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1.
Medicina (Kaunas) ; 56(10)2020 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-33028028

RESUMO

The clinical spectrum of novel coronavirus infection appears to be wide, encompassing asymptomatic infection, mild upper respiratory tract illness, and severe viral pneumonia, with respiratory failure and even death. Autoantibodies, especially antiphospholipid antibodies, can occur in severe infections. Other autoantibodies are seldom reported. Here, a 60-year-old female patient without dry-mouth symptoms detected positive for anti-60 kDa SSA/Ro antibodies on day 43 after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. To investigate this unique clinical case of SARS-CoV-2 infection, immunological characteristics of this case were detected by using flow cytometry and were compared to the other three groups of patients-health subjects, 2019 novel coronavirus disease (COVID-19) recovery patients, and Sjögren's syndrome (SS) patients. Monitoring the autoantibody level and the development of subsequently related autoimmune diseases are warranted after SARS-CoV-2 infection.


Assuntos
Anticorpos Antinucleares/imunologia , Anticorpos Antivirais/imunologia , Betacoronavirus/imunologia , Infecções por Coronavirus/imunologia , Imunofenotipagem , Pneumonia Viral/imunologia , Feminino , Citometria de Fluxo , Humanos , Pessoa de Meia-Idade , Pandemias , Síndrome de Sjogren
2.
Clin Rheumatol ; 39(11): 3171-3175, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32844364

RESUMO

We treated two patients with severe respiratory failure due to coronavirus disease 2019 (COVID-19). Case 1 was a 73-year-old woman, and Case 2 was a 65-year-old-man. Neither of them had a history of autoimmune disease. Chest computed tomography scans before the antiviral therapy showed bilateral multiple patchy ground-glass opacities (GGO) consistent with COVID-19 pneumonia. The GGO regressed over the course of the antiviral treatment; however, new non-segmental patchy consolidations emerged, which resembled those of interstitial lung disease (ILD), specifically collagen vascular disease-associated ILD. We tested the patients' sera for autoantibodies and discovered that both patients had high anti-SSA/Ro antibody titers. In Case 1, the patient recovered with antiviral therapy alone. However, in Case 2, the patient did not improve with antiviral therapy alone but responded well to corticosteroid therapy (methylprednisolone) and made a full recovery. The relationship between some immunological responses and COVID-19 pneumonia exacerbation has been discussed previously; our discovery of the elevation of anti-SSA/Ro antibodies suggests a contribution from autoimmunity functions of the immune system. Although it is unclear whether the elevation of anti-SSA/Ro antibodies was a cause or an outcome of aggravated COVID-19 pneumonia, we hypothesize that both patients developed aggravated the COVID-19 pneumonia due to an autoimmune response. In COVID-19 lung injury, there may be a presence of autoimmunity factors in addition to the known effects of cytokine storms. In patients with COVID-19, a high level of anti-SSA/Ro52 antibodies may be a surrogate marker of pneumonia severity and poor prognosis.


Assuntos
Anticorpos Antinucleares/imunologia , Infecções por Coronavirus/imunologia , Doenças Pulmonares Intersticiais/imunologia , Pneumonia Viral/imunologia , Insuficiência Respiratória/imunologia , Idoso , Amidas/uso terapêutico , Antivirais/uso terapêutico , Betacoronavirus , Infecções por Coronavirus/complicações , Infecções por Coronavirus/diagnóstico por imagem , Infecções por Coronavirus/tratamento farmacológico , Feminino , Glucocorticoides/uso terapêutico , Guanidinas/uso terapêutico , Humanos , Hidroxicloroquina/uso terapêutico , Doenças Pulmonares Intersticiais/diagnóstico por imagem , Doenças Pulmonares Intersticiais/tratamento farmacológico , Doenças Pulmonares Intersticiais/etiologia , Masculino , Metilprednisolona/uso terapêutico , Pandemias , Pneumonia Viral/complicações , Pneumonia Viral/diagnóstico por imagem , Pneumonia Viral/tratamento farmacológico , Pregnenodionas/uso terapêutico , Pirazinas/uso terapêutico , Recuperação de Função Fisiológica , Síndrome do Desconforto Respiratório do Adulto/etiologia , Síndrome do Desconforto Respiratório do Adulto/imunologia , Insuficiência Respiratória/etiologia , Índice de Gravidade de Doença , Tomografia Computadorizada por Raios X
3.
Clin Rheumatol ; 39(9): 2811-2815, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32720260

RESUMO

In the midst of the COVID-19 pandemic, further understanding of its complications points towards dysregulated immune response as a major component. Systemic lupus erythematosus (SLE) is also a disease of immune dysregulation leading to multisystem compromise. We present a case of new-onset SLE concomitantly with COVID-19 and development of antiphospholipid antibodies. An 18-year-old female that presented with hemodynamic collapse and respiratory failure, progressed to cardiac arrest, and had a pericardial tamponade drained. She then progressed to severe acute respiratory distress syndrome, severe ventricular dysfunction, and worsening renal function with proteinuria and hematuria. Further studies showed bilateral pleural effusions, positive antinuclear and antidouble-stranded DNA antibodies, lupus anticoagulant, and anticardiolipin B. C3 and C4 levels were low. SARS-Cov-2 PCR was positive after 2 negative tests. She also developed multiple deep venous thrombosis, in the setting of positive antiphospholipid antibodies and lupus anticoagulant. In terms of pathophysiology, COVID-19 is believed to cause a dysregulated cytokine response which could potentially be exacerbated by the shift in Th1 to Th2 response seen in SLE. Also, it is well documented that viral infections are an environmental factor that contributes to the development of autoimmunity; however, COVID-19 is a new entity, and it is not known if it could trigger autoimmune conditions. Additionally, it is possible that SARS-CoV-2, as it happens with other viruses, might lead to the formation of antiphospholipid antibodies, potentially contributing to the increased rates of thrombosis seen in COVID-19.


Assuntos
Síndrome Antifosfolipídica/imunologia , Infecções por Coronavirus/imunologia , Lúpus Eritematoso Sistêmico/imunologia , Pneumonia Viral/imunologia , Adolescente , Anemia/etiologia , Anticorpos Anticardiolipina/imunologia , Anticorpos Antinucleares/imunologia , Anticorpos Monoclonais Humanizados/uso terapêutico , Síndrome Antifosfolipídica/complicações , Síndrome Antifosfolipídica/diagnóstico , Síndrome Antifosfolipídica/terapia , Anuria/etiologia , Betacoronavirus , Tamponamento Cardíaco/diagnóstico por imagem , Tamponamento Cardíaco/etiologia , Tamponamento Cardíaco/terapia , Complemento C3/imunologia , Complemento C4/imunologia , Infecções por Coronavirus/complicações , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/terapia , DNA/imunologia , Ecocardiografia , Evolução Fatal , Feminino , Parada Cardíaca/etiologia , Hematúria/etiologia , Humanos , Inibidor de Coagulação do Lúpus/imunologia , Lúpus Eritematoso Sistêmico/sangue , Lúpus Eritematoso Sistêmico/complicações , Lúpus Eritematoso Sistêmico/diagnóstico , Pandemias , Posicionamento do Paciente , Pericardiocentese , Pneumonia Viral/complicações , Pneumonia Viral/diagnóstico , Pneumonia Viral/terapia , Decúbito Ventral , Proteinúria/etiologia , Diálise Renal , Insuficiência Renal/etiologia , Insuficiência Renal/terapia , Respiração Artificial , Síndrome do Desconforto Respiratório do Adulto/etiologia , Síndrome do Desconforto Respiratório do Adulto/terapia , Insuficiência Respiratória/etiologia , Insuficiência Respiratória/terapia , Trombocitopenia/etiologia , Trombose Venosa/etiologia , Disfunção Ventricular Esquerda/diagnóstico por imagem , Disfunção Ventricular Esquerda/etiologia
4.
Rheumatol Int ; 40(10): 1539-1554, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32666137

RESUMO

The coronavirus disease-2019 (COVID-19) pandemic is likely to pose new challenges to the rheumatology community in the near and distant future. Some of the challenges, like the severity of COVID-19 among patients on immunosuppressive agents, are predictable and are being evaluated with great care and effort across the globe. A few others, such as atypical manifestations of COVID-19 mimicking rheumatic musculoskeletal diseases (RMDs) are being reported. Like in many other viral infections, severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection can potentially lead to an array of rheumatological and autoimmune manifestations by molecular mimicry (cross-reacting epitope between the virus and the host), bystander killing (virus-specific CD8 + T cells migrating to the target tissues and exerting cytotoxicity), epitope spreading, viral persistence (polyclonal activation due to the constant presence of viral antigens driving immune-mediated injury) and formation of neutrophil extracellular traps. In addition, the myriad of antiviral drugs presently being tried in the treatment of COVID-19 can result in several rheumatic musculoskeletal adverse effects. In this review, we have addressed the possible spectrum and mechanisms of various autoimmune and rheumatic musculoskeletal manifestations that can be precipitated by COVID-19 infection, its therapy, and the preventive strategies to contain the infection.


Assuntos
Doenças Autoimunes/fisiopatologia , Infecções por Coronavirus/fisiopatologia , Doenças Musculoesqueléticas/fisiopatologia , Pneumonia Viral/fisiopatologia , Doenças Reumáticas/fisiopatologia , Anticorpos Antinucleares/imunologia , Anticorpos Antifosfolipídeos/imunologia , Antivirais/efeitos adversos , Artralgia/etiologia , Artralgia/imunologia , Artralgia/fisiopatologia , Doenças Autoimunes/etiologia , Doenças Autoimunes/imunologia , Betacoronavirus , Transtornos da Coagulação Sanguínea/etiologia , Transtornos da Coagulação Sanguínea/imunologia , Transtornos da Coagulação Sanguínea/fisiopatologia , Infecções por Coronavirus/complicações , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/imunologia , Reações Cruzadas/imunologia , Armadilhas Extracelulares/imunologia , Produtos de Degradação da Fibrina e do Fibrinogênio , Síndrome de Guillain-Barré/etiologia , Síndrome de Guillain-Barré/imunologia , Síndrome de Guillain-Barré/fisiopatologia , Humanos , Inibidor de Coagulação do Lúpus/imunologia , Mimetismo Molecular , Síndrome de Linfonodos Mucocutâneos/etiologia , Síndrome de Linfonodos Mucocutâneos/imunologia , Síndrome de Linfonodos Mucocutâneos/fisiopatologia , Debilidade Muscular/etiologia , Debilidade Muscular/imunologia , Debilidade Muscular/fisiopatologia , Doenças Musculoesqueléticas/etiologia , Doenças Musculoesqueléticas/imunologia , Mialgia/etiologia , Mialgia/imunologia , Mialgia/fisiopatologia , Miocardite/etiologia , Miocardite/imunologia , Miocardite/fisiopatologia , Pandemias , Pneumonia Viral/complicações , Pneumonia Viral/tratamento farmacológico , Pneumonia Viral/imunologia , Doenças Reumáticas/etiologia , Doenças Reumáticas/imunologia
5.
PLoS Pathog ; 16(7): e1008591, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32645118

RESUMO

Reactive arthritis, an autoimmune disorder, occurs following gastrointestinal infection with invasive enteric pathogens, such as Salmonella enterica. Curli, an extracellular, bacterial amyloid with cross beta-sheet structure can trigger inflammatory responses by stimulating pattern recognition receptors. Here we show that S. Typhimurium produces curli amyloids in the cecum and colon of mice after natural oral infection, in both acute and chronic infection models. Production of curli was associated with an increase in anti-dsDNA autoantibodies and joint inflammation in infected mice. The negative impacts on the host appeared to be dependent on invasive systemic exposure of curli to immune cells. We hypothesize that in vivo synthesis of curli contributes to known complications of enteric infections and suggest that cross-seeding interactions can occur between pathogen-produced amyloids and amyloidogenic proteins of the host.


Assuntos
Artrite Infecciosa/imunologia , Proteínas de Bactérias/imunologia , Febre Tifoide/imunologia , Animais , Anticorpos Antinucleares/imunologia , Artrite Experimental/imunologia , Artrite Experimental/metabolismo , Artrite Infecciosa/metabolismo , Proteínas de Bactérias/biossíntese , Intestino Grosso/imunologia , Intestino Grosso/microbiologia , Camundongos , Febre Tifoide/metabolismo
6.
J Investig Med High Impact Case Rep ; 8: 2324709620933438, 2020.
Artigo em Inglês | MEDLINE | ID: covidwho-535847

RESUMO

In this article, we present a case of a young female patient with previously diagnosed lupus pneumonitis, now with a flare and new superimposed COVID-19 infection that was treated with intravenous steroids. On computed tomography scans, she had extensive interstitial lung fibrosis in addition to a positive COVID-19 polymerase chain reaction test requiring 6 L of oxygen via nasal cannula on admission. After administration of methylprednisolone, the patient improved and was weaned off her oxygen requirements and was discharged home.


Assuntos
Infecções por Coronavirus/complicações , Lúpus Eritematoso Sistêmico/complicações , Pneumonia Viral/complicações , Pneumonia/complicações , Anticorpos Antinucleares/imunologia , Antirreumáticos/uso terapêutico , Betacoronavirus , Tamponamento Cardíaco , Complemento C3/imunologia , Complemento C4/imunologia , Infecções por Coronavirus/diagnóstico por imagem , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/terapia , DNA , Progressão da Doença , Inibidores Enzimáticos/uso terapêutico , Feminino , Produtos de Degradação da Fibrina e do Fibrinogênio , Glucocorticoides/uso terapêutico , Humanos , Hidroxicloroquina/uso terapêutico , Pulmão/diagnóstico por imagem , Lúpus Eritematoso Sistêmico/diagnóstico por imagem , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Lúpus Eritematoso Sistêmico/imunologia , Nefrite Lúpica , Linfopenia/etiologia , Metilprednisolona/uso terapêutico , Ácido Micofenólico/uso terapêutico , Oxigenoterapia , Pandemias , Pneumonia/diagnóstico por imagem , Pneumonia/imunologia , Pneumonia/terapia , Pneumonia Viral/diagnóstico por imagem , Pneumonia Viral/terapia , Tomografia Computadorizada por Raios X , Adulto Jovem
7.
J Investig Med High Impact Case Rep ; 8: 2324709620933438, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32500773

RESUMO

In this article, we present a case of a young female patient with previously diagnosed lupus pneumonitis, now with a flare and new superimposed COVID-19 infection that was treated with intravenous steroids. On computed tomography scans, she had extensive interstitial lung fibrosis in addition to a positive COVID-19 polymerase chain reaction test requiring 6 L of oxygen via nasal cannula on admission. After administration of methylprednisolone, the patient improved and was weaned off her oxygen requirements and was discharged home.


Assuntos
Infecções por Coronavirus/complicações , Lúpus Eritematoso Sistêmico/complicações , Pneumonia Viral/complicações , Pneumonia/complicações , Anticorpos Antinucleares/imunologia , Antirreumáticos/uso terapêutico , Betacoronavirus , Tamponamento Cardíaco , Complemento C3/imunologia , Complemento C4/imunologia , Infecções por Coronavirus/diagnóstico por imagem , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/terapia , DNA , Progressão da Doença , Inibidores Enzimáticos/uso terapêutico , Feminino , Produtos de Degradação da Fibrina e do Fibrinogênio , Glucocorticoides/uso terapêutico , Humanos , Hidroxicloroquina/uso terapêutico , Pulmão/diagnóstico por imagem , Lúpus Eritematoso Sistêmico/diagnóstico por imagem , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Lúpus Eritematoso Sistêmico/imunologia , Nefrite Lúpica , Linfopenia/etiologia , Metilprednisolona/uso terapêutico , Ácido Micofenólico/uso terapêutico , Oxigenoterapia , Pandemias , Pneumonia/diagnóstico por imagem , Pneumonia/imunologia , Pneumonia/terapia , Pneumonia Viral/diagnóstico por imagem , Pneumonia Viral/terapia , Tomografia Computadorizada por Raios X , Adulto Jovem
8.
Medicine (Baltimore) ; 99(20): e20192, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32443340

RESUMO

The aims of this study were to compare diagnostic value of anti-ribosomal P protein antibody (anti-P), anti-Smith antibody (anti-Sm), anti-double-stranded DNA antibody (anti-dsDNA), anti-nucleosome antibody (ANuA), and anti-histone antibody (AHA) for systemic lupus erythematosus (SLE) as well as explore the correlation between anti-P and SLE.A retrospective study was performed with 487 SLE patients, 235 non-SLE rheumatic diseases, and 124 healthy subjects from January 2015 to December 2018. Clinical manifestations, laboratory results and Systemic Lupus Erythematosus Disease Activity Index (SLEDAI)-2000 scores were analyzed between anti-P/+/ and anti-P/-/ patients. SPSS19.0 statistical software was used for data analysis.The sensitivities of anti-P, anti-Sm, anti-dsDNA, ANuA, and AHA in SLE were 31.6%, 20.7%, 45.0%, 27.9%, and 14.6%, and the specificities were 99.2%, 99.4%, 98.9%, 98.3%, and 96.7%, respectively. Only 27.9% of SLE had a single positive anti-P while the other 4 antibodies were all negative. There were significant differences in the age of onset, skin erythema, urinary protein, creatinine and serum IgG, IgM, C3, C4 between anti-P/+/ and anti-P/-/ patients (P < .05). When anti-Sjogren syndrome A antibody, anti-P were positive and anti-dsDNA was negative, the incidence of skin erythema was the highest (35.1%). Compared with anti-P/-/ patients, anti-P/+/ patients had higher SLEDAI scores (P < .001).Anti-P, anti-Sm, anti-dsDNA, ANuA, and AHA have high specificity but poor sensitivity in the diagnosis of SLE; combined detection can greatly improve the detection rate. Anti-P is more valuable in the diagnosis of SLE when other specific autoantibodies are negative. SLE patients with positive anti-P have an earlier onset age and are more prone to skin erythema, lupus nephritis as well as higher disease activity.


Assuntos
Autoanticorpos/sangue , Lúpus Eritematoso Sistêmico/imunologia , Proteínas de Membrana Transportadoras/imunologia , Proteínas Ribossômicas/imunologia , Adulto , Anticorpos Antinucleares/imunologia , DNA/antagonistas & inibidores , DNA/metabolismo , Eritema/imunologia , Eritema/patologia , Feminino , Histonas/antagonistas & inibidores , Histonas/metabolismo , Humanos , Lúpus Eritematoso Sistêmico/diagnóstico , Lúpus Eritematoso Sistêmico/patologia , Nefrite Lúpica/imunologia , Masculino , Pessoa de Meia-Idade , Nucleossomos/metabolismo , Estudos Retrospectivos , Doenças Reumáticas/imunologia , Sensibilidade e Especificidade , Dermatopatias/epidemiologia
9.
Int Heart J ; 61(2): 413-418, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32224603

RESUMO

Anticentriole autoantibodies-positive systemic sclerosis (SSc) has been reported to develop pulmonary arterial hypertension (PAH) at a high rate. In this report, we describe two patients with anticentriole antibodies-positive SSc-PAH who were treated with pulmonary vasodilators. Both cases were elderly women with poor physical conditions and clinical findings of SSc. Case 1 was resistant to combination therapy with pulmonary vasodilators; in Case 2, hemodynamic improvement was obtained by upfront combination therapy at an early stage. Because anticentriole antibodies-positive SSc-PAH rapidly deteriorates, careful hemodynamic observation and timely aggressive use of pulmonary vasodilators should be considered.


Assuntos
Anticorpos Antinucleares/imunologia , Centríolos/imunologia , Antagonistas dos Receptores de Endotelina/uso terapêutico , Hipertensão Arterial Pulmonar/tratamento farmacológico , Escleroderma Sistêmico/imunologia , Vasodilatadores/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Autoanticorpos/imunologia , Bosentana/uso terapêutico , Cateterismo Cardíaco , Quimioterapia Combinada , Epoprostenol/análogos & derivados , Epoprostenol/uso terapêutico , Feminino , Volume Expiratório Forçado , Humanos , Mesilato de Imatinib/uso terapêutico , Inibidores de Proteínas Quinases/uso terapêutico , Hipertensão Arterial Pulmonar/diagnóstico por imagem , Hipertensão Arterial Pulmonar/etiologia , Hipertensão Arterial Pulmonar/fisiopatologia , Capacidade de Difusão Pulmonar , Pirimidinas/uso terapêutico , Escleroderma Sistêmico/complicações , Escleroderma Sistêmico/tratamento farmacológico , Citrato de Sildenafila/uso terapêutico , Sulfonamidas/uso terapêutico , Tadalafila/uso terapêutico , Tomografia Computadorizada por Raios X
10.
Proc Natl Acad Sci U S A ; 117(16): 9054-9063, 2020 04 21.
Artigo em Inglês | MEDLINE | ID: mdl-32295878

RESUMO

Invariant natural killer T (iNKT) cells serve as early rapid responders in the innate immune response to self-derived autoantigens and pathogen-derived danger signals and antigens. iNKT cells can serve both as helpers for effector B cells and negatively regulate autoreactive B cells. Specifically, iNKT cells drive B cell proliferation, class switch, and antibody production to induce primary antigen-specific immune responses. On the other hand, inflammasome-mediated activation drives accumulation of neutrophils, which license iNKT cells to negatively regulate autoreactive B cells via Fas ligand (FasL). This positions iNKT cells at an apex to support or inhibit B cell responses in inflammation. However, it is unknown which effector mechanism dominates in the face of cognate glycolipid activation during chronic inflammation, as might result from glycolipid vaccination or infection during chronic autoimmune disease. We stimulated iNKT cells by cognate glycolipid antigen α-galactosylceramide (αGalCer) and measured B cell activation during interleukin 18 (IL-18)-induced chronic inflammation. Moreover, glycolipid-activated iNKT cells increased the serum concentration of autoantibodies, frequency of germinal center (GC) B cells, and antigen-specific plasma cells induced during chronic IL-18-mediated inflammation, as compared with IL-18 alone. Further, activation of iNKT cells via cognate glycolipid during IL-18-mediated inflammation overrides the licensing function of neutrophils, instead inducing iNKT follicular helper (iNKTfh) cells that in turn promote autoimmunity. Thus, our data demonstrate that glycolipids which engage iNKT cells support antigen-specific B cell help during inflammasome-mediated inflammation.


Assuntos
Anticorpos Antinucleares/imunologia , Autoimunidade , Galactosilceramidas/imunologia , Inflamação/imunologia , Células T Matadoras Naturais/imunologia , Animais , Anticorpos Antinucleares/sangue , Linfócitos B/imunologia , Doença Crônica , Modelos Animais de Doenças , Feminino , Humanos , Inflamação/sangue , Injeções Intraperitoneais , Interleucina-18/administração & dosagem , Interleucina-18/imunologia , Masculino , Camundongos , Camundongos Transgênicos , Proteínas Recombinantes/administração & dosagem , Proteínas Recombinantes/imunologia
12.
J Neuroimmunol ; 341: 577184, 2020 04 15.
Artigo em Inglês | MEDLINE | ID: mdl-32058173

RESUMO

We present an illustrative case of a 62-year-old woman with small cell lung cancer who developed progressive worsening of pre-existing anti-Hu antibody associated sensory neuronopathy after treatment with programmed cell death-1 (PD-1) inhibitor, nivolumab. We review the literature and identify 6 reported cases to understand the clinical outcomes of patients with anti-Hu paraneoplastic neurologic syndrome (PNS) treated with anti-PD-1 treatment. The PNS clinical spectrum comprised of encephalitis, a combination of sensory neuronopathy and anti-NMDAR encephalitis, isolated sensory neuronopathy, and encephalomyelitis. Immune checkpoint inhibitor have the potential to worsen pre-existing anti-Hu PNS and may promote the development of anti-Hu PNS.


Assuntos
Anticorpos Antinucleares/sangue , Antineoplásicos Imunológicos/efeitos adversos , Autoantígenos/imunologia , Proteínas ELAV/imunologia , Nivolumabe/efeitos adversos , Síndromes Paraneoplásicas do Sistema Nervoso/etiologia , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Anticorpos Antinucleares/imunologia , Antineoplásicos Imunológicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carboplatina/administração & dosagem , Carcinoma de Células Pequenas/complicações , Carcinoma de Células Pequenas/tratamento farmacológico , Carcinoma de Células Pequenas/imunologia , Carcinoma de Células Pequenas/secundário , Neoplasias Cerebelares/complicações , Neoplasias Cerebelares/tratamento farmacológico , Neoplasias Cerebelares/imunologia , Neoplasias Cerebelares/secundário , Terapia Combinada , Progressão da Doença , Etoposídeo/administração & dosagem , Feminino , Humanos , Neoplasias Pulmonares/complicações , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/imunologia , Neoplasias Pulmonares/radioterapia , Pessoa de Meia-Idade , Nivolumabe/uso terapêutico , Síndromes Paraneoplásicas do Sistema Nervoso/induzido quimicamente , Síndromes Paraneoplásicas do Sistema Nervoso/imunologia , Radioterapia Adjuvante , Resultado do Tratamento
13.
Scand J Rheumatol ; 49(3): 233-238, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32043398

RESUMO

Objective: There has been no previous study comparing the frequency of sicca symptoms and Sjögren's syndrome (SS) in coeliac patients (CPs) and healthy controls (HCs) using a tight screening method. The aim of this study was to compare the frequency of sicca symptoms and SS in HCs and CPs.Method: The study included 80 CPs and 100 HCs. This study was designed as a case-control study with four phases. The frequency of SS in CPs and HCs was defined according to the 2002 American-European Consensus Group (AECG) and 2012 American College of Rheumatology (ACR) classification criteria. The frequency of sicca symptoms and SS was compared between CPs and HCs.Results: Ocular and oral symptoms occurred in 22% and 26% of CPs, respectively, compared to 13% and 10% of HCs, respectively. Proportions with oral symptoms were statistically significantly different between CPs and HCs (p = 0.005), whereas there was no significant difference for ocular symptoms (p = 0.113). According to ACR and AECG criteria, the prevalence of SS was 3.8% and 5.0% in CPs and 3.0% and 2.0% in HCs, respectively.Conclusion: Although oral symptoms were more frequent in CPs than in HCs, the frequency of SS was not different between the groups. The increased frequency of oral symptoms may be related to reasons other than autoimmunity.


Assuntos
Doença Celíaca/epidemiologia , Síndromes do Olho Seco/epidemiologia , Síndrome de Sjogren/epidemiologia , Xerostomia/epidemiologia , Adulto , Anticorpos Antinucleares/imunologia , Estudos de Casos e Controles , Doença Celíaca/imunologia , Síndromes do Olho Seco/imunologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Fator Reumatoide/imunologia , Síndrome de Sjogren/imunologia , Xerostomia/imunologia
16.
Clin Immunol ; 212: 108349, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31982644

RESUMO

Systemic lupus erythematosus (SLE) is a prototypic autoimmune disease characterized by immune complexes. Because these complexes contain mitochondrial components, we assessed the presence of antibodies to whole mitochondria (wMITO) using an ELISA in which mitochondria from mouse liver are bound to microtiter plates pre-coated with poly-l-lysine. Studies with this ELISA demonstrated that SLE plasmas contain abundant anti-wMITO activity. While digestion with DNase 1 did not affect anti-wMITO activity, adsorption of plasma on DNA affinity columns could reduce binding activity. Assay for anti-mitochondrial antibodies (AMA) by immunofluorescence and an ELISA with the M2 antigen (2-oxo-acid dehydrogenase protein complex) showed a low frequency of positivity, indicating that AMA and anti-wMITO are distinct specificities. In the study of 204 patients with SLE, the levels of anti-wMITO were higher in active SLE and correlated with levels of anti-DNA. These findings suggest that anti-wMITO can form immune complexes with mitochondria which may drive pathogenesis.


Assuntos
Anticorpos Antinucleares/imunologia , Autoanticorpos/imunologia , Lúpus Eritematoso Sistêmico/imunologia , Mitocôndrias/imunologia , Animais , Complexo Antígeno-Anticorpo , Autoantígenos/imunologia , Estudos de Casos e Controles , DNA/imunologia , Desoxirribonuclease I , Ensaio de Imunoadsorção Enzimática , Humanos , Cirrose Hepática Biliar/imunologia , Espectrometria de Massas , Camundongos , Mitocôndrias Hepáticas/imunologia , Proteínas Mitocondriais/imunologia , Polilisina , Proteômica
17.
Arthritis Rheumatol ; 72(6): 997-1002, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-31943822

RESUMO

OBJECTIVE: To address whether a targeted modulation of the abnormal expression of Hsp70 and autoantibodies against this molecule in systemic lupus erythematosus can influence disease. METHODS: Lupus-prone (NZB × NZW)F1 mice that had been DNA-vaccinated with plasmids encoding Hsp70 and controls were monitored for lupus disease parameters including anti-double stranded DNA (anti-dsDNA) autoantibodies and cytokines using enzyme-linked immunosorbent assay, and for kidney function and pathology. The phenotypic and numerical changes in relevant immune cells were evaluated by flow cytometry, and cell function was assessed. RESULTS: Mice that had been DNA-vaccinated with Hsp70 displayed marked suppression of anti-dsDNA antibody production, reduced renal disease, and antiinflammatory responses that are associated with a significantly extended survival, compared to controls. These protective effects in Hsp70-vaccinated mice were associated with an induction of tolerogenic immune responses and an expansion of functional Treg cells. CONCLUSION: DNA vaccination with Hsp70 suppresses murine lupus by inducing tolerogenic immune responses and antiinflammatory immune responses associated with reduced disease manifestations and increased mouse survival.


Assuntos
Anticorpos Antinucleares/efeitos dos fármacos , Autoanticorpos/efeitos dos fármacos , Proteínas de Choque Térmico HSP70/farmacologia , Lúpus Eritematoso Sistêmico/prevenção & controle , Vacinas de DNA/farmacologia , Animais , Anticorpos Antinucleares/imunologia , Autoanticorpos/imunologia , DNA/imunologia , Modelos Animais de Doenças , Ensaio de Imunoadsorção Enzimática , Lúpus Eritematoso Sistêmico/imunologia , Camundongos , Camundongos Endogâmicos NZB
18.
Scand J Immunol ; 91(3): e12849, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31899559

RESUMO

The aim of study was to detect antinuclear antibodies (ANA) using indirect immunofluorescence assay (IIFA), linear immunoassay (LIA), chemiluminescence microparticle immunoassay (CMIA), multiple microbead immunoassay (MBI) and to compare these four methods in the performance of diagnosing systemic lupus erythematosus (SLE). Serum ANA were detected in 147 SLE cases and 42 healthy controls (HCs). The sensitivity, specificity, accuracy, positive predictive value and agreement, the area under the curve of four methods in diagnosing were calculated. Finally, a diagnostic model through logistic regression was constructed. The sensitivity of CMIA and IIFA in diagnosing SLE was 89.08% and 89.12%, higher than other two methods (P < .01), while highest specificity lied in CMIA (95.24%) and LIA (95.24%). The accuracy was highest in CMIA (91.01%), and lowest in LIA (83.07%). CMIA and the other three methods had good agreement, especially with LIA (κ = .798, 95% CI, 0.708-0.88). ANA-IIFA (OR = 1.016, P < .001) and anti-SSA antibodies (OR = 1.017, P = .043) were finally included in the SLE diagnostic model, with AUC value of 0.964 (95% CI, 0.936-0.991). SLE patients exhibited 14 various ANA patterns, especially AC-1, AC-4, and AC-5. Antibodies against SSA and dsDNA were mostly seen with AC-1 and AC-4 patterns, while antibodies against RNP, Sm, SSA, dsDNA, nucleosome and PO were most frequently observed with AC-5 pattern in SLE. CMIA method is a reliable screening test for detections of antibodies related to SLE. Using ANA-IIFA and anti-SSA antibodies by CMIA can discriminate SLE patients from HCs effectively.


Assuntos
Autoanticorpos/imunologia , Imunoensaio , Lúpus Eritematoso Sistêmico/diagnóstico , Lúpus Eritematoso Sistêmico/imunologia , Adulto , Idoso , Anticorpos Antinucleares/sangue , Anticorpos Antinucleares/imunologia , Área Sob a Curva , Autoanticorpos/sangue , Estudos de Casos e Controles , Feminino , Técnica Indireta de Fluorescência para Anticorpo , Humanos , Imunoensaio/métodos , Imunoensaio/normas , Medições Luminescentes/métodos , Medições Luminescentes/normas , Lúpus Eritematoso Sistêmico/sangue , Masculino , Pessoa de Meia-Idade , Razão de Chances , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Adulto Jovem
20.
Arthritis Rheumatol ; 72(1): 89-99, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31342656

RESUMO

OBJECTIVE: Long interspersed nuclear element 1 (LINE-1) encodes 2 proteins, the RNA binding protein p40 and endonuclease and reverse transcriptase (open-reading frame 2p [ORF2p]), which are both required for LINE-1 to retrotranspose. In cells expressing LINE-1, these proteins assemble with LINE-1 RNA and additional RNA binding proteins, some of which are well-known autoantigens in patients with systemic lupus erythematosus (SLE). This study was undertaken to investigate whether SLE patients also produce autoantibodies against LINE-1 p40. METHODS: Highly purified p40 protein was used to quantitate IgG autoantibodies in serum from 172 SLE patients and from disease controls and age-matched healthy subjects by immunoblotting and enzyme-linked immunosorbent assay (ELISA). Preparations of p40 that also contained associated proteins were analyzed by immunoblotting with patient sera. RESULTS: Antibodies reactive with p40 were detected in the majority of patients and many healthy controls. Their levels were higher in patients with SLE, but not those with systemic sclerosis, compared to healthy subjects (P = 0.01). Anti-p40 reactivity was higher in patients during a flare than in patients with disease in remission (P = 0.03); correlated with the SLE Disease Activity Index score (P = 0.0002), type I interferon score (P = 0.006), decrease in complement C3 level (P = 0.0001), the presence of anti-DNA antibodies (P < 0.0001) and anti-C1q antibodies (P = 0.004), and current or past history of nephritis (P = 0.02 and P = 0.003, respectively); and correlated inversely with age (r = -0.49, P < 0.0001). SLE patient sera also reacted with p40-associated proteins. CONCLUSION: Autoantibodies reacting with LINE-1 p40 characterize a population of SLE patients with severe and active disease. These autoantibodies may represent an early immune response against LINE-1 p40 that does not yet by itself imply clinically significant autoimmunity, but may represent an early, and still reversible, step toward SLE pathogenesis.


Assuntos
Autoanticorpos/imunologia , Proteínas de Ligação a DNA/imunologia , Lúpus Eritematoso Sistêmico/imunologia , Fatores Etários , Anticorpos Antinucleares/imunologia , Estudos de Casos e Controles , Complemento C1q/imunologia , Complemento C3/imunologia , Humanos , Elementos Nucleotídeos Longos e Dispersos/imunologia , Nefrite Lúpica/imunologia , Escleroderma Sistêmico/imunologia , Índice de Gravidade de Doença
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