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1.
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
2.
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
3.
Clin Immunol ; 230: 108819, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34358691

RESUMO

Acquired angioedema due to C1 inhibitor deficiency (C1-INH-AAE) is a rare disease characterized by adult-onset recurrent non-urticarial angioedema with low levels of C1-INH. It is associated with lymphoproliferative disorders, and treatments are off-label with variable success. We conducted a systematic literature review to include patients with C1-INH-AAE identified in PubMed and Embase databases between January 2006 and February 2021. Clinical features of these patients were summarized, and factors associated with disease remission were explored. A total of 121 patients were included in the current study with a median age at diagnosis of 64 years and 45.5% being male. An associated disease was recorded in 94 patients (77.7%), and lymphoproliferative disorder was the most reported (59/94, 62.8%). Anti-C1-INH autoantibodies were present in 45 of 71 patients (63.4%). Factors impacting disease remissions included age (odds ratio [OR] 0.951, 95% confidence interval [CI] 0.909-0.994, p = 0.027), male (OR 0.327, 95% CI 0.124-0.866, p = 0.025), presence of monoclonal gammopathy (OR 0.133, 95% CI 0.041-0.429, p = 0.001), requirement of specific on-demand treatment (OR 0.216, 95% CI 0.066-0.709, p = 0.012) and rituximab use (OR 2.865, 95% CI 1.038-7.911, p = 0.042). A total of nine patients (7.4%) died at last follow up and most were unrelated to C1-INH-AAE. Our results imply that C1-INH-AAE is primarily associated with underlying B or plasma cell abnormalities, and clone-directed therapies could be promising options for its long-term management.


Assuntos
Angioedema/etiologia , Proteína Inibidora do Complemento C1/metabolismo , Complemento C1/antagonistas & inibidores , Idoso , Angioedema/imunologia , Angioedema/terapia , Autoanticorpos/sangue , Proteína Inibidora do Complemento C1/imunologia , Proteína Inibidora do Complemento C1/uso terapêutico , Feminino , Humanos , Transtornos Linfoproliferativos/complicações , Masculino , Pessoa de Meia-Idade , Paraproteinemias/complicações , Resultado do Tratamento
4.
Adv Clin Chem ; 104: 299-340, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34462057

RESUMO

Cryoglobulins consist of serum immunoglobulins that precipitate below 37°C and resolubilize upon warming. The clinical triad of cryoglobulinemia usually includes purpura, weakness, and arthralgia. Cryoglobulinemic syndrome, clinically defined as a systemic vasculitis, is associated with chronic infection with hepatitis C virus (HCV) and autoimmune disorders and can evolve into B-cell malignancies. While the current literature about HCV-associated cryoglobulinemia is not very limited, little is known about the immunologic and serologic profiles of affected patients. Therefore, comprehension of the pathogenetic mechanisms underlying cryoprecipitation could be very helpful. Due to the persistence of viral antigenic stimulation, biomarkers to use after the worsening progression of HCV infection to lymphoproliferative and/or autoimmune diseases are widely needed. Laboratory methods used to detect and characterize low concentrations of cryoprecipitates and immunotyping patterns could improve patient management. The most critical factor affecting cryoglobulin testing is that the pre-analytical phase is not fully completed at 37°C.


Assuntos
Biomarcadores/sangue , COVID-19/complicações , Crioglobulinemia/sangue , Crioglobulinas/análise , Hepatite C/fisiopatologia , Animais , Autoanticorpos/sangue , Precipitação Química , Crioglobulinemia/terapia , Crioglobulinas/química , Hepatite C/sangue , Humanos , Vasculite/virologia
5.
Viruses ; 13(8)2021 08 11.
Artigo em Inglês | MEDLINE | ID: mdl-34452459

RESUMO

COVID-19 convalescent plasma (CCP) is currently under investigation for both treatment and post-exposure prophylaxis. The active component of CCP mediating improved outcome is commonly reported as specific antibodies, particularly neutralizing antibodies, with clinical efficacy characterized according to the level or antibody affinity. In this review, we highlight the potential role of additional factors in CCP that can be either beneficial (e.g., AT-III, alpha-1 AT, ACE2+ extracellular vesicles) or detrimental (e.g., anti-ADAMTS13, anti-MDA5 or anti-interferon autoantibodies, pro-coagulant extracellular vesicles). Variations in these factors in CCP may contribute to varied outcomes in patients with COVID-19 and undergoing CCP therapy. We advise careful, retrospective investigation of such co-factors in randomized clinical trials that use fresh frozen plasma in control arms. Nevertheless, it might be difficult to establish a causal link between these components and outcome, given that CCP is generally safe and neutralizing antibody effects may predominate.


Assuntos
Anticorpos Neutralizantes/sangue , Anticorpos Antivirais/sangue , COVID-19/terapia , SARS-CoV-2/imunologia , Anti-Inflamatórios/sangue , Anticorpos Neutralizantes/uso terapêutico , Anticorpos Antivirais/uso terapêutico , Autoanticorpos/sangue , Inibidores dos Fatores de Coagulação Sanguínea/sangue , Fatores de Coagulação Sanguínea/análise , Reações Cruzadas , Vesículas Extracelulares , Humanos , Imunização Passiva/efeitos adversos , Fatores Imunológicos/sangue , Imunossupressores/sangue
6.
Lancet Neurol ; 20(9): 762-772, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34418402

RESUMO

Myelin-oligodendrocyte glycoprotein antibody-associated disease (MOGAD) is a recently identified autoimmune disorder that presents in both adults and children as CNS demyelination. Although there are clinical phenotypic overlaps between MOGAD, multiple sclerosis, and aquaporin-4 antibody-associated neuromyelitis optica spectrum disorder (NMOSD) cumulative biological, clinical, and pathological evidence discriminates between these conditions. Patients should not be diagnosed with multiple sclerosis or NMOSD if they have anti-MOG antibodies in their serum. However, many questions related to the clinical characterisation of MOGAD and pathogenetic role of MOG antibodies are still unanswered. Furthermore, therapy is mainly based on standard protocols for aquaporin-4 antibody-associated NMOSD and multiple sclerosis, and more evidence is needed regarding how and when to treat patients with MOGAD.


Assuntos
Autoanticorpos/sangue , Doenças Autoimunes Desmielinizantes do Sistema Nervoso Central/diagnóstico , Glicoproteína Mielina-Oligodendrócito/imunologia , Adolescente , Adulto , Biomarcadores , Criança , Doenças Autoimunes Desmielinizantes do Sistema Nervoso Central/imunologia , Doenças Autoimunes Desmielinizantes do Sistema Nervoso Central/patologia , Doenças Autoimunes Desmielinizantes do Sistema Nervoso Central/fisiopatologia , Humanos , Fatores Imunológicos/farmacologia , Pessoa de Meia-Idade , Adulto Jovem
7.
J Exp Med ; 218(10)2021 10 04.
Artigo em Inglês | MEDLINE | ID: mdl-34357402

RESUMO

IFN-I and IFN-III immunity in the nasal mucosa is poorly characterized during SARS-CoV-2 infection. We analyze the nasal IFN-I/III signature, namely the expression of ISGF-3-dependent IFN-stimulated genes, in mildly symptomatic COVID-19 patients and show its correlation with serum IFN-α2 levels, which peak at symptom onset and return to baseline from day 10 onward. Moreover, the nasal IFN-I/III signature correlates with the nasopharyngeal viral load and is associated with the presence of infectious viruses. By contrast, we observe low nasal IFN-I/III scores despite high nasal viral loads in a subset of critically ill COVID-19 patients, which correlates with the presence of autoantibodies (auto-Abs) against IFN-I in both blood and nasopharyngeal mucosa. In addition, functional assays in a reconstituted human airway epithelium model of SARS-CoV-2 infection confirm the role of such auto-Abs in abrogating the antiviral effects of IFN-I, but not those of IFN-III. Thus, IFN-I auto-Abs may compromise not only systemic but also local antiviral IFN-I immunity at the early stages of SARS-CoV-2 infection.


Assuntos
Autoanticorpos/imunologia , COVID-19/imunologia , Interferon Tipo I/imunologia , SARS-CoV-2/imunologia , Adulto , Idoso , Animais , Antivirais/imunologia , Antivirais/farmacologia , Autoanticorpos/sangue , COVID-19/sangue , COVID-19/virologia , Chlorocebus aethiops , Feminino , Humanos , Interferon Tipo I/farmacologia , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Cavidade Nasal/imunologia , Cavidade Nasal/virologia , Estudos Prospectivos , SARS-CoV-2/fisiologia , Células Vero , Carga Viral/efeitos dos fármacos , Carga Viral/imunologia , Replicação Viral/efeitos dos fármacos , Replicação Viral/imunologia
8.
Medicine (Baltimore) ; 100(29): e26654, 2021 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-34398024

RESUMO

RATIONALE: Anti leucine-rich glioma inactivated 1 (LGI1) limbic encephalitis (LE) is rare autoimmune encephalitis, characterized by acute or subacute cognitive impairment, faciobrachial dystonic seizures, mental disorders, and refractory hyponatremia. As a type of treatable rapidly progressive dementia with a good prognosis, early, and accurate diagnosis is essential. We present a case of anti-LGI1 LE who was initially misdiagnosed with Alzheimer disease because his clinical manifestations were similar to Alzheimer disease. PATIENT CONCERNS: A male patient presenting with rapidly progressive dementia, faciobrachial dystonic seizures, psychiatric disturbance, and refractory hyponatremia was admitted. The scores of Mini-Mental State Examination, Montreal Cognitive Assessment, and Neuropsychiatric Inventory were 19/30, 16/30, and 91/144, respectively. Brain magnetic resonance images indicated moderate atrophy of the hippocampus and abnormally hyperintensities in the left medial temporal and hippocampus. DIAGNOSIS: The patient was diagnosed with anti-LGI1 LE based on the presence of LGI-1 antibodies in the cerebrospinal fluid and serum and clinical manifestations. INTERVENTIONS: Patient was treated with glucocorticoid against LGI1, antiepileptic drug, cholinesterase inhibitors, and other adjuvant therapy. OUTCOMES: The patient showed marked improvement on immunotherapy. Clinical symptoms were disappeared and the LGI-1 antibodies in cerebrospinal fluid and serum were both negative at the time of discharge. CONCLUSIONS: Recognition of the specific symptoms and LGI-1 antibody test will be helpful for the early diagnosis, prompt immunotherapy, and good prognosis. This case raises the awareness that rapidly progressive dementia with frequent seizures could be caused by immunoreactions.


Assuntos
Encefalite Límbica/diagnóstico , Idoso , Autoanticorpos/sangue , Autoanticorpos/líquido cefalorraquidiano , Demência/etiologia , Diagnóstico Diferencial , Humanos , Encefalite Límbica/complicações , Encefalite Límbica/diagnóstico por imagem , Encefalite Límbica/imunologia , Imageamento por Ressonância Magnética , Masculino , Convulsões/etiologia
9.
Nat Commun ; 12(1): 4663, 2021 08 02.
Artigo em Inglês | MEDLINE | ID: mdl-34341358

RESUMO

Vaccine-induced thrombotic thrombocytopenia with cerebral venous thrombosis is a syndrome recently described in young adults within two weeks from the first dose of the ChAdOx1 nCoV-19 vaccine. Here we report two cases of malignant middle cerebral artery (MCA) infarct and thrombocytopenia 9-10 days following ChAdOx1 nCoV-19 vaccination. The two cases arrived in our facility around the same time but from different geographical areas, potentially excluding epidemiological links; meanwhile, no abnormality was found in the respective vaccine batches. Patient 1 was a 57-year-old woman who underwent decompressive craniectomy despite two prior, successful mechanical thrombectomies. Patient 2 was a 55-year-old woman who developed a fatal bilateral malignant MCA infarct. Both patients manifested pulmonary and portal vein thrombosis and high level of antibodies to platelet factor 4-polyanion complexes. None of the patients had ever received heparin in the past before stroke onset. Our observations of rare arterial thrombosis may contribute to assessment of possible adverse effects associated with COVID-19 vaccination.


Assuntos
Vacinas contra COVID-19/efeitos adversos , COVID-19/imunologia , Infarto Cerebral/induzido quimicamente , Púrpura Trombocitopênica Idiopática/induzido quimicamente , SARS-CoV-2/imunologia , Trombose/induzido quimicamente , Autoanticorpos/sangue , Autoanticorpos/imunologia , COVID-19/virologia , Vacinas contra COVID-19/administração & dosagem , Vacinas contra COVID-19/imunologia , Infarto Cerebral/diagnóstico por imagem , Angiografia por Tomografia Computadorizada/métodos , Feminino , Humanos , Imageamento por Ressonância Magnética/métodos , Pessoa de Meia-Idade , Fator Plaquetário 4/imunologia , Púrpura Trombocitopênica Idiopática/diagnóstico por imagem , SARS-CoV-2/fisiologia , Trombose/diagnóstico por imagem , Tomografia Computadorizada por Raios X/métodos , Vacinação/efeitos adversos , Trombose Venosa/induzido quimicamente , Trombose Venosa/diagnóstico por imagem
10.
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
11.
Sci Immunol ; 6(62)2021 08 19.
Artigo em Inglês | MEDLINE | ID: mdl-34413139

RESUMO

Circulating autoantibodies (auto-Abs) neutralizing high concentrations (10 ng/mL, in plasma diluted 1 to 10) of IFN-α and/or -ω are found in about 10% of patients with critical COVID-19 pneumonia, but not in subjects with asymptomatic infections. We detect auto-Abs neutralizing 100-fold lower, more physiological, concentrations of IFN-α and/or -ω (100 pg/mL, in 1/10 dilutions of plasma) in 13.6% of 3,595 patients with critical COVID-19, including 21% of 374 patients > 80 years, and 6.5% of 522 patients with severe COVID-19. These antibodies are also detected in 18% of the 1,124 deceased patients (aged 20 days-99 years; mean: 70 years). Moreover, another 1.3% of patients with critical COVID-19 and 0.9% of the deceased patients have auto-Abs neutralizing high concentrations of IFN-ß. We also show, in a sample of 34,159 uninfected subjects from the general population, that auto-Abs neutralizing high concentrations of IFN-α and/or -ω are present in 0.18% of individuals between 18 and 69 years, 1.1% between 70 and 79 years, and 3.4% >80 years. Moreover, the proportion of subjects carrying auto-Abs neutralizing lower concentrations is greater in a subsample of 10,778 uninfected individuals: 1% of individuals <70 years, 2.3% between 70 and 80 years, and 6.3% >80 years. By contrast, auto-Abs neutralizing IFN-ß do not become more frequent with age. Auto-Abs neutralizing type I IFNs predate SARS-CoV-2 infection and sharply increase in prevalence after the age of 70 years. They account for about 20% of both critical COVID-19 cases in the over-80s, and total fatal COVID-19 cases.


Assuntos
Autoanticorpos/imunologia , COVID-19/imunologia , Interferon Tipo I/imunologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Neutralizantes/sangue , Anticorpos Neutralizantes/imunologia , Autoanticorpos/sangue , COVID-19/mortalidade , Estudos de Casos e Controles , Criança , Pré-Escolar , Estado Terminal , Humanos , Imunoglobulina G/sangue , Imunoglobulina G/imunologia , Lactente , Recém-Nascido , Interferon-alfa/imunologia , Pessoa de Meia-Idade , Adulto Jovem
12.
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
13.
Int J Mol Sci ; 22(12)2021 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-34204386

RESUMO

The "Extreme Exercise Hypothesis" states that when individuals perform training beyond the ideal exercise dose, a decline in the beneficial effects of physical activity occurs. This is due to significant changes in myocardial structure and function, such as hemodynamic alterations, cardiac chamber enlargement and hypertrophy, myocardial inflammation, oxidative stress, fibrosis, and conduction changes. In addition, an increased amount of circulating biomarkers of exercise-induced damage has been reported. Although these changes are often reversible, long-lasting cardiac damage may develop after years of intense physical exercise. Since several features of the athlete's heart overlap with arrhythmogenic cardiomyopathy (ACM), the syndrome of "exercise-induced ACM" has been postulated. Thus, the distinction between ACM and the athlete's heart may be challenging. Recently, an autoimmune mechanism has been discovered in ACM patients linked to their characteristic junctional impairment. Since cardiac junctions are similarly impaired by intense physical activity due to the strong myocardial stretching, we propose in the present work the novel hypothesis of an autoimmune response in endurance athletes. This investigation may deepen the knowledge about the pathological remodeling and relative activated mechanisms induced by intense endurance exercise, potentially improving the early recognition of whom is actually at risk.


Assuntos
Atletas , Autoanticorpos/sangue , Biomarcadores/sangue , Resistência Física , Adaptação Fisiológica , Animais , Displasia Arritmogênica Ventricular Direita/etiologia , Displasia Arritmogênica Ventricular Direita/metabolismo , Displasia Arritmogênica Ventricular Direita/fisiopatologia , Autoimunidade , Suscetibilidade a Doenças , Exercício Físico , Humanos , Miocárdio/metabolismo , Miocárdio/patologia , Remodelação Ventricular
14.
BMC Neurol ; 21(1): 274, 2021 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-34243715

RESUMO

BACKGROUND: Ischemic stroke, including transient ischemic attack (TIA) and acute-phase cerebral infarction (aCI), is a serious health problem in the aging society. Thus, this study aimed to identify TIA and aCI biomarkers. METHODS: In 19 patients with TIA, candidate antigens recognized by serum IgG autoantibodies were screened using a human aortic endothelial cell cDNA library. Through amplified luminescent proximity homogeneous assay-linked immunosorbent assay (AlphaLISA), serum antibody levels against the candidate antigens were examined in healthy donor (HD), TIA, and aCI cohorts (n = 285, 92, and 529). The plasma antibody levels in the Japan Public Health Center-based Prospective Cohort Study (1991-1993) were also examined. RESULTS: The candidate antigens were aldolase A (ALDOA) and fumarate hydratase (FH). In AlphaLISA, patients with TIA or aCI had higher anti-ALDOA antibody (ALDOA-Ab) and anti-FH antibody (FH-Ab) levels than the HDs (P < 0.05). In a multivariate logistic regression analysis, the ALDOA-Ab (odds ratio [OR]: 2.46, P = 0.0050) and FH-Ab (OR: 2.49, P = 0.0037) levels were independent predictors of TIA. According to the case-control study, the ALDOA-Ab (OR: 2.50, P < 0.01) and FH-Ab (OR: 2.60, P < 0.01) levels were associated with aCI risk. In a correlation analysis, both ALDOA-Abs and FH-Abs were well associated with hypertension, coronary heart disease, and habitual smoking. These antibody levels also correlated well with maximum intima-media thickness, which reflects atherosclerotic stenosis. CONCLUSIONS: ALDOA-Abs and FH-Abs can be novel potential biomarkers for predicting atherosclerotic TIA and aCI.


Assuntos
Autoanticorpos/sangue , Infarto Cerebral , Ataque Isquêmico Transitório , Biomarcadores/sangue , Estudos de Casos e Controles , Infarto Cerebral/sangue , Infarto Cerebral/epidemiologia , Frutose-Bifosfato Aldolase/imunologia , Humanos , Ataque Isquêmico Transitório/sangue , Ataque Isquêmico Transitório/epidemiologia
15.
BMC Neurol ; 21(1): 277, 2021 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-34253185

RESUMO

BACKGROUND: Myasthenia gravis (MG) can occur as a paraneoplastic phenomenon associated with thymoma. The association of MG with renal cell carcinoma (RCC) is not clear. Herein, we describe six cases of MG associated with RCC. METHODS: There were 283 patients diagnosed with MG admitted to our hospital from 2014 to 2019. Among them, 6 patients also had RCC. None of them had immune checkpoint inhibitor therapies. We performed a retrospective clinical data collection and follow-up studies of these 6 patients. RESULTS: These 6 patients with an average MG onset age of 61.3 ± 13.3 years, were all positive for anti-acetylcholine receptor antibodies. MG symptoms appeared after RCC resection in 3 cases. RCC was discovered after the onset of MG in 2 cases, and synchronously with MG in 1 case. After nephrectomy, the MG symptoms showed a stable complete remission in 1 case. Among them, four patients met the diagnostic criteria of possible paraneoplastic neurological syndromes. CONCLUSIONS: Except for thymoma, patients with MG should pay attention to other tumors including RCC. MG may be a paraneoplastic syndrome of RCC, and further studies are needed to elucidate the relationship.


Assuntos
Carcinoma de Células Renais/diagnóstico , Neoplasias Renais/diagnóstico , Miastenia Gravis/diagnóstico , Síndromes Paraneoplásicas/diagnóstico , Adulto , Idoso , Autoanticorpos/sangue , Carcinoma de Células Renais/sangue , Carcinoma de Células Renais/complicações , Feminino , Seguimentos , Humanos , Neoplasias Renais/sangue , Neoplasias Renais/complicações , Masculino , Pessoa de Meia-Idade , Miastenia Gravis/sangue , Miastenia Gravis/complicações , Síndromes Paraneoplásicas/sangue , Síndromes Paraneoplásicas/complicações , Estudos Retrospectivos
16.
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
17.
Adv Clin Chem ; 103: 1-45, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34229848

RESUMO

Lung cancer (LC) accounts for the majority of cancer-related deaths worldwide. Although screening the high-risk population by low-dose CT (LDCT) has reduced mortality, the cost and high false positivity rate has prevented its general diagnostic use. As such, better and more specific minimally invasive biomarkers are needed in general and for early LC detection, specifically. Autoantibodies produced by humoral immune response to tumor-associated antigens (TAA) are emerging as a promising noninvasive biomarker for LC. Given the low sensitivity of any one single autoantibody, a panel approach could provide a more robust and promising strategy to detect early stage LC. In this review, we summarize the background of TAA autoantibodies (TAAb) and the techniques currently used for identifying TAA, as well as recent findings of LC specific antigens and TAAb. This review provides guidance toward the development of accurate and reliable TAAb as immunodiagnostic biomarkers in the early detection of LC.


Assuntos
Anticorpos Antineoplásicos/sangue , Antígenos de Neoplasias/imunologia , Autoanticorpos/sangue , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/imunologia , Humanos , Proteínas de Neoplasias/sangue , Proteínas de Neoplasias/metabolismo
18.
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
19.
Front Immunol ; 12: 628564, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34211456

RESUMO

Neutrophil extracellular traps (NETs) and mitochondrial DNA (mtDNA) are inflammatory mediators involved in the development of type 1 diabetes (T1D). Pancreas-infiltrating neutrophils can release NETs, contributing to the inflammatory process. Levels of NETs are increased in serum from patients with T1D and mtDNA is increased in adult T1D patients. Our aim was to investigate extracellular DNA (NETs, mtDNA and nuclear DNA) in children with newly diagnosed T1D and in children at high risk of the disease. We also elucidated if extracellular DNA short after diagnosis could predict loss of endogenous insulin production. Samples were analysed for mtDNA and nuclear DNA using droplet digital PCR and NETs were assessed by a NET-remnants ELISA. In addition, in vitro assays for induction and degradation of NETs, as well as analyses of neutrophil elastase, HLA genotypes, levels of c-peptide, IL-1beta, IFN and autoantibodies (GADA, IA-2A, IAA and ZnT8A) were performed. In serum from children 10 days after T1D onset there was an increase in NETs (p=0.007), mtDNA (p<0.001) and nuclear DNA (p<0.001) compared to healthy children. The elevated levels were found only in younger children. In addition, mtDNA increased in consecutive samples short after onset (p=0.017). However, levels of extracellular DNA short after onset did not reflect future loss of endogenous insulin production. T1D serum induced NETs in vitro and did not deviate in the ability to degrade NETs. HLA genotypes and autoantibodies, except for ZnT8A, were not associated with extracellular DNA in T1D children. Serum from children with high risk of T1D showed fluctuating levels of extracellular DNA, sometimes increased compared to healthy children. Therefore, extracellular DNA in serum from autoantibody positive high-risk children does not seem to be a suitable biomarker candidate for prediction of T1D. In conclusion, we found increased levels of extracellular DNA in children with newly diagnosed T1D, which might be explained by an ongoing systemic inflammation.


Assuntos
Núcleo Celular/genética , DNA Mitocondrial/sangue , DNA/sangue , Diabetes Mellitus Tipo 1/sangue , Armadilhas Extracelulares/metabolismo , Adolescente , Fatores Etários , Autoanticorpos/sangue , Biomarcadores/sangue , Estudos de Casos e Controles , Criança , Diabetes Mellitus Tipo 1/genética , Diabetes Mellitus Tipo 1/imunologia , Feminino , Humanos , Estudos Longitudinais , Masculino , Medição de Risco , Fatores de Risco , Regulação para Cima
20.
Int J Lab Hematol ; 43 Suppl 1: 103-108, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34288437

RESUMO

TTP is a life-threatening disorder diagnosed using a combination of clinical information and laboratory results. ADAMTS13 activity and antibody testing represent a major advance in the field, but results can sometimes be difficult to interpret due to technical aspects of the tests and characteristics of the causative antibodies in acquired TTP. Genetic testing for ADAMTS13 mutations is also now available to assist with the diagnosis of inherited TTP. This review will focus on ADAMTS13 testing and will highlight patient and laboratory aspects that can lead to diagnostic difficulty. The effects of TTP therapies on test results will also be discussed.


Assuntos
Proteína ADAMTS13/sangue , Testes de Coagulação Sanguínea , Púrpura Trombocitopênica Trombótica/sangue , Púrpura Trombocitopênica Trombótica/diagnóstico , Autoanticorpos/sangue , Autoanticorpos/imunologia , Coagulação Sanguínea , Testes de Coagulação Sanguínea/métodos , Testes de Coagulação Sanguínea/tendências , Terapia Combinada/efeitos adversos , Terapia Combinada/métodos , Gerenciamento Clínico , Suscetibilidade a Doenças , Humanos , Mutação , Púrpura Trombocitopênica Trombótica/etiologia , Púrpura Trombocitopênica Trombótica/terapia , Resultado do Tratamento
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