Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 25.531
Filtrar
1.
Cells ; 11(20)2022 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-36291095

RESUMO

BACKGROUND: Tumor-associated antigens (TAAs) have been investigated for many years as potential early diagnosis tools, especially for hepatocellular carcinoma (HCC). Nonetheless, very few studies have focused on the Hispanic HCC group that may be associated with distinct etiological risk factors. In the present study, we investigated novel anti-TAA autoantibodies as diagnostic biomarkers for Hispanic HCC patients. METHODS: Novel TAA targets were identified by the serological proteome analysis (SERPA) and from differentially expressed HCC driver genes via bioinformatics. The autoantibody levels were validated by enzyme-linked immunosorbent assay (ELISA). RESULTS: Among 19 potential TAA targets, 4 anti-TAA autoantibodies were investigated as potential diagnostic biomarkers with significantly high levels in Hispanic HCC sera, including DNA methyltransferase 3A (DNMT3A), p16, Hear shock protein 60 (Hsp60), and Heat shock protein A5 (HSPA5). The area under the ROC curve (AUC) value of the single autoantibodies varies from 0.7505 to 0.8885. After combining all 4 autoantibodies, the sensitivity of the autoantibody panel increased to 75% compared to the single one with the highest value of 45.8%. In a separate analysis of the Asian cohort, autoantibodies against HSPA5 and p16 showed significantly elevated levels in HCC compared to normal healthy controls, but not for DNMT3A or HSP60. CONCLUSION: Anti-DNMT3A, p16, HSPA5, and HSP60 autoantibodies have the potential to be diagnostic biomarkers for Hispanic HCC patients, of which DNMT3A and HSP60 might be exclusive for Hispanic HCC diagnosis.


Assuntos
Anticorpos Antineoplásicos , Antígenos de Neoplasias , Autoanticorpos , Biomarcadores Tumorais , Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Antígenos de Neoplasias/imunologia , Autoanticorpos/sangue , Biomarcadores Tumorais/imunologia , Carcinoma Hepatocelular/sangue , Carcinoma Hepatocelular/diagnóstico , Chaperona BiP do Retículo Endoplasmático/imunologia , Hispânico ou Latino , Neoplasias Hepáticas/irrigação sanguínea , Neoplasias Hepáticas/diagnóstico , Proteoma , Anticorpos Antineoplásicos/sangue
2.
Clin Cancer Res ; 28(18): 4121-4130, 2022 09 15.
Artigo em Inglês | MEDLINE | ID: mdl-36106402

RESUMO

PURPOSE: Adjuvant immunotherapy produces durable benefit for patients with resected melanoma, but many develop recurrence and/or immune-related adverse events (irAE). We investigated whether baseline serum autoantibody (autoAb) signatures predicted recurrence and severe toxicity in patients treated with adjuvant nivolumab, ipilimumab, or ipilimumab plus nivolumab. EXPERIMENTAL DESIGN: This study included 950 patients: 565 from CheckMate 238 (408 ipilimumab versus 157 nivolumab) and 385 from CheckMate 915 (190 nivolumab versus 195 ipilimumab plus nivolumab). Serum autoAbs were profiled using the HuProt Human Proteome Microarray v4.0 (CDI Laboratories, Mayaguez, PR). Analysis of baseline differentially expressed autoAbs was followed by recurrence and severe toxicity signature building for each regimen, testing of the signatures, and additional independent validation for nivolumab using patients from CheckMate 915. RESULTS: In the nivolumab independent validation cohort, high recurrence score predicted significantly worse recurrence-free survival [RFS; adjusted HR (aHR), 3.60; 95% confidence interval (CI), 1.98-6.55], and outperformed a model composed of clinical variables including PD-L1 expression (P < 0.001). Severe toxicity score was a significant predictor of severe irAEs (aHR, 13.53; 95% CI, 2.59-86.65). In the ipilimumab test cohort, high recurrence score was associated with significantly worse RFS (aHR, 3.21; 95% CI, 1.38-7.45) and severe toxicity score significantly predicted severe irAEs (aHR, 11.04; 95% CI, 3.84-37.25). In the ipilimumab plus nivolumab test cohort, high autoAb recurrence score was associated with significantly worse RFS (aHR, 6.45; 95% CI, 1.48-28.02), and high severe toxicity score was significantly associated with severe irAEs (aHR, 23.44; 95% CI, 4.10-212.50). CONCLUSIONS: Baseline serum autoAb signatures predicted recurrence and severe toxicity in patients treated with adjuvant immunotherapy. Prospective testing of the signatures that include datasets with longer follow-up and rare but more severe toxicities will help determine their generalizability and potential clinical utility. See related commentary by Hassel and Luke, p. 3914.


Assuntos
Adjuvantes Imunológicos , Protocolos de Quimioterapia Combinada Antineoplásica , Autoanticorpos , Melanoma , Adjuvantes Imunológicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Autoanticorpos/sangue , Humanos , Inibidores de Checkpoint Imunológico , Ipilimumab , Nivolumabe , Estudos Prospectivos
4.
Yakugaku Zasshi ; 142(8): 837-853, 2022.
Artigo em Japonês | MEDLINE | ID: mdl-35908945

RESUMO

Myelin is a multilamellar membrane structure formed by oligodendrocytes in the central nervous system (CNS) and Schwann cells in the peripheral nervous system (PNS). It has been recognized as an insulator that is essential for the rapid and efficient propagation of action potentials by saltatory conduction. However, recently many studies have shown that myelin and myelin-forming cells interact with axons and regulate the nervous system far more actively than previously thought. For example, myelination changes axons dynamically and divides them into four distinct functional domains: node of Ranvier, paranode, juxtaparanode, and internode. Voltage-gated Na+ channels are clustered at the node, while K+ channels are at the juxtaparanode, and segregation of these channels by paranodal axoglial junction is necessary for proper axonal function. My research experience began at the neurology ward of the Niigata University Medical Hospital, where I saw a patient with peripheral neuropathy of unknown etiology more than 37 years ago. In the patient's serum, we found an autoantibody against a glycolipid enriched in the PNS. Since then, I have been interested in myelin because of its beautiful structure and unique roles in the nervous system. In this review, our recent studies related to CNS and PNS myelin are presented.


Assuntos
Bainha de Mielina , Nós Neurofibrosos , Autoanticorpos/sangue , Axônios/química , Sistema Nervoso Central/metabolismo , Humanos , Bainha de Mielina/química , Bainha de Mielina/imunologia , Bainha de Mielina/metabolismo , Bainha de Mielina/fisiologia , Células de Schwann/metabolismo
5.
J Child Neurol ; 37(8-9): 727-737, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35673711

RESUMO

BACKGROUND: The identification of immunoglobulin G antibodies against the aquaporin-4 channel (AQP-IgG) in the majority of adult patients differentiates neuromyelitis optica as a distinct disease entity. The high specificity of AQP4-IgG for neuromyelitis optica has allowed the identification of seropositive patients with atypical presentations of this disease. Neuromyelitis optica spectrum disorder has been increasingly recognized in children who demonstrate patterns of clinical involvement beyond the traditional boundaries of the optic pathways and spinal cord. METHODS: This is a single-center, retrospective review comparing demographic, clinical/paraclinical, and laboratory features of children and adults with a serologically confirmed diagnosis of AQP4-IgG-positive neuromyelitis optica spectrum disorder. RESULTS: Of 151 reviewed patient charts, 12 pediatric-onset and 31 adult-onset patients had AQP4-IgG-positive neuromyelitis optica spectrum disorder. The mean age of pediatric-onset neuromyelitis optica spectrum disorder was 12 ± 3.58 years with a female predilection (3:1). Pediatric patients showed more frequent involvement of the brainstem (6/12 [50%]); P = .008) and diencephalon (3/12 [25%]; P = .018). A preceding infection was identifiable in only 3 of 12 (25%) pediatric-onset patients. Moreover, disability as calculated on the expanded disability status scale was less severe in pediatric-onset cases compared to adult-onset cases in their most recent assessment (0 [0-9]) vs 6.5 [0-10]; P = .005). Pediatric-onset patients were also more likely to respond to treatment of acute episodes with corticosteroids ± intravenous immunoglobulin and/or plasmapheresis (Clinical Global Impression-Change scale: 2.5 [1-4] vs 4 [1-6], P = .009). INTERPRETATION: This retrospective study was able to compare and contrast pediatric- and adult-onset neuromyelitis optica spectrum disorder. Relative to their adult counterparts, pediatric-onset neuromyelitis optica spectrum disorder patients were more likely to respond to treatment and less likely to be disabled from their disease at follow-up. Therefore, pediatric-onset disease may represent a less virulent form of neuromyelitis optica spectrum disorder.


Assuntos
Aquaporina 4 , Autoanticorpos , Imunoglobulina G , Neuromielite Óptica , Adolescente , Adulto , Idade de Início , Aquaporina 4/imunologia , Autoanticorpos/sangue , Criança , Feminino , Humanos , Imunoglobulina G/sangue , Masculino , Neuromielite Óptica/diagnóstico por imagem , Neuromielite Óptica/imunologia , Estudos Retrospectivos , Testes Sorológicos
6.
Arch Toxicol ; 96(10): 2785-2797, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-35763063

RESUMO

Occupational exposure to trichloroethylene (TCE) causes a systemic skin disorder with hepatitis known as TCE hypersensitivity syndrome (TCE-HS). Human Leukocyte Antigen (HLA)-B*13:01 is its susceptibility factor; however, the immunological pathogenesis of TCE-HS remains unknown. We herein examined the hypothesis that autoantibodies to CYP2E1 are primarily involved in TCE-HS. A case-control study of 80 TCE-HS patients, 186 TCE-tolerant controls (TCE-TC), and 71 TCE-nonexposed controls (TCE-nonEC) was conducted to measure their serum anti-CYP2E1 antibody (IgG) levels. The effects of TCE exposure indices, such as 8-h time-weighted-average (TWA) airborne concentrations, urinary metabolite concentrations, and TCE usage duration; sex; smoking and drinking habits; and alanine aminotransferase (ALT) levels on the antibody levels were also analyzed in the two control groups. There were significant differences in anti-CYP2E1 antibody levels among the three groups: TCE-TC > TCE-HS patients > TCE-nonEC. Antibody levels were not different between HLA-B*13:01 carriers and noncarriers in TCE-HS patients and TCE-TC. The serum CYP2E1 measurement suggested increased immunocomplex levels only in patients with TCE-HS. Multiple regression analysis for the two control groups showed that the antibody levels were significantly higher by the TCE exposure. Women had higher antibody levels than men; however, smoking, drinking, and ALT levels did not affect the anti-CYP2E1 antibody levels. Anti-CYP2E1 antibodies were elevated at concentrations lower than the TWA concentration of 2.5 ppm for TCE exposure. Since HLA-B*13:01 polymorphism was not involved in the autoantibody levels, the possible mechanism underlying the pathogenesis of TCE-HS is that TCE exposure induces anti-CYP2E1 autoantibody production, and HLA-B*13:01 is involved in the development of TCE-HS.


Assuntos
Citocromo P-450 CYP2E1 , Síndrome de Hipersensibilidade a Medicamentos , Exposição Ocupacional , Tricloroetileno , Autoanticorpos/sangue , Autoanticorpos/genética , Autoanticorpos/imunologia , Estudos de Casos e Controles , Doença Hepática Induzida por Substâncias e Drogas/sangue , Doença Hepática Induzida por Substâncias e Drogas/genética , Doença Hepática Induzida por Substâncias e Drogas/imunologia , Citocromo P-450 CYP2E1/sangue , Citocromo P-450 CYP2E1/genética , Citocromo P-450 CYP2E1/imunologia , Síndrome de Hipersensibilidade a Medicamentos/sangue , Síndrome de Hipersensibilidade a Medicamentos/etiologia , Síndrome de Hipersensibilidade a Medicamentos/imunologia , Feminino , Antígenos HLA-B/sangue , Antígenos HLA-B/genética , Antígenos HLA-B/imunologia , Hepatite Autoimune/sangue , Hepatite Autoimune/imunologia , Humanos , Imunoglobulina G/sangue , Imunoglobulina G/genética , Imunoglobulina G/imunologia , Masculino , Exposição Ocupacional/efeitos adversos , Polimorfismo Genético , Tricloroetileno/imunologia , Tricloroetileno/toxicidade
7.
Front Endocrinol (Lausanne) ; 13: 835054, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35528000

RESUMO

Background and Aims: The NLRP3 gene is reportedly associated with several autoimmune diseases. However, in the Chinese Han population, whether NLRP3 polymorphisms are associated with type 1 diabetes (T1D) is unclear. Therefore, this study examined the associations of rs3806265 and rs4612666 of the NLRP3 gene with T1D susceptibility and the clinical characteristics of Chinese Han T1D patients. Methods: In total, 510 classic T1D patients and 531 healthy controls from the Chinese Han population were recruited for a case-control study. rs3806265 and rs4612666 of the NLRP3 gene were genotyped by MassARRAY. Logistic regression analysis and the chi-square test were used to compare the distributions of the alleles and genotypes of rs3806265 and rs4612666. The relationships between rs3806265 and rs4612666 and the clinical characteristics of T1D patients were analyzed by Kruskal-Wallis one-way ANOVA. Student's t test was used to analyze normally distributed data. Bonferroni correction was used for multiple comparisons. Results: 1) rs3806265 was associated with glutamic acid decarboxylase antibody (GADA) titers (P = 0.02), and patients with the CC genotype had higher GADA titers than patients with the TT genotype. 2) rs4612666 was also associated with GADA titers (P=0.041). Compared with patients with the CC genotype, patients with the TT genotype had higher GADA titers. 3) rs3806265 and rs4612666 of the NLRP3 gene were not significantly associated with T1D susceptibility under different genetic models. Conclusion: rs3806265 and rs4612666 of the NLRP3 gene were significantly associated with GADA titers in Chinese Han T1D patients.


Assuntos
Autoanticorpos , Diabetes Mellitus Tipo 1 , Proteína 3 que Contém Domínio de Pirina da Família NLR , Anticorpos , Autoanticorpos/sangue , Estudos de Casos e Controles , Diabetes Mellitus Tipo 1/genética , Predisposição Genética para Doença , Glutamato Descarboxilase/imunologia , Humanos , Proteína 3 que Contém Domínio de Pirina da Família NLR/genética , Polimorfismo de Nucleotídeo Único
8.
BMC Neurol ; 22(1): 185, 2022 May 18.
Artigo em Inglês | MEDLINE | ID: mdl-35585528

RESUMO

BACKGROUND: Since the beginning of the COVID-19 pandemic and development of new vaccines, the issue of post-vaccination exacerbation or manifestation of demyelinating central nervous system (CNS) disorders has gained increasing attention. CASE PRESENTATION: We present a case of a 68-year-old woman previously diagnosed with multiple sclerosis (MS) since the 1980s who suffered a rapidly progressive severe sensorimotor paraparesis with loss of bladder and bowel control due to an acute longitudinal extensive transverse myelitis (LETM) after immunization with the mRNA Pfizer-BioNTech COVID-19 vaccine. Detection of Aquaporin-4-antibodies (AQP4) in both serum and CSF led to diagnosis of AQP4-antibody positive neuromyelitis optica spectrum disorder (NMOSD). Treatment with intravenous corticosteroids and plasmapheresis led to a slight improvement of the patient's symptoms. CONCLUSIONS: Pathogenic mechanisms of post-vaccination occurrence of NMOSD are still unknown. However, cases like this should make aware of rare neurological disorders manifesting after vaccination and potentially contribute to improvement of management of vaccinating patients with inflammatory CNS disorders in the future. So far two cases of AQP4-antibody positive NMOSD have been reported in association with viral vector COVID-19 vaccines. To our knowledge, we report the first case of AQP4-antibody positive NMOSD after immunization with an mRNA COVID-19-vaccine.


Assuntos
Vacina BNT162 , COVID-19 , Esclerose Múltipla , Mielite Transversa , Neuromielite Óptica , Idoso , Aquaporina 4/sangue , Aquaporina 4/líquido cefalorraquidiano , Autoanticorpos/sangue , Autoanticorpos/líquido cefalorraquidiano , Vacina BNT162/efeitos adversos , Vacina BNT162/uso terapêutico , COVID-19/prevenção & controle , Vacinas contra COVID-19/efeitos adversos , Vacinas contra COVID-19/uso terapêutico , Progressão da Doença , Feminino , Humanos , Esclerose Múltipla/sangue , Esclerose Múltipla/líquido cefalorraquidiano , Esclerose Múltipla/complicações , Mielite Transversa/induzido quimicamente , Mielite Transversa/diagnóstico , Mielite Transversa/etiologia , Neuromielite Óptica/sangue , Neuromielite Óptica/líquido cefalorraquidiano , Neuromielite Óptica/diagnóstico , Neuromielite Óptica/etiologia , Pandemias , RNA Mensageiro , Vacinação/efeitos adversos
9.
Eur J Neurol ; 29(8): 2376-2385, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35514068

RESUMO

BACKGROUND AND PURPOSE: Faciobrachial dystonic seizures (FBDS) and hyponatremia are the distinct clinical features of autoimmune encephalitis (AE) caused by antibodies against leucine-rich glioma-inactivated 1 (LGI1). The present study aims to explore the pathophysiological patterns and neural mechanisms underlying these symptoms. METHODS: We included 30 patients with anti-LGI1 AE and 30 controls from a retrospective observational cohort. Whole-brain metabolic pattern analysis was performed to assess the pathological network of anti-LGI1 AE, as well as the symptom networks associated with FBDS. Logistic regression was applied to explore independent predictors of FBDS. Finally, we used a multiple regression model to investigate the hyponatremia-associated brain network and its effect on serum sodium levels. RESULTS: The pathological network of anti-LGI1 AE involved hypermetabolism in the cerebellum, subcortical structures and Rolandic area, as well as hypometabolism in the medial prefrontal cortex. The symptom network of FBDS included hypometabolism in the cerebellum and Rolandic area (pFDR <0.05). Hypometabolism in the cerebellum was an independent predictor of FBDS (p < 0.001). Hyponatremia-associated network highlighted a negative effect on the caudate nucleus, frontal and temporal white matter. The metabolism of the hypothalamus was negatively associated with (Pearson's R = -0.180, p = 0.342), while not the independent predictor for serum sodium level (path c' = -7.238, 95% confidence interval = -30.947 to 16.472). CONCLUSIONS: Our results provide insights into the whole-brain metabolic patterns of patients with anti-LGI1 AE, including the symptom network associated with FBDS and the hyponatremia-associated brain network. The findings help us to understand the neural mechanisms underlying anti-LGI1 AE and to evaluate the progress of this disease.


Assuntos
Doenças Autoimunes , Encéfalo , Encefalite Límbica , Autoanticorpos/sangue , Doenças Autoimunes/complicações , Doenças Autoimunes/metabolismo , Encéfalo/metabolismo , Humanos , Hiponatremia/etiologia , Hiponatremia/metabolismo , Peptídeos e Proteínas de Sinalização Intracelular/imunologia , Encefalite Límbica/complicações , Encefalite Límbica/metabolismo , Estudos Retrospectivos , Convulsões/etiologia , Convulsões/metabolismo , Sódio/sangue
10.
Proc Natl Acad Sci U S A ; 119(21): e2200413119, 2022 05 24.
Artigo em Inglês | MEDLINE | ID: mdl-35576468

RESUMO

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection fatality rate (IFR) doubles with every 5 y of age from childhood onward. Circulating autoantibodies neutralizing IFN-α, IFN-ω, and/or IFN-ß are found in ∼20% of deceased patients across age groups, and in ∼1% of individuals aged <70 y and in >4% of those >70 y old in the general population. With a sample of 1,261 unvaccinated deceased patients and 34,159 individuals of the general population sampled before the pandemic, we estimated both IFR and relative risk of death (RRD) across age groups for individuals carrying autoantibodies neutralizing type I IFNs, relative to noncarriers. The RRD associated with any combination of autoantibodies was higher in subjects under 70 y old. For autoantibodies neutralizing IFN-α2 or IFN-ω, the RRDs were 17.0 (95% CI: 11.7 to 24.7) and 5.8 (4.5 to 7.4) for individuals <70 y and ≥70 y old, respectively, whereas, for autoantibodies neutralizing both molecules, the RRDs were 188.3 (44.8 to 774.4) and 7.2 (5.0 to 10.3), respectively. In contrast, IFRs increased with age, ranging from 0.17% (0.12 to 0.31) for individuals <40 y old to 26.7% (20.3 to 35.2) for those ≥80 y old for autoantibodies neutralizing IFN-α2 or IFN-ω, and from 0.84% (0.31 to 8.28) to 40.5% (27.82 to 61.20) for autoantibodies neutralizing both. Autoantibodies against type I IFNs increase IFRs, and are associated with high RRDs, especially when neutralizing both IFN-α2 and IFN-ω. Remarkably, IFRs increase with age, whereas RRDs decrease with age. Autoimmunity to type I IFNs is a strong and common predictor of COVID-19 death.


Assuntos
Anticorpos Neutralizantes , Autoanticorpos , Autoimunidade , COVID-19 , Interferon Tipo I , SARS-CoV-2 , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Anticorpos Neutralizantes/sangue , Autoanticorpos/sangue , COVID-19/imunologia , COVID-19/mortalidade , Feminino , Humanos , Interferon Tipo I/imunologia , Masculino , Pessoa de Meia-Idade , Risco
11.
Eur J Neurol ; 29(8): 2367-2375, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35488492

RESUMO

BACKGROUND AND PURPOSE: This study was undertaken to investigate the association between human leukocyte antigen (HLA) genotype and clinical characteristics of anti-LGI1 encephalitis. METHODS: HLA genotyping was performed in 34 patients with anti-LGI1 encephalitis admitted to West China Hospital between April 2014 and May 2021, as well as in 305 healthy controls. The online tool NetMHCIIpan 4.0 and AutoDock Vina software were used to predict binding between LGI1 peptide and HLA class II molecules. RESULTS: Risk of anti-LGI1 encephalitis was strongly associated with the DRB1*03:01 allele (odds ratio [OR] = 4.31, 95% confidence interval [CI] = 1.96-9.25, corrected p = 2.75 × 10-4 ) and the DRB1*03:01-DQB1*02:01 haplotype (OR = 4.45, 95% CI = 2.02-9.59, corrected p = 2.94 × 10-4 ). Compared to carriers of the DRB1*07:01 allele, those with the DRB1*03:01 allele were more likely to be female (93.3% vs. 33.3%, p = 0.004) and to be younger (median age = 38 vs. 65 years, p < 0.001). DRB1*03:01 carriers showed stronger response to immunotherapy than carriers of the DRB1*07:01 allele, based on median score decrease on the modified Rankin scale (2, interquartile range = 1-2 vs. 1, interquartile range = 0-1; p = 0.03) at 4 weeks after immunotherapy. Prediction and docking algorithms suggested that the LGI1 peptide can bind to the DRB1*03:01 molecule strongly. CONCLUSIONS: The strong association between anti-LGI1 encephalitis and certain HLA class II alleles supports a primary autoimmune origin for the disease. Carriers of the DRB1*03:01 allele in Chinese patients with anti-LGI1 encephalitis are more likely to be female, to suffer earlier disease onset, and to respond better to immunotherapy.


Assuntos
Doenças Autoimunes , Cadeias HLA-DRB1 , Encefalite Límbica , Adulto , Alelos , Autoanticorpos/sangue , Doenças Autoimunes/genética , Feminino , Frequência do Gene , Predisposição Genética para Doença , Cadeias HLA-DRB1/genética , Haplótipos , Humanos , Encefalite Límbica/genética , Masculino , Fatores Sexuais
12.
Dis Markers ; 2022: 8741058, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35256895

RESUMO

Introduction: Studies have indicated that immune reactions contribute to endothelial dysfunction and atherosclerosis. It is unclear whether thyroid dysfunction or elevated thyroid autoantibodies are associated with atherosclerosis. Therefore, we investigated the influence of thyroid autoimmunity related to elevated thyroid autoantibodies on functional outcome in euthyroidism with acute ischemic stroke (AIS). Methods: All patients with AIS underwent tests for thyroid function and thyroid antibodies (thyroid peroxidase antibody and thyroglobulin autoantibody). We divided the patients suffering from euthyroidism and AIS into positive thyroid autoantibody and negative thyroid autoantibody groups. Demographic profiles, risk factors, and functional outcomes were compared between the two groups. Results: Out of the total 422 patients, 50 (11.8%) were included in the positive thyroid autoantibody group. The National Institutes of Health Stroke Scale (NIHSS) score at admission and discharge was higher in the positive thyroid autoantibody group than the negative thyroid autoantibody group (P < 0.05). In addition, there was significant difference in the mortality during hospitalizations between the two groups (P < 0.01). Conclusion: This study showed that thyroid autoantibodies aggravate stroke severity in euthyroidism with AIS. We speculate that vascular damage related to thyroid autoimmunity may aggravate the increased risk of unfavorable outcomes, independent of thyroid function.


Assuntos
Autoanticorpos/sangue , Síndromes do Eutireóideo Doente/imunologia , Iodeto Peroxidase/imunologia , AVC Isquêmico/imunologia , Gravidade do Paciente , Tireoglobulina/imunologia , Doença Aguda , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Síndromes do Eutireóideo Doente/sangue , Síndromes do Eutireóideo Doente/complicações , Síndromes do Eutireóideo Doente/fisiopatologia , Feminino , Humanos , AVC Isquêmico/sangue , AVC Isquêmico/complicações , AVC Isquêmico/fisiopatologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
13.
Horm Metab Res ; 54(3): 153-161, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35276740

RESUMO

SARS-CoV-2 may affect the hypothalamic-pituitary axis and pituitary dysfunction may occur. Therefore, we investigated neuroendocrine changes, in particular, secondary adrenal insufficiency, using a dynamic test and the role of autoimmunity in pituitary dysfunction in patients with COVID-19. The single-center, prospective, case-control study included patients with polymerase chain reaction (PCR)-confirmed COVID-19 and healthy controls. Basal hormone levels were measured, and the adrenocorticotropic hormone (ACTH) stimulation test was performed. Antipituitary (APA) and antihypothalamic antibodies (AHA) were also determined. We examined a total of 49 patients with COVID-19 and 28 healthy controls. The frequency of adrenal insufficiency in patients with COVID-19 was found as 8.2%. Patients with COVID-19 had lower free T3, IGF-1, and total testosterone levels, and higher cortisol and prolactin levels when compared with controls. We also demonstrated the presence of APA in three and AHA in one of four patients with adrenal insufficiency. In conclusion, COVID-19 may result in adrenal insufficiency, thus routine screening of adrenal functions in these patients is needed. Endocrine disturbances in COVID-19 are similar to those seen in acute stressful conditions or infections. Pituitary or hypothalamic autoimmunity may play a role in neuroendocrine abnormalities in COVID-19.


Assuntos
Hormônio Adrenocorticotrópico/sangue , COVID-19/imunologia , Hipotálamo/imunologia , Hipófise/imunologia , Adulto , Autoanticorpos/sangue , Autoimunidade , COVID-19/sangue , COVID-19/metabolismo , COVID-19/virologia , Estudos de Casos e Controles , Feminino , Humanos , Hidrocortisona/sangue , Hipotálamo/metabolismo , Fator de Crescimento Insulin-Like I/metabolismo , Masculino , Pessoa de Meia-Idade , Hipófise/metabolismo , Prolactina/sangue , Estudos Prospectivos , SARS-CoV-2/fisiologia , Testosterona/sangue
14.
Front Endocrinol (Lausanne) ; 13: 840668, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35273575

RESUMO

Background: This is the first study, that aimed: a) to compare immune response, namely the kinetics of neutralizing antibodies (Nabs), after vaccination with BNT162b2 mRNA vaccine (Comirnaty, Pfizer/BioNTech) between patients with autoimmune thyroiditis and controls, and b) to investigate changes in thyroid function in healthy subjects with no history of thyroid dysfunction before and after vaccination with BNT162b2 mRNA vaccine (Comirnaty, Pfizer/BioNTech). Methods: The entire study consisted of two sub-studies. In the first sub-study, NAbs levels after BNT162b2 mRNA vaccination were compared between 56 patients with autoimmune thyroiditis and 56 age and gender-matched healthy controls from the day of the first dose until a period of up to three months after the second dose. In the second sub-study, thyroid hormones (T3, T4, TSH) and thyroid auto-antibodies levels (anti-TG, anti-TPO) of 72 healthy subjects with no history of thyroid disease were examined before (D1) and one month after completion of the second dose (D50). Results: Among patients with autoimmune thyroiditis, the median neutralizing inhibition on D22, immediately before second dose, was 62.5%. One month later (D50), values increased to 96.7%, while three months after the second dose NAbs titers remained almost the same (94.5%). In the healthy group, median NAbs levels at D22 were 53.6%. On D50 the median inhibition values increased to 95.1%, while after three months they were 89.2%. The statistical analysis did not show significant differences between two groups (p-values 0.164, 0.390, 0.105 for D22, D50 and three months). Regarding changes in thyroid function, the mean value for T4 before vaccination was 89.797 nmol/L and one month after the second dose was 89.11 nmol/L (p-value=0.649). On D1 the mean T3 value was 1.464 nmol/L, which dropped to 1.389 nmol/L on D50 (p-value = 0.004). For TSH, mean levels were 2.064 mIU/ml on D1 and fell to 1.840 mIU/ml one month after the second dose (p-value=0.037). Despite decrease, all thyroid hormone levels remained within the normal range. No changes were found for anti-TPO or anti-TG. Conclusions: This study provided evidence that patients with autoimmune thyroiditis present similar immunological response to COVID-19 BNT162b2 mRNA vaccine (Comirnaty, Pfizer/BioNTech) with healthy subjects, while vaccination may affect thyroid function.


Assuntos
Anticorpos Neutralizantes/imunologia , Anticorpos Antivirais/imunologia , COVID-19/imunologia , SARS-CoV-2/imunologia , Tireoidite Autoimune/imunologia , Adulto , Autoanticorpos/sangue , Autoanticorpos/imunologia , /genética , COVID-19/prevenção & controle , COVID-19/virologia , Estudos de Casos e Controles , Feminino , Seguimentos , Voluntários Saudáveis , Humanos , Masculino , Pessoa de Meia-Idade , SARS-CoV-2/genética , Glândula Tireoide/metabolismo , Hormônios Tireóideos/sangue , Hormônios Tireóideos/metabolismo , Tireoidite Autoimune/metabolismo , Vacinação
15.
Ren Fail ; 44(1): 428-433, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-35272568

RESUMO

OBJECTIVES: Idiopathic membranous nephropathy (iMN) is a major cause of nephrotic syndrome. Atypical membranous nephropathy (aMN) is a new type of nephropathy in China, characterized by a 'full-house' on immunofluorescent examination, that is IgG, IgA, IgM, C3, C1q positive, but without clinical evidence of a secondary cause. Phospholipase A2 receptor (PLA2R) was the major target antigens in iMN patients. Activation of the mannose-binding lectin (MBL) pathway plays a vital role in the development of MN. Our objective was to investigate the role of PLA2R and MBL in the pathogenesis of iMN and aMN. METHODS: We conducted a retrospective observational study using propensity score matching by age, gender, and eGFR. All clinical, laboratory data, and follow-up data of the patients were collected. Serum levels of anti-PLA2R antibodies and MBL were tested. RESULTS: Finally, 30 iMN patients and 30 aMN patients were included, and 20 healthy controls were retrospectively collected in this study. The 24 h proteinuria level was higher and serum albumin was lower in anti-PLA2R (+) patients than in anti-PLA2R (-) patients in both iMN and aMN groups. In aMN patients, MBL levels were significantly higher in anti-PLA2R (+) patients than in anti-PLA2R (-) patients (p = .045). The serum level of anti-PLA2R positively correlated with no-remission in both iMN and aMN groups. CONCLUSIONS: The complement lectin pathway has an association with the development of MN, especially in patients with positive anti-PLA2R antibodies. Serum MBL cannot differentiate between the two diseases. Serum MBL levels are not associated with clinical manifestations, nor with prognosis.


Assuntos
Autoanticorpos/sangue , Glomerulonefrite Membranosa/imunologia , Lectina de Ligação a Manose/sangue , Receptores da Fosfolipase A2/imunologia , Adulto , Idoso , Feminino , Glomerulonefrite Membranosa/sangue , Humanos , Rim/metabolismo , Rim/patologia , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Pontuação de Propensão , Receptores da Fosfolipase A2/genética , Estudos Retrospectivos
16.
J Korean Med Sci ; 37(10): e75, 2022 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-35289136

RESUMO

Vaccine-induced immune thrombotic thrombocytopenia (VITT) is a rare but life-threatening complication. VITT strongly mimics heparin-induced thrombocytopenia (HIT) and shares clinical features. Heparin is commonly used to prevent coagulation during hemodialysis. Therefore, nephrologists might encounter patients needing dialysis with a history of heparin exposure who developed thrombotic thrombocytopenia after vaccination. A 70-year-old male presented with acute kidney injury and altered mental status due to lithium intoxication. He needed consecutive hemodialysis using heparin. Deep vein thrombosis of left lower extremity and accompanying severe thrombocytopenia of 15,000/µL on 24 days after vaccination and at the same time, nine days after heparin use. Anti-platelet factor 4 antibody test was positive. Anticoagulation with apixaban and intravenous immunoglobulin (IVIG) infusion resolved swelling of his left calf and thrombocytopenia. There were no definitive diagnostic tools capable of differentiating between VITT and HIT in this patient. Although VITT and HIT share treatment with IVIG and non-heparin anticoagulation, distinguishing between VITT and HIT will make it possible to establish a follow-up vaccination plan in a person who has had a thrombocytopenic thrombotic event. Further research is needed to develop the tools to make a clear distinction between the clinical syndromes.


Assuntos
/efeitos adversos , Heparina/efeitos adversos , Púrpura Trombocitopênica Idiopática/etiologia , Diálise Renal/efeitos adversos , Trombocitopenia/etiologia , Idoso , Anticoagulantes/efeitos adversos , Autoanticorpos/sangue , Diagnóstico Diferencial , Humanos , Imunoglobulina G/sangue , Lítio/toxicidade , Masculino , Contagem de Plaquetas , Fator Plaquetário 4/imunologia , Púrpura Trombocitopênica Idiopática/sangue , Púrpura Trombocitopênica Idiopática/diagnóstico , Diálise Renal/métodos , Trombocitopenia/sangue , Trombocitopenia/diagnóstico
17.
Dis Markers ; 2022: 6657820, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35273656

RESUMO

Purpose: This study is aimed at evaluating serum autoantibodies against four tumor-associated antigens, including LRDD, STC1, FOXA1, and EDNRB, as biomarkers in the immunodiagnosis of ovarian cancer (OC). Methods: The autoantibodies against LRDD, STC1, FOXA1, and EDNRB were measured using an enzyme-linked immunosorbent assay (ELISA) in 94 OC patients and 94 normal healthy controls (NHC) in the research group. In addition, the diagnostic values of different autoantibodies were validated in another independent validation group, which comprised 136 OC patients, 136 NHC, and 181 patients with benign ovarian diseases (BOD). Results: In the research group, autoantibodies against LRDD, STC1, and FOXA1 had higher serum titer in OC patients than NHC (P < 0.001). The area under receiver operating characteristic curves (AUCs) of these three autoantibodies were 0.910, 0.879, and 0.817, respectively. In the validation group, they showed AUCs of 0.759, 0.762, and 0.817 and sensitivities of 49.3%, 42.7%, and 48.5%, respectively, at specificity over 90% for discriminating OC patients from NHC. For discriminating OC patients from BOD, they showed AUCs of 0.718, 0.729, and 0.814 and sensitivities of 47.1%, 39.0%, and 51.5%, respectively, at specificity over 90%. The parallel analyses demonstrated that the combination of anti-LRDD and anti-FOXA1 autoantibodies achieved the optimal diagnostic performance with the sensitivity of 58.1% at 87.5% specificity and accuracy of 72.8%. The positive rate of the optimal autoantibody panel improved from 62.4% to 87.1% when combined with CA125 in detecting OC patients. Conclusion: Serum autoantibodies against LRDD, STC1, and FOXA1 have potential diagnostic values in detecting OC.


Assuntos
Autoanticorpos/sangue , Biomarcadores Tumorais/sangue , Proteínas Adaptadoras de Sinalização de Receptores de Domínio de Morte/imunologia , Fator 3-alfa Nuclear de Hepatócito/imunologia , Neoplasias Ovarianas/sangue , Neoplasias Ovarianas/diagnóstico , Receptores de Superfície Celular/imunologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Pessoa de Meia-Idade , Neoplasias Ovarianas/imunologia , Estudos Retrospectivos , Adulto Jovem
18.
Nat Commun ; 13(1): 1220, 2022 03 09.
Artigo em Inglês | MEDLINE | ID: mdl-35264564

RESUMO

COVID-19 shares the feature of autoantibody production with systemic autoimmune diseases. In order to understand the role of these immune globulins in the pathogenesis of the disease, it is important to explore the autoantibody spectra. Here we show, by a cross-sectional study of 246 individuals, that autoantibodies targeting G protein-coupled receptors (GPCR) and RAS-related molecules associate with the clinical severity of COVID-19. Patients with moderate and severe disease are characterized by higher autoantibody levels than healthy controls and those with mild COVID-19 disease. Among the anti-GPCR autoantibodies, machine learning classification identifies the chemokine receptor CXCR3 and the RAS-related molecule AGTR1 as targets for antibodies with the strongest association to disease severity. Besides antibody levels, autoantibody network signatures are also changing in patients with intermediate or high disease severity. Although our current and previous studies identify anti-GPCR antibodies as natural components of human biology, their production is deregulated in COVID-19 and their level and pattern alterations might predict COVID-19 disease severity.


Assuntos
Autoanticorpos/imunologia , COVID-19/imunologia , Receptores Acoplados a Proteínas G/imunologia , Sistema Renina-Angiotensina/imunologia , Autoanticorpos/sangue , Autoimunidade , Biomarcadores/sangue , COVID-19/sangue , COVID-19/classificação , Estudos Transversais , Feminino , Humanos , Aprendizado de Máquina , Masculino , Análise Multivariada , Receptor Tipo 1 de Angiotensina/imunologia , Receptores CXCR3/imunologia , SARS-CoV-2 , Índice de Gravidade de Doença
19.
Lab Med ; 53(4): 426-432, 2022 Jul 04.
Artigo em Inglês | MEDLINE | ID: mdl-35311959

RESUMO

OBJECTIVE: The absence of specific markers can make the diagnosis of neuroimmune disorders difficult, making other biomarkers such as thyroid peroxidase antibodies (TPO-Abs) more relevant. Laboratory tests are susceptible to interference, especially those tests performed using immunoassay techniques. The effect of treatment with human intravenous immunoglobulin (IVIG) on the results of TPO-Abs assays has not been previously characterized. MATERIALS AND METHODS: We analyzed TPO-Abs levels in 170 children monitored in the neuroimmune disease department of a tertiary hospital. We analyzed the characteristics of patients with increased TPO-Abs values and compared their progress with and without treatment. RESULTS: We found that 97% of patients with elevated TPO-Abs had received IVIG. After withdrawal from IVIG, a mean TPO-Abs decrease of 62.5% at 1 month was observed. The IVIG drug preparation was found to contain 1176 U/mL of TPO-Abs. An interferogram confirmed interference. CONCLUSION: It is advisable to measure levels of TPO-Abs before starting immunotherapy and remain vigilant regarding possible interference in the event of unsubstantiated elevations of this analyte.


Assuntos
Autoanticorpos , Imunoglobulinas Intravenosas , Iodeto Peroxidase , Doenças Neuroinflamatórias , Autoanticorpos/sangue , Biomarcadores/sangue , Criança , Humanos , Imunoglobulinas Intravenosas/uso terapêutico , Iodeto Peroxidase/imunologia , Doenças Neuroinflamatórias/diagnóstico , Doenças Neuroinflamatórias/terapia
20.
Anticancer Res ; 42(3): 1517-1526, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35220247

RESUMO

BACKGROUND/AIM: To estimate the prevalence of autoimmune atrophic gastritis (AAG) in the Russian Federation, a systematic screening of asymptomatic healthy adults by non-invasive biomarker testing was conducted. The aim was i) To test the validity of non-invasive serological screening for AAG; ii) to establish the prevalence of AAG among asymptomatic adults. PATIENTS AND METHODS: Altogether, 1,283 asymptomatic, healthy adults (mean age: 38 years) were screened by GastroPanel® test. Those with a biomarker profile indicating AG (n=46) were invited for further examinations; 21 consented to gastroscopy with biopsies classified using the Updated Sydney System and Operative Link to Gastric Atrophy. Blood tests included parietal cell, intrinsic factor and thyroid peroxidase antibodies, and analysis of vitamin B12 and iron. RESULTS: Gastroscopy and biopsies confirmed AG in 20 of the individuals. Parietal cell, intrinsic factor and thyroid peroxidase antibodies were present in five, one and eight individuals, respectively. AAG-associated co-morbidities (iron deficiency and pernicious anemia) were diagnosed in 10 out of 21. The final diagnosis of AAG was made in 15 out of 1,283 subjects (1.2%), of whom four were Helicobacter pylori-positive. When corrected for verification bias (non-attendees in the confirmatory tests; n=25), the adjusted prevalence of AAG was 2.6% (33/1,283). CONCLUSION: AAG prevalence of 2.6% is among the highest reported using non-invasive tests. GastroPanel® is an optimal screening tool, providing the first link in the diagnostic protocol leading to the final diagnosis of this condition. The role of Helicobacter pylori as a trigger of AAG cannot be ruled out.


Assuntos
Autoanticorpos/sangue , Doenças Autoimunes/diagnóstico , Gastrite Atrófica/diagnóstico , Testes Sorológicos , Adulto , Idoso , Doenças Assintomáticas , Doenças Autoimunes/sangue , Doenças Autoimunes/epidemiologia , Doenças Autoimunes/patologia , Biomarcadores/sangue , Biópsia , Ensaio de Imunoadsorção Enzimática , Feminino , Gastrite Atrófica/sangue , Gastrite Atrófica/epidemiologia , Gastrite Atrófica/patologia , Gastroscopia , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prevalência , Federação Russa/epidemiologia , Adulto Jovem
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...