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1.
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
2.
Pan Afr Med J ; 40: 27, 2021.
Artigo em Francês | MEDLINE | ID: mdl-34733395

RESUMO

Stiff person syndrome (SPS) is a rare disease affecting the central nervous system which can be autoimmune, paraneoplastic or idiopathic in origin. Its typical classic presentation is characterized by progressive stiffness of the trunk and limbs, associated with spasms. The diagnosis is supported by the existence of continuous and spontaneous muscle activity on electroneuromyogram detection, the presence of serum anti-GAD antibodies, and a response to benzodiazepines. We report the case of a 46-year-old patient with a classic form of autoimmune stiff person syndrome associated with dermatitis herpetiformis.


Assuntos
Dermatite Herpetiforme/diagnóstico , Rigidez Muscular Espasmódica/diagnóstico , Autoanticorpos/imunologia , Dermatite Herpetiforme/imunologia , Humanos , Masculino , Pessoa de Meia-Idade , Rigidez Muscular Espasmódica/imunologia
3.
Front Immunol ; 12: 773352, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34745149

RESUMO

Anti-MDA5 dermatomyositis is a rare systemic autoimmune disease, historically described in Japanese patients with clinically amyopathic dermatomyositis and life-threatening rapidly progressive interstitial lung disease. Subsequently, the complete clinical spectrum of the disease was enriched by skin, articular and vascular manifestations. Depending on the predominance of these symptoms, three distinct clinical phenotypes with different prognosis are now defined. To date, the only known molecular component shared by the three entities are specific antibodies targeting MDA5, a cytosolic protein essential for antiviral host immune responses. Several biological tools have emerged to detect these antibodies, with drawbacks and limitations for each of them. However, the identification of this highly specific serological marker of the disease raises the question of its role in the pathogenesis. Although current knowledge on the pathogenic mechanisms that take place in the disease are still in their enfancy, several lines of evidence support a central role of interferon-mediated vasculopathy in the development of skin and lung lesions, as well as a possible pathogenic involvement of anti-MDA5 antibodies. Here, we review the clinical and biological evidences in favor of these hypothesis, and we discuss the contribution of emerging therapies that shed some light on the pathogenesis of the disease.


Assuntos
Autoanticorpos/imunologia , Vasos Sanguíneos/patologia , Dermatomiosite/imunologia , Helicase IFIH1 Induzida por Interferon/imunologia , Doenças Pulmonares Intersticiais/imunologia , Pele/patologia , Animais , Dermatomiosite/terapia , Humanos , Interferons/metabolismo , Doenças Pulmonares Intersticiais/terapia , Fenótipo
4.
Cells ; 10(10)2021 10 18.
Artigo em Inglês | MEDLINE | ID: mdl-34685765

RESUMO

Several recent reports have highlighted the onset of vaccine-induced thrombotic thrombocytopaenia (VITT) in some recipients (approximately 1 case out of 100k exposures) of the ChAdOx1 nCoV-19 vaccine (AstraZeneca). Although the underlying events leading to this blood-clotting phenomenon has yet to be elucidated, several critical observations present a compelling potential mechanism. Thrombus formation requires the von Willebrand (VWF) protein to be in ultra-large multimeric state. The conservation of this state is controlled by the ADAMTS13 enzyme, whose proteolytic activity reduces the size of VWF multimers, keeping blood clotting at bay. However, ADAMTS13 cannot act on VWF that is bound to platelet factor 4 (PF4). As such, it is of particular interest to note that a common feature between subjects presenting with VITT is high titres of antibodies against PF4. This raises the possibility that these antibodies preserve the stability of ultra-large VWF complexes, leading to the formation of endothelium-anchored VWF strings, which are capable of recruiting circulating platelets and causing uncontrolled thrombosis in terminal capillaries. Here, we share our viewpoint about the current understanding of the VITT pathogenesis involving the prevention of ADAMTS13's activity on VWF by PF4 antibody-mediated stabilisation/ protection of the PF4-VWF complex.


Assuntos
Proteína ADAMTS13/metabolismo , Vacinas contra COVID-19/efeitos adversos , COVID-19/prevenção & controle , Trombocitopenia/imunologia , Anticorpos , Autoanticorpos/imunologia , Plaquetas/metabolismo , Cristalografia por Raios X , Células Endoteliais/imunologia , Humanos , Fator Plaquetário 4/metabolismo , Polimorfismo Genético , Domínios Proteicos , Trombocitopenia/etiologia , Trombose/etiologia , Fator de von Willebrand/metabolismo
5.
Int J Mol Sci ; 22(19)2021 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-34638855

RESUMO

Rheumatoid Arthritis (RA) is a chronic autoimmune disease characterized by joint inflammation, affecting approximately 1% of the general population. To alleviate symptoms and ameliorate joint damage, chronic use of immunosuppressives is needed. However, these treatments are only partially effective and may lead to unwanted side effects. Therefore, a more profound understanding of the pathophysiology might lead to more effective therapies, or better still, a cure. The presence of autoantibodies in RA indicates that B cells might have a pivotal role in the disease. This concept is further supported by the fact that a diverse antibody response to various arthritis-related epitopes is associated with arthritis development. In this context, attention has focused in recent years on the role of Germinal Centers (GCs) in RA. Since GCs act as the main anatomic location of somatic hypermutations, and, thus, contributing to the diversity and specificity of (auto) antibodies, it has been speculated that defects in germinal center reactions might be crucial in the initiation and maintenance of auto-immune events. In this paper, we discuss current evidence that various processes within GCs can result in the aberrant production of B cells that possess autoreactive properties and might result in the production of RA related autoantibodies. Secondly, we discuss various (pre-)clinical studies that have targeted various GC processes as novel therapies for RA treatment.


Assuntos
Artrite Reumatoide/imunologia , Autoanticorpos/imunologia , Linfócitos B/imunologia , Epitopos/imunologia , Centro Germinativo/imunologia , Imunidade Adaptativa/imunologia , Animais , Antígenos/imunologia , Apoptose/imunologia , Linfócitos B/metabolismo , Centro Germinativo/citologia , Humanos
6.
Int J Mol Sci ; 22(19)2021 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-34638916

RESUMO

Rheumatoid arthritis (RA) is caused by prolonged periodic interactions between genetic, environmental, and immunologic factors. Posttranslational modifications (PTMs) such as citrullination, carbamylation, and acetylation are correlated with the pathogenesis of RA. PTM and cell death mechanisms such as apoptosis, autophagy, NETosis, leukotoxic hypercitrullination (LTH), and necrosis are related to each other and induce autoantigenicity. Certain microbial infections, such as those caused by Porphyromonasgingivalis, Aggregatibacter actinomycetemcomitans, and Prevotella copri, can induce autoantigens in RA. Anti-modified protein antibodies (AMPA) containing anti-citrullinated protein/peptide antibodies (ACPAs), anti-carbamylated protein (anti-CarP) antibodies, and anti-acetylated protein antibodies (AAPAs) play a role in pathogenesis as well as in prediction, diagnosis, and prognosis. Interestingly, smoking is correlated with both PTMs and AMPAs in the development of RA. However, there is lack of evidence that smoking induces the generation of AMPAs.


Assuntos
Artrite Reumatoide/imunologia , Citrulinação/imunologia , Carbamilação de Proteínas/imunologia , Processamento de Proteína Pós-Traducional/imunologia , Acetilação , Artrite Reumatoide/diagnóstico , Artrite Reumatoide/metabolismo , Autoanticorpos/imunologia , Autoantígenos/imunologia , Infecções Bacterianas/imunologia , Infecções Bacterianas/microbiologia , Reações Cruzadas/imunologia , Humanos
7.
Pan Afr Med J ; 39: 243, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34659616

RESUMO

Anti-glomerular basement membrane (anti-GBM) disease was usually described as a small vessel vasculitis presenting with acute kidney injury, haematuria and non-nephrotic proteinuria. We report a case of anti-GBM disease revealed by an intense nephrotic syndrome. The urinary protein level was 12g/day. Renal biopsy only showed crescent glomerulonephritis with linear staining of IgG in direct immunofluorescence without other glomerulonephritis. Immunoglobulin G (IgG) anti-GBM antibody titer was elevated.


Assuntos
Doença Antimembrana Basal Glomerular/diagnóstico , Síndrome Nefrótica/diagnóstico , Adulto , Doença Antimembrana Basal Glomerular/complicações , Autoanticorpos/imunologia , Biópsia , Humanos , Imunoglobulina G/imunologia , Masculino , Síndrome Nefrótica/etiologia , Proteinúria/etiologia
8.
Front Immunol ; 12: 672846, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34616389

RESUMO

Purpose: Brain 18F-fluorodeoxyglucose positron emission tomography (FDG PET) is a sensitive technique for assisting in the diagnosis of patients with anti-leucine-rich glioma-inactivated 1 (LGI1) antibody encephalitis. However, the common pattern of this disorder assessed by FDG PET remains unknown. The present study aimed to explore the glucose metabolic patterns of this disorder based on PET voxel analysis. Methods: This retrospective study enrolled 25 patients with anti-LGI1 encephalitis, who were admitted in Beijing Tiantan Hospital between September 2014 and July 2019. The glucose metabolic pattern was compared between the included patients and 44 age- and gender-matched healthy controls using Statistical Parametric Mapping. Then, the correlation between the metabolic pattern and scaled activities of daily living (ADLs) of the patients was assessed. Results: The median time from symptom onset to PET scans was 9 w (range:2-53w). The groupwise analysis revealed that patients with anti-LGI1 encephalitis had left hippocampal hypermetabolism and hypometabolism in almost all neocortical regions. The individual-level results showed most patients presented a decreased metabolism in neocortical regions, as well as an increase in metabolism in the hippocampus and basal ganglia. Furthermore, the metabolic gradient between hippocampus and neocortical regions was positively associated with the ADLs (frontal lobe, r=0.529, P=0.008; parietal lobe, r=0.474, P=0.019; occipital lobe, r=0.413, P=0.045; temporal lobe, r=0.490, P=0.015), respectively. In addition, the patients with facio-brachial dystonic seizures (FBDS) presented bilateral putamen hypermetabolism, when compared to patients without FBDS and healthy controls. Conclusion: Subcortical hypermetabolism associated with cortical hypometabolism presented with a common metabolic pattern in patients with anti-LGI1 encephalitis in the present study. The resolution of the metabolic gradient of the hippocampal hypermetabolism and neocortical hypometabolism may bring about improved clinical neurologic disability.


Assuntos
Encéfalo/diagnóstico por imagem , Encefalite/diagnóstico por imagem , Doença de Hashimoto/diagnóstico por imagem , Tomografia por Emissão de Pósitrons , Atividades Cotidianas , Adolescente , Adulto , Idoso , Autoanticorpos/imunologia , Encéfalo/imunologia , Encéfalo/metabolismo , Encefalite/imunologia , Encefalite/metabolismo , Feminino , Fluordesoxiglucose F18 , Doença de Hashimoto/imunologia , Doença de Hashimoto/metabolismo , Humanos , Peptídeos e Proteínas de Sinalização Intracelular/imunologia , Masculino , Pessoa de Meia-Idade , Compostos Radiofarmacêuticos , Estudos Retrospectivos , Adulto Jovem
9.
J Neuroinflammation ; 18(1): 245, 2021 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-34711233

RESUMO

Approximately 30% of individuals with severe SARS-CoV-2 infections also develop neurological and psychiatric complaints. In rare cases, the occurrence of autoimmune encephalitis has been reported after SARS-CoV-2 infection. In this systematic review, we have identified eight SARS-CoV-2-associated cases of anti-NMDA receptor encephalitis. All had cerebrospinal fluid antibodies against the NMDA receptor and a recent onset of working memory deficits, altered mental status, or psychiatric symptoms, such as confusion, agitation, auditory hallucination, catatonia and speech dysfunction. All patients received high-dose steroid and immunoglobulin therapeutics and conditions improved in each case. These findings suggest that clinical attention should be paid to warning signs of autoimmune encephalitis in severe COVID-19 cases. If characteristic features of autoimmune encephalitis are present, autoantibody diagnostics should be performed and confirmed cases should be treated with immunotherapy to minimize neurological impairments.


Assuntos
Encefalite Antirreceptor de N-Metil-D-Aspartato/virologia , COVID-19/complicações , Transtornos Mentais/virologia , Receptores de N-Metil-D-Aspartato/imunologia , Adolescente , Adulto , Autoanticorpos/imunologia , COVID-19/imunologia , Criança , Feminino , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Mimetismo Molecular , SARS-CoV-2/imunologia , Adulto Jovem
10.
Clin Immunol ; 232: 108869, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34600127

RESUMO

Children with idiopathic nephrotic syndrome (INS) usually have podocyte injury, and recent studies suggest a B cell dysfunction in INS. Therefore, this study attempts to screen and identify the podocyte autoantibodies in patients. Two-dimensional electrophoresis and mass spectrometry were used to screen and identify the pathogenic podocyte autoantibodies in children with INS. The positive rate, expression pattern, and clinical correlation of these podocyte autoantibodies in children with INS were determined by clinical study. At least 66% of INS children have podocyte autoantibodies. Seven podocyte autoantibodies closely related to INS were screened and identified for the first time in this study. These podocyte autoantibodies are positively correlated with proteinuria, and its titer will decrease rapidly after effective treatment. In this study, a group of new disease subgroup-"autoimmune podocytes" were identified by podocyte autoantibodies.


Assuntos
Autoanticorpos/imunologia , Autoantígenos/imunologia , Doenças Autoimunes/imunologia , Síndrome Nefrótica/imunologia , Podócitos/imunologia , Adolescente , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Proteinúria/imunologia
11.
Life Sci Alliance ; 4(11)2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34504035

RESUMO

High levels of autoimmune antibodies are observed in COVID-19 patients but their specific contribution to disease severity and clinical manifestations remains poorly understood. We performed a retrospective study of 115 COVID-19 hospitalized patients with different degrees of severity to analyze the generation of autoimmune antibodies to common antigens: a lysate of erythrocytes, the lipid phosphatidylserine (PS) and DNA. High levels of IgG autoantibodies against erythrocyte lysates were observed in a large percentage (up to 36%) of patients. Anti-DNA and anti-PS antibodies determined upon hospital admission correlated strongly with later development of severe disease, showing a positive predictive value of 85.7% and 92.8%, respectively. Patients with positive values for at least one of the two autoantibodies accounted for 24% of total severe cases. Statistical analysis identified strong correlations between anti-DNA antibodies and markers of cell injury, coagulation, neutrophil levels and erythrocyte size. Anti-DNA and anti-PS autoantibodies may play an important role in the pathogenesis of COVID-19 and could be developed as predictive biomarkers for disease severity and specific clinical manifestations.


Assuntos
Anticorpos Antinucleares/imunologia , Autoanticorpos/imunologia , COVID-19/imunologia , COVID-19/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Antinucleares/sangue , Autoanticorpos/sangue , Biomarcadores , DNA/química , DNA/imunologia , Eritrócitos/imunologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fosfatidilserinas/imunologia , Prognóstico , Estudos Retrospectivos , SARS-CoV-2/isolamento & purificação , Índice de Gravidade de Doença
12.
Front Immunol ; 12: 722979, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34489972

RESUMO

The immunopathology of type I diabetes (T1D) presents a complicated case in part because of the multifactorial origin of this disease. Typically, T1D is thought to occur as a result of autoimmunity toward islets of Langerhans, resulting in the destruction of insulin-producing cells (ß cells) and thus lifelong reliance on exogenous insulin. However, that explanation obscures much of the underlying mechanism, and the actual precipitating events along with the associated actors (latent viral infection, diverse immune cell types and their roles) are not completely understood. Notably, there is a malfunctioning in the regulation of cytotoxic CD8+ T cells that target endocrine cells through antigen-mediated attack. Further examination has revealed the likelihood of an imbalance in distinct subpopulations of tolerogenic and cytotoxic natural killer (NK) cells that may be the catalyst of adaptive immune system malfunction. The contributions of components outside the immune system, including environmental factors such as chronic viral infection also need more consideration, and much of the recent literature investigating the origins of this disease have focused on these factors. In this review, the details of the immunopathology of T1D regarding NK cell disfunction is discussed, along with how those mechanisms stand within the context of general autoimmune disorders. Finally, the rarer cases of latent autoimmune, COVID-19 (viral), and immune checkpoint inhibitor (ICI) induced diabetes are discussed as their exceptional pathology offers insight into the evolution of the disease as a whole.


Assuntos
Doenças Autoimunes/imunologia , Diabetes Mellitus Tipo 1/imunologia , Diabetes Mellitus Tipo 1/patologia , Células Matadoras Naturais/imunologia , Células Matadoras Naturais/patologia , Autoanticorpos/imunologia , Doenças Autoimunes/patologia , COVID-19/complicações , Diabetes Mellitus Tipo 1/etiologia , Humanos , Insulina/metabolismo , Células Secretoras de Insulina/imunologia , Viroses/complicações
13.
PLoS One ; 16(9): e0257016, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34478478

RESUMO

BACKGROUND: Activation of the immune system is implicated in the Post-Acute Sequelae after SARS-CoV-2 infection (PASC) but the mechanisms remain unknown. Angiotensin-converting enzyme 2 (ACE2) cleaves angiotensin II (Ang II) resulting in decreased activation of the AT1 receptor and decreased immune system activation. We hypothesized that autoantibodies against ACE2 may develop after SARS-CoV-2 infection, as anti-idiotypic antibodies to anti-spike protein antibodies. METHODS AND FINDINGS: We tested plasma or serum for ACE2 antibodies in 67 patients with known SARS-CoV-2 infection and 13 with no history of infection. None of the 13 patients without history of SARS-CoV-2 infection and 1 of the 20 outpatients that had a positive PCR test for SARS-CoV-2 had levels of ACE2 antibodies above the cutoff threshold. In contrast, 26/32 (81%) in the convalescent group and 14/15 (93%) of patients acutely hospitalized had detectable ACE2 antibodies. Plasma from patients with antibodies against ACE2 had less soluble ACE2 activity in plasma but similar amounts of ACE2 protein compared to patients without ACE2 antibodies. We measured the capacity of the samples to inhibit ACE2 enzyme activity. Addition of plasma from patients with ACE2 antibodies led to decreased activity of an exogenous preparation of ACE2 compared to patients that did not have antibodies. CONCLUSIONS: Many patients with a history of SARS-CoV-2 infection have antibodies specific for ACE2. Patients with ACE2 antibodies have lower activity of soluble ACE2 in plasma. Plasma from these patients also inhibits exogenous ACE2 activity. These findings are consistent with the hypothesis that ACE2 antibodies develop after SARS-CoV-2 infection and decrease ACE2 activity. This could lead to an increase in the abundance of Ang II, which causes a proinflammatory state that triggers symptoms of PASC.


Assuntos
Autoanticorpos/sangue , COVID-19/imunologia , SARS-CoV-2/isolamento & purificação , Glicoproteína da Espícula de Coronavírus/sangue , Angiotensina II/sangue , Angiotensina II/imunologia , Enzima de Conversão de Angiotensina 2/genética , Autoanticorpos/imunologia , Autoanticorpos/isolamento & purificação , COVID-19/sangue , COVID-19/virologia , Feminino , Humanos , Masculino , Peptidil Dipeptidase A/sangue , Receptor Tipo 1 de Angiotensina/sangue , Receptor Tipo 1 de Angiotensina/genética , Receptor Tipo 1 de Angiotensina/imunologia , Sistema Renina-Angiotensina/genética , Sistema Renina-Angiotensina/imunologia , SARS-CoV-2/genética , SARS-CoV-2/imunologia , Glicoproteína da Espícula de Coronavírus/imunologia , Glicoproteína da Espícula de Coronavírus/isolamento & purificação
14.
Nat Commun ; 12(1): 5417, 2021 09 14.
Artigo em Inglês | MEDLINE | ID: mdl-34521836

RESUMO

COVID-19 is associated with a wide range of clinical manifestations, including autoimmune features and autoantibody production. Here we develop three protein arrays to measure IgG autoantibodies associated with connective tissue diseases, anti-cytokine antibodies, and anti-viral antibody responses in serum from 147 hospitalized COVID-19 patients. Autoantibodies are identified in approximately 50% of patients but in less than 15% of healthy controls. When present, autoantibodies largely target autoantigens associated with rare disorders such as myositis, systemic sclerosis and overlap syndromes. A subset of autoantibodies targeting traditional autoantigens or cytokines develop de novo following SARS-CoV-2 infection. Autoantibodies track with longitudinal development of IgG antibodies recognizing SARS-CoV-2 structural proteins and a subset of non-structural proteins, but not proteins from influenza, seasonal coronaviruses or other pathogenic viruses. We conclude that SARS-CoV-2 causes development of new-onset IgG autoantibodies in a significant proportion of hospitalized COVID-19 patients and are positively correlated with immune responses to SARS-CoV-2 proteins.


Assuntos
Autoanticorpos/imunologia , COVID-19/imunologia , Imunoglobulina G/imunologia , SARS-CoV-2/imunologia , Idoso , Anticorpos Antinucleares/sangue , Anticorpos Antinucleares/imunologia , Anticorpos Antivirais/sangue , Anticorpos Antivirais/imunologia , Autoanticorpos/sangue , Autoantígenos/imunologia , Doenças do Tecido Conjuntivo/imunologia , Citocinas/imunologia , Feminino , Hospitalização , Humanos , Imunoglobulina G/sangue , Masculino , Pessoa de Meia-Idade , SARS-CoV-2/patogenicidade , Proteínas Virais/imunologia
15.
Med Sci Monit ; 27: e934766, 2021 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-34538868

RESUMO

During the past two years, clinical studies have attempted to identify risk factors to predict clinical outcomes following infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In July 2021, a study using a high-throughput technique detected autoantibodies to chemokines, cytokines, and complement components in patients with symptomatic coronavirus disease 2019 (COVID-19). In August 2021, a study identified pre-existing autoantibodies to type 1 interferons (IFNs) in 10% of patients with severe COVID-19 but not asymptomatic individuals. Autoantibodies may be the long-awaited markers of clinical risk for severe COVID-19 in patients with SARS-CoV-2 infection. This Editorial aims to present some recent findings of autoantibodies to components of the immune system, including type 1 IFNs, and the risk of severe COVID-19.


Assuntos
Autoanticorpos/imunologia , COVID-19/imunologia , Interferon Tipo I/imunologia , SARS-CoV-2/imunologia , COVID-19/virologia , Humanos , Interferon Tipo I/genética , SARS-CoV-2/genética
16.
Front Immunol ; 12: 681714, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34539625

RESUMO

Background: Chronic spontaneous urticaria (CSU) is a common autoimmune skin disease. Little is known about the role of epigenetics in the pathogenesis of CSU. This study aimed to investigate genome-wide DNA methylation profile in whole blood of patients with CSU. Patients and Methods: Genome-wide DNA methylation levels in whole blood samples of 95 Chinese Han ethnicity adult CSU patients and 95 ethnicity-, age- and sex-matched healthy controls were analyzed using Illumina 850K methylation chip. The differentially methylated genes (DMGs) were screened out and then functionally annotated by the gene ontology and the Kyoto encyclopedia of genes and genomes databases. Results: A total of 439 differentially methylated positions (DMPs) (p < 0.01 and |Δß| ≥ 0.06) were identified with 380 hypomethylated and 59 hypermethylated. The average global DNA methylation levels of the 439 DMPs in the CSU patients were significantly lower than those in the healthy controls (p < 0.001). The distribution of the 439 DMPs was wide on chromosome 1 to 22 and chromosome X. Chromosome 6 embodied the largest number of DMPs (n = 51) and their annotated genes were predominantly related to autoimmunity. The 304 annotated DMGs were mainly enriched in autoimmune disease- and immune-related pathways. A total of 41 DMPs annotated to 28 DMGs were identified when p < 0.01 and |Δß| ≥ 0.1. Of the 28 DMGs, HLA-DPB2, HLA-DRB1, PPP2R5C, and LTF were associated with autoimmunity. CSU cases with elevated total IgE, positive anti-thyroid peroxidase IgG autoantibodies, positive anti-thyroglobulin IgG autoantibodies, angioedema, UASday > 4, or recurrent CSU showed phenotype-specific DMPs as compared with cases with normal total IgE, negative anti-thyroid peroxidase IgG autoantibodies, negative anti-thyroglobulin IgG autoantibodies, no angioedema, UASday ≤ 4, or non-recurrent CSU respectively. Conclusion: This study shows a distinct genome-wide DNA methylation profile in Chinese Han ethnicity adult CSU patients and indicates a role of epigenetics in the pathogenesis of CSU. The predominant enrichment of the CSU-associated DMGs in immunological pathways provides supportive evidence for the immunopathogenesis of CSU. Future research on the CSU-associated DMPs and DMGs will help discover potential therapeutic targets for CSU.


Assuntos
Urticária Crônica/etiologia , Metilação de DNA , Epigênese Genética , Transcriptoma , Autoanticorpos/sangue , Autoanticorpos/imunologia , Autoimunidade , Estudos de Casos e Controles , Urticária Crônica/diagnóstico , Biologia Computacional/métodos , Ilhas de CpG , Suscetibilidade a Doenças/imunologia , Perfilação da Expressão Gênica , Ontologia Genética , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Humanos , Imunoglobulina E/sangue , Imunoglobulina E/imunologia
17.
Sci Rep ; 11(1): 17886, 2021 09 09.
Artigo em Inglês | MEDLINE | ID: mdl-34504137

RESUMO

Rheumatoid arthritis (RA) is one of the most common autoimmune diseases worldwide. Due to high heterogeneity in disease manifestation, accurate and fast diagnosis of RA is difficult. This study analyzed the potential relationship between the infrared (IR) spectra obtained by attenuated total reflectance Fourier transform infrared spectroscopy (ATR-FTIR) and the presence of autoantibodies and antibodies against urease in sera. Additionally, the wave number of the IR spectrum that enabled the best differentiation between patients and healthy blood donors was investigated. Using a mathematical model involving principal component analysis and discriminant analysis, it was shown that the presence of anti-citrullinated protein antibody, rheumatoid factor, anti-neutrophil cytoplasmic antibodies, and anti-nuclear antibodies correlated significantly with the wave numbers in the IR spectra of the tested sera. The most interesting findings derived from determination of the best predictors for distinguishing RA. Characteristic features included an increased reaction with urease mimicking peptides and a correspondence with particular nucleic acid bands. Taken together, the results demonstrated the potential application of ATR-FTIR in the study of RA and identified potential novel markers of the disease.


Assuntos
Artrite Reumatoide/imunologia , Proteínas Mutadas de Ataxia Telangiectasia/imunologia , Autoanticorpos/imunologia , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Peptídeos/imunologia , Peptídeos Cíclicos/imunologia , Fator Reumatoide/sangue , Espectroscopia de Infravermelho com Transformada de Fourier/métodos
19.
Expert Opin Drug Metab Toxicol ; 17(10): 1223-1235, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34535065

RESUMO

Migraine is a prevalent medical condition and the second most disabling neurological disorder. Regarding its pathophysiology, calcitonin gene-related peptide (CGRP) plays a key role, and, consequently, specific antimigraine pharmacotherapy has been designed to target this system. Hence, apart from the gepants, the recently developed monoclonal antibodies (mAbs) are a novel approach to treat this disorder. In this review we consider the current knowledge on the mechanisms of action, specificity, safety, and efficacy of the above mAbs as prophylactic antimigraine agents, and examine the possible adverse events that these agents may trigger. Antimigraine mAbs act as direct scavengers of CGRP (galcanezumab, fremanezumab, and eptinezumab) or against the CGRP receptor (erenumab). Due to their long half-lives, these molecules have revolutionized the prophylactic treatment of this neurovascular disorder. Moreover, because of their physicochemical properties, these agents are hepato-friendly and do not cross the blood-brain barrier (highlighting the relevance of peripheral mechanisms in migraine). Nevertheless, apart from potential cardiovascular side effects, the interaction with AMY1 receptors and immunogenicity induced by autoantibodies against mAbs could be a concern for the safety of long-term treatment with these molecules.


Assuntos
Anticorpos Monoclonais/farmacologia , Peptídeo Relacionado com Gene de Calcitonina/imunologia , Transtornos de Enxaqueca/tratamento farmacológico , Animais , Anticorpos Monoclonais/efeitos adversos , Autoanticorpos/imunologia , Barreira Hematoencefálica/metabolismo , Doenças Cardiovasculares/induzido quimicamente , Humanos , Transtornos de Enxaqueca/imunologia , Transtornos de Enxaqueca/fisiopatologia , Receptores de Peptídeo Relacionado com o Gene de Calcitonina/imunologia
20.
PLoS One ; 16(9): e0256972, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34473764

RESUMO

High titers of anti-NMDAR1 autoantibodies in brain cause anti-NMDAR1 encephalitis that displays psychiatric symptoms of schizophrenia and/or other psychiatric disorders in addition to neurological symptoms. Low titers of anti-NMDAR1 autoantibodies are reported in the blood of a subset of the general human population and psychiatric patients. Since ~0.1-0.2% of blood circulating antibodies cross the blood-brain barriers and antibodies can persist for months and years in human blood, it is important to investigate whether chronic presence of these blood circulating anti-NMDAR1 autoantibodies may impair human cognitive functions and contribute to the development of psychiatric symptoms. Here, we generated mice carrying low titers of anti-NMDAR1 autoantibodies in blood against a single antigenic epitope of mouse NMDAR1. Mice carrying the anti-NMDAR1 autoantibodies are healthy and display no differences in locomotion, sensorimotor gating, and contextual memory compared to controls. Chronic presence of the blood circulating anti-NMDAR1 autoantibodies, however, is sufficient to impair T-maze spontaneous alternation in the integrity of blood-brain barriers across all 3 independent mouse cohorts, indicating a robust cognitive deficit in spatial working memory and/or novelty detection. Our studies implicate that chronic presence of low titers of blood circulating anti-NMDAR1 autoantibodies may impair cognitive functions in both the general healthy human population and psychiatric patients.


Assuntos
Autoanticorpos/sangue , Autoanticorpos/imunologia , Cognição , Disfunção Cognitiva/sangue , Disfunção Cognitiva/imunologia , Proteínas do Tecido Nervoso/imunologia , Receptores de N-Metil-D-Aspartato/imunologia , Adjuvantes Imunológicos/administração & dosagem , Animais , Comportamento Animal , Barreira Hematoencefálica/imunologia , Adjuvante de Freund/administração & dosagem , Locomoção/imunologia , Masculino , Memória de Curto Prazo , Camundongos , Camundongos Endogâmicos C57BL , Modelos Animais , Mycobacterium tuberculosis/imunologia , Proteínas do Tecido Nervoso/química , Peptídeos/administração & dosagem , Peptídeos/imunologia , Receptores de N-Metil-D-Aspartato/química , Memória Espacial , Vacinação/métodos
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