have a protective role. Unexpectedly, anti-recoverin antibodies were found in patients with cerebral involvement, without ocular toxoplasmosis; therefore, we analyzed and proved cross-reactivity between recoverin and a brain antigen, hippocalcin, so the immunological phenomenon occurring in one immune-privileged organ (e.g. the central nervous system) could affect the environment of another (egg. the eye).


Assuntos
Autoanticorpos/imunologia , Autoantígenos/imunologia , Interações Hospedeiro-Parasita/imunologia , Toxoplasmose Cerebral/imunologia , Toxoplasmose Congênita/imunologia , Toxoplasmose Ocular/imunologia , Adolescente , Adulto , Sequência de Aminoácidos , Antígenos de Protozoários/imunologia , Criança , Pré-Escolar , Reações Cruzadas/imunologia , Feminino , Proteínas de Choque Térmico HSP70/química , Proteínas de Choque Térmico HSP70/imunologia , Hipocalcina/química , Hipocalcina/imunologia , Humanos , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Recoverina/química , Recoverina/imunologia , Toxoplasma/imunologia , Toxoplasmose Cerebral/diagnóstico , Toxoplasmose Cerebral/parasitologia , Toxoplasmose Congênita/diagnóstico , Toxoplasmose Congênita/parasitologia , Toxoplasmose Ocular/diagnóstico , Toxoplasmose Ocular/parasitologia , Adulto Jovem
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...