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1.
Front Immunol ; 12: 724047, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34512651

RESUMO

Objectives: Impact of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic on individuals with arthritis has been highlighted whereas data on other rheumatic diseases, e.g., systemic lupus erythematosus (SLE), are scarce. Similarly to SLE, severe SARS-CoV-2 infection includes risks for thromboembolism, an unbalanced type I interferon response, and complement activation. Herein, SARS-CoV-2 antibodies in longitudinal samples collected prior to vaccination were analyzed and compared with SLE progression and antinuclear antibody (ANA) levels. Methods: One hundred patients (83 women) with established SLE and a regular visit to the rheumatologist (March 2020 to January 2021) were included. All subjects donated blood and had done likewise prior to the pandemic. SARS-CoV-2 antibody isotypes (IgG, IgA, IgM) to the cell receptor-binding S1-spike outer envelope protein were detected by ELISA, and their neutralizing capacity was investigated. IgG-ANA were measured by multiplex technology. Results: During the pandemic, 4% had PCR-confirmed infection but 36% showed SARS-CoV-2 antibodies of ≥1 isotype; IgA was the most common (30%), followed by IgM (9%) and IgG (8%). The antibodies had low neutralizing capacity and were detected also in prepandemic samples. Plasma albumin (p = 0.04) and anti-dsDNA (p = 0.003) levels were lower in patients with SARS-CoV-2 antibodies. Blood group, BMI, smoking habits, complement proteins, daily glucocorticoid dose, use of hydroxychloroquine, or self-reported coronavirus disease 2019 (COVID-19) symptoms (except fever, >38.5°C) did not associate with SARS-CoV-2 antibodies. Conclusion: Our data from early 2021 indicate that a large proportion of Swedish SLE patients had serological signs of exposure to SARS-CoV-2 but apparently with a minor impact on the SLE course. Use of steroids and hydroxychloroquine showed no distinct effects, and self-reported COVID-19-related symptoms correlated poorly with all antibody isotypes.


Assuntos
Anticorpos Antivirais/imunologia , COVID-19/epidemiologia , COVID-19/imunologia , Lúpus Eritematoso Sistêmico/complicações , Lúpus Eritematoso Sistêmico/imunologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Antinucleares/sangue , Anticorpos Antinucleares/imunologia , Anticorpos Antivirais/sangue , Feminino , Humanos , Isotipos de Imunoglobulinas/sangue , Isotipos de Imunoglobulinas/imunologia , Imunossupressores/uso terapêutico , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , SARS-CoV-2
2.
Pan Afr Med J ; 39: 30, 2021.
Artigo em Francês | MEDLINE | ID: mdl-34394821

RESUMO

Diffuse infiltrate lung diseases (DILDs) are frequent in patients with connective tissue diseases. They can be suggestive of connective tissue diseases or occur during follow-up. Antisynthetase syndrome (ASS) is a complex and heterogeneous connective tissue disease. Antisynthetase antibodies, in particular the anti-Jo1 antibody, are found in patients with this syndrome. The prognosis of ASS is conditioned by the occurrence of DILD and its severity, thus guiding therapeutic management. We here report the case of a 57-year-old female patient presenting with acute febrile DILD revealing ASS. Outcome was favorable under bolus corticosteroids in combination with cyclophosphamide treatment.


Assuntos
Anticorpos Antinucleares/imunologia , Doenças Pulmonares Intersticiais/diagnóstico , Miosite/diagnóstico , Corticosteroides/administração & dosagem , Autoanticorpos/imunologia , Ciclofosfamida/administração & dosagem , Feminino , Humanos , Imunossupressores/administração & dosagem , Doenças Pulmonares Intersticiais/tratamento farmacológico , Doenças Pulmonares Intersticiais/etiologia , Pessoa de Meia-Idade , Miosite/complicações , Miosite/imunologia
3.
J Autoimmun ; 123: 102706, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34293683

RESUMO

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


Assuntos
Autoanticorpos/imunologia , Vacinas contra COVID-19/efeitos adversos , COVID-19/prevenção & controle , Cadeias HLA-DRB1/imunologia , Hepatite Autoimune/etiologia , Mitocôndrias/imunologia , SARS-CoV-2/imunologia , Vacinação/efeitos adversos , Animais , Anticorpos Antinucleares/imunologia , Especificidade de Anticorpos , Autoantígenos/imunologia , Linhagem Celular , Técnica Indireta de Fluorescência para Anticorpo , Hepatite Autoimune/tratamento farmacológico , Hepatite Autoimune/imunologia , Hepatite Autoimune/patologia , Humanos , Imunossupressores/uso terapêutico , Fígado/imunologia , Fígado/patologia , Masculino , Pessoa de Meia-Idade , Prednisona/uso terapêutico , Rosuvastatina Cálcica/efeitos adversos , Rosuvastatina Cálcica/uso terapêutico
5.
Medicine (Baltimore) ; 100(9): e24556, 2021 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-33655922

RESUMO

ABSTRACT: Previous studies from various countries have reported anti-dense fine speckled pattern (DFS)70 antibody prevalence but few studies have been from Asia. We investigated the prevalence of anti-DFS70 autoantibodies in a Japanese cohort of healthy individuals (HI) and patients with antinuclear antibody-associated autoimmune rheumatic diseases (AARD).Enzyme-linked immunosorbent assay and indirect immunofluorescence were performed using samples from 250 HI and 276 AARD patients.The overall anti-DFS70 antibody prevalence in HI was 16.4%, with 12.8% for males and 20.0% for females (sex difference; P = .12). In AARD patients, the anti-DFS70 antibody prevalence in systemic lupus erythematosus, mixed connective tissue disease, systemic sclerosis, dermatomyositis and polymyositis (DM/PM), Sjögren syndrome, and rheumatoid arthritis (RA) was 22.1%, 14.3%, 14.3%, 3.0%, 21.3%, and 18.1%, respectively (no significant difference between AARD patients except DM/PM and HI). The prevalence of isolated anti-DFS70 antibody in HI and all AARD patients excluding RA was 14.8% (37/250) and 4.4% (9/204), respectively (P  < .01 vs HI). Among anti-DFS70 antibody-positive cases, 63.4% (26/41) were DFS pattern by IIF and 23.5% (8/34) were HI and AARD patients excluding RA, respectively.The anti-DFS70 antibody prevalence in HI and AARD patients in Japan was similar. Furthermore, the anti-DFS70 antibody prevalence in HI and AARD in Japan is higher than in HI and AARD in regions other than Asia. This makes AARD differential diagnosis by antinuclear antibody screening difficult.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/imunologia , Anticorpos Antinucleares/sangue , Autoanticorpos/sangue , Doenças Autoimunes/sangue , Doenças Reumáticas/sangue , Fatores de Transcrição/imunologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Antinucleares/imunologia , Grupo com Ancestrais do Continente Asiático/estatística & dados numéricos , Autoanticorpos/imunologia , Doenças Autoimunes/imunologia , Ensaio de Imunoadsorção Enzimática , Feminino , Técnica Indireta de Fluorescência para Anticorpo , Humanos , Japão/epidemiologia , Masculino , Pessoa de Meia-Idade , Prevalência , Doenças Reumáticas/imunologia , Adulto Jovem
6.
Ann R Coll Surg Engl ; 103(3): e94-e97, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33645285

RESUMO

Behçet's disease is a rare disease characterised by recurrent oral ulcers, with systemic manifestations including genital ulcers, ocular disease, skin lesions, gastrointestinal disease, neurologic disease, vascular disease and arthritis. Most clinical manifestations of Behçet's disease are believed to be due to vasculitis. The heterogeneous clinical spectrum is influenced by sex, ethnicity and country of residence. Vascular manifestation in the form of isolated large brachial artery aneurysm is rare in children. Treatment involves aneurysmorrhaphy to avoid rupture or ischaemic sequelae in addition to lifelong medical management to control vasculitis.


Assuntos
Aneurisma/diagnóstico por imagem , Síndrome de Behçet/diagnóstico , Artéria Braquial/diagnóstico por imagem , Trombose/diagnóstico por imagem , Aneurisma/etiologia , Aneurisma/patologia , Aneurisma/cirurgia , Anticorpos Antinucleares/imunologia , Síndrome de Behçet/complicações , Síndrome de Behçet/imunologia , Síndrome de Behçet/patologia , Sedimentação Sanguínea , Artéria Braquial/patologia , Artéria Braquial/cirurgia , Proteína C-Reativa/imunologia , Pré-Escolar , Angiografia por Tomografia Computadorizada , Antígeno HLA-B51/imunologia , Humanos , Masculino , Veia Safena/transplante , Trombose/etiologia , Trombose/patologia , Trombose/cirurgia , Enxerto Vascular/métodos
7.
Mol Immunol ; 132: 41-52, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33545624

RESUMO

Pathogens such as the Epstein Barr virus (EBV) have long been implicated in the etiology of systemic lupus erythematosus (SLE). The Epstein Barr virus nuclear antigen I (EBNA-1) has been shown to play a role in the development of anti-nuclear antibodies characteristic of SLE. One mechanism by which EBV may play a role in SLE is molecular mimicry. We previously generated two monoclonal antibodies (mAbs) to EBNA-1 and demonstrated that they cross-react with double-stranded DNA (dsDNA). In the present study, we demonstrate that these mAbs have pathogenic potential. We show that they can bind to isolated rat glomeruli and that binding can be greatly diminished by pretreatment of glomeruli with DNase I, suggesting that these mAbs bind dsDNA in the kidney. We also demonstrate that these antibodies can deposit in the kidney when injected into mice and can induce proteinuria and elicit histopathological alterations consistent with glomerulonephritis. Finally, we show that these antibodies can cross-react with laminin and collagen IV in the extracellular matrix suggesting that direct binding to the glomerular basement membrane or mesangial matrix may also contribute to the antibody deposition in the kidney. In summary, our results indicate that EBNA-1 can elicit antibodies that cross-react with dsDNA, that can deposit in the kidney, and induce kidney damage. These results are significant because they support the role of a viral protein in SLE and lupus nephritis.


Assuntos
Anticorpos Antinucleares/toxicidade , Anticorpos Monoclonais/toxicidade , Anticorpos Antivirais/imunologia , DNA/imunologia , Infecções por Vírus Epstein-Barr/imunologia , Antígenos Nucleares do Vírus Epstein-Barr/imunologia , Glomérulos Renais/imunologia , Animais , Anticorpos Antinucleares/imunologia , Anticorpos Monoclonais/genética , Anticorpos Monoclonais/imunologia , Anticorpos Monoclonais/isolamento & purificação , Colágeno/imunologia , Reações Cruzadas/imunologia , Desoxirribonuclease I , Infecções por Vírus Epstein-Barr/metabolismo , Matriz Extracelular/genética , Matriz Extracelular/imunologia , Feminino , Membrana Basal Glomerular/imunologia , Membrana Basal Glomerular/metabolismo , Glomerulonefrite/imunologia , Glomerulonefrite/patologia , Glomerulonefrite/virologia , Células HEK293 , Humanos , Imunoglobulina G/imunologia , Glomérulos Renais/patologia , Laminina/imunologia , Camundongos , Camundongos Endogâmicos BALB C , Mimetismo Molecular , Proteinúria/imunologia , Ratos , Ratos Sprague-Dawley
8.
Clin Biochem ; 90: 28-33, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33539810

RESUMO

INTRODUCTION: The clinical significance of common antinuclear antibody (ANA) patterns, such as nuclear homogenous and nuclear speckled patterns with their corresponding specific antibodies, has already been established. However, the clinical relevance of these uncommon ANA patterns have not been well elucidated and these patterns are therefore not reported by most clinical laboratories. We herein report some retrospective data analysis linking patients' clinical status to several uncommon ANA patterns. METHODS: We retrieved and assessed the patient records for ANA reports generated in our hospital over a period of two years. All testing had been performed using the gold standard Indirect Immunofluorescence Assay. RESULTS: Records of 1235 consecutive patients tested for ANA were reviewed. ANA was positive in 330 of these patients with 6.39% found to have uncommon nuclear, cytoplasmic or mitotic sub-patterns. The mitotic spindle (0.89%), cytoplasmic anti-mitochondrial antibodies (0.80%), followed by discrete nuclear dots-multiple (0.72%) were the dominating patterns, with a higher prevalence in females than in males. Systemic lupus erythematosus and rheumatoid arthritis were the two most common autoimmune disorders associated with mitotic spindle fibers and nuclear centromere and nuclear large/coarse speckled ANA patterns. CONCLUSION: The prevalence of these relatively uncommon ANA patterns was higher than expected. Further evaluation of these patterns along with their corresponding antibodies and their clinical utility must be encouraged. We trust this endeavour will provide diagnostic information in autoimmune and other disease conditions.


Assuntos
Anticorpos Antinucleares/análise , Doenças Autoimunes/diagnóstico , Adulto , Anticorpos Antinucleares/imunologia , Artrite Reumatoide/imunologia , Doenças Autoimunes/imunologia , Biomarcadores/análise , Feminino , Técnica Indireta de Fluorescência para Anticorpo/métodos , Humanos , Índia , Lúpus Eritematoso Sistêmico/imunologia , Masculino , Mitocôndrias/imunologia , Mitose/imunologia , Proteínas Nucleares/imunologia , Estudos Retrospectivos , Fuso Acromático/imunologia , Centros de Atenção Terciária
9.
Arthritis Rheumatol ; 73(5): 740-749, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33538122

RESUMO

OBJECTIVE: Co-occurrence of autoantibodies specific for ≥1 autoimmune disease is widely prevalent in rheumatoid arthritis (RA) patients. To understand the prevalence of polyautoimmunity in preclinical RA, we performed a comprehensive autoantibody assessment in a First Nations cohort of at-risk first-degree relatives (FDR) of RA patients, a subset of whom subsequently developed RA (progressors). METHODS: Venous blood was collected from all study participants (n = 50 RA patients and 64 FDR) at scheduled visits, and serum was stored at -20°C. High-sensitivity C-reactive protein level, anti-citrullinated protein antibody (ACPA) status, and autoantibody status were determined using commercially available enzyme-linked immunosorbent assay kits. Rheumatoid factor (RF) was detected by nephelometry. Antinuclear autoantibodies (ANA) were identified using Hep-2 indirect immunofluorescence assay (IFA) and classified according to international consensus nomenclature as various anti-cell (AC) patterns. RESULTS: Of our study cohort, 78.9% had positive ANA reactivity (≥1:80), which was either a homogenous, fine-speckled (AC-1 and AC-4) or mixed IFA pattern. Importantly, the AC-4 and mixed ANA patterns were also observed in progressors at the time of disease onset. While all of the RA patients showed a high prevalence of arthritis-associated autoantibodies, they also had a high prevalence of extractable nuclear antigen-positive autoantibodies to other autoantigens. In FDR, we did not observe any increase in serum autoreactivity to nonarthritis autoantigens, either cross-sectionally or in samples collected longitudinally from progressors prior to RA onset. CONCLUSION: While alternative autoimmunity and ANA positivity are widely prevalent in First Nations populations, including asymptomatic, seronegative FDR, expansion of alternative autoimmunity does not occur in parallel with ACPA expansion in FDR and is restricted to patients with established RA.


Assuntos
Anticorpos Anti-Proteína Citrulinada/imunologia , Anticorpos Antinucleares/imunologia , Artrite Reumatoide/imunologia , Doenças Assintomáticas , Proteína C-Reativa/imunologia , Fator Reumatoide/imunologia , Adulto , Autoanticorpos/imunologia , Estudos de Coortes , Família , Feminino , Humanos , Canadenses Indígenas , Masculino , Pessoa de Meia-Idade
10.
BMC Pulm Med ; 21(1): 57, 2021 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-33579248

RESUMO

BACKGROUND: Anti-synthetase syndrome (ASSD) is a chronic autoimmune condition characterized by antibodies directed against an aminoacycl transfer RNA synthetase (ARS) along with a group of clinical features including the classical clinical triad: inflammatory myopathy, arthritis, and interstitial lung disease (ILD). ASSD is highly heterogenous due to different organ involvement, and ILD is the main cause of mortality and function loss, which presents as different patterns when diagnosed. We designed this retrospective cohort to describe the clinical features and disease behaviour of ASSD associated ILD. METHODS: Data of 108 cases of ASSD associated ILD were retrospectively collected in Beijing Chaoyang Hospital from December 2017 to March 2019. Data were obtained from the Electronic Medical Record system. Patients were divided into 5 groups according to distinct aminoacyl tRNA synthetase (ARS) antibodies. RESULTS: Overall, 108 consecutive patients were recruited. 33 were JO-1 positive, 30 were PL-7 positive, 23 were EJ positive, 13 were PL-12 positive and 9 were OJ positive. The JO-1 (+) group had a significant higher rate of mechanic's hand (57.6%) than other 4 groups. Polymyositis/dermatomyositis (PM/DM) was diagnosed in 25 (23.1%) patients and no difference was observed among the 5 groups. The PL-7 (+) group had a higher frequency of UIP pattern (13.3%) than the other 4 groups but the difference was not significant, and the EJ (+) group had the most frequent OP pattern (78.2%), which was significantly higher than the PL-7 (+) (P < 0.001) and PL-12 (+) groups (P = 0.025). The median follow-up time was 10.7 months, during which no patients died. All received prednisone treatment, with or without immunosuppressants. At the 6-month follow-up, 96.3% of all patients (104/108) had a positive response to therapy, the JO-1 (+) and EJ (+) groups had a significantly higher improvement of forced vital capacity than the other 3 groups (P < 0.05), and the PL-7 group had the lowest FVC improvement (P < 0.05). The JO-1 (+) group and EJ (+) group had significantly higher anti-Ro-52 positive occurrence than the other 3 groups (P < 0.05). CONCLUSION: Anti PL-7 antibody had the same frequency as anti-JO-1 in ASSD-ILD, in which the ILD pattern was different with distinct anti-ARS antibodies. Most ASSD-ILD had a positive response to steroid therapies, with or without immunosuppressants. The PL-7 (+) group had the highest occurrence of UIP pattern, and a significantly lower response to therapy.


Assuntos
Autoanticorpos/imunologia , Dermatomiosite/fisiopatologia , Doenças Pulmonares Intersticiais/fisiopatologia , Miosite/fisiopatologia , Adulto , Idoso , Alanina-tRNA Ligase/imunologia , Anticorpos Antinucleares/imunologia , China , Estudos de Coortes , Dermatomiosite/tratamento farmacológico , Dermatomiosite/imunologia , Feminino , Glucocorticoides/uso terapêutico , Glicina-tRNA Ligase/imunologia , Humanos , Fibrose Pulmonar Idiopática/tratamento farmacológico , Fibrose Pulmonar Idiopática/imunologia , Fibrose Pulmonar Idiopática/fisiopatologia , Imunossupressores/uso terapêutico , Isoleucina-tRNA Ligase/imunologia , Doenças Pulmonares Intersticiais/diagnóstico por imagem , Doenças Pulmonares Intersticiais/tratamento farmacológico , Doenças Pulmonares Intersticiais/imunologia , Masculino , Pessoa de Meia-Idade , Miosite/tratamento farmacológico , Miosite/imunologia , Prednisona/uso terapêutico , Prognóstico , Estudos Retrospectivos , Treonina-tRNA Ligase/imunologia , Resultado do Tratamento , Capacidade Vital
11.
Rheumatology (Oxford) ; 60(8): 3904-3912, 2021 08 02.
Artigo em Inglês | MEDLINE | ID: mdl-33437990

RESUMO

OBJECTIVES: ANA are the most extensively used test for the diagnosis of systemic autoimmune diseases. However, testing by indirect immunofluorescence assays (IIFAs) on HEp-2 cells, the gold standard test, is time-consuming and needs expertise. Thus there is a trend to replace it with other automated solid-phase assays directed against specific ANA. Nonetheless, the Hep-2 cell is an autoantigen array and ANA have been classified into 29 types, some of them with no clear association with a specificity to be detected. It is especially in these uncommon patterns where no clinical relationship is found and no antigenic specificity is detected. Here we retrospectively collected clinical data from patients with confirmed uncommon HEp-2 IIFA patterns to search for an associated clinical condition. METHODS: We conducted an observational retrospective study including 608 patients with organ-specific and non-organ-specific autoimmune diseases (OSADs and NOSADs, respectively) with a confirmed rare pattern of ANA detected by IIFA on HEp-2 cells in the routine practice of the Spanish European Autoantibodies Standardization Initiative laboratories. Inclusion criteria are the existence of a minimum follow-up of 2 years and the availability of clinical data. RESULTS: Nuclear patterns were more frequent in SLE (P = 0.001) and SS (P = 0.001), whereas the cytoplasmic ones were significantly higher in SSc (P = 0.022) and inflammatory myositis (P = 0.016). Mitotic patterns did not show any preferences for a specific disease and 62.7% of them corresponded to the nuclear mitotic apparatus pattern (AC-26). The most frequent NOSADs in patients with the AC-26 pattern were SLE (28.6%), SS (11.9%) and RA (11.9%). The cytoplasmic HEp-2 IIFA patterns were equally distributed in both groups of patients. In the OSAD patients there was no predominant pattern, except for AC-6 in primary biliary cholangitis due to Sp-100 antibodies (P < 0.001). CONCLUSION: Detection of infrequent ANA might be a unique finding with no disease-associated specificities and could lead to the suspicion of an autoimmune disease.


Assuntos
Anticorpos Antinucleares/imunologia , Lúpus Eritematoso Sistêmico/imunologia , Escleroderma Sistêmico/imunologia , Síndrome de Sjogren/imunologia , Adulto , Idoso , Artrite Reumatoide/diagnóstico , Artrite Reumatoide/imunologia , Doença Celíaca/diagnóstico , Doença Celíaca/imunologia , Feminino , Técnica Indireta de Fluorescência para Anticorpo , Doença de Graves/diagnóstico , Doença de Graves/imunologia , Doença de Hashimoto/diagnóstico , Doença de Hashimoto/imunologia , Humanos , Lúpus Eritematoso Sistêmico/diagnóstico , Masculino , Pessoa de Meia-Idade , Escleroderma Sistêmico/diagnóstico , Síndrome de Sjogren/diagnóstico , Espanha
13.
BMJ Case Rep ; 14(1)2021 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-33504534

RESUMO

A 47-year-old woman with history of seizure disorder (semiology of seizure unknown), not well controlled with antiepileptic drugs since last 30 years presented with 1-year history of intermittent throbbing headache. On the day prior to admission, she experienced worst headache, followed by loss of consciousness. On regaining consciousness, she had neck pain without any focal neurological deficit, but examination was marked by positive meningeal signs. She had history of oral ulceration, photosensitivity and small joints pain for which no medical consultancy was sought until. Following relevant investigations, this case came out to be moyamoya angiopathy secondary to underlying systemic lupus erythematosus. She was put on immunosuppressive and immunomodulator as per recommendations. Among neurological symptoms, headache improved dramatically without any further seizure recurrence till the 6 months of follow-up.


Assuntos
Hemorragia Cerebral/diagnóstico por imagem , Lúpus Eritematoso Sistêmico/diagnóstico , Doença de Moyamoya/diagnóstico por imagem , Albuminúria , Angiografia Digital , Anticorpos Antinucleares/imunologia , Anticonvulsivantes/uso terapêutico , Antirreumáticos/uso terapêutico , Angiografia Cerebral , Hemorragia Cerebral/etiologia , Epilepsia/complicações , Epilepsia/tratamento farmacológico , Feminino , Glucocorticoides/uso terapêutico , Humanos , Hidroxicloroquina/uso terapêutico , Lúpus Eritematoso Sistêmico/complicações , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Lúpus Eritematoso Sistêmico/imunologia , Angiografia por Ressonância Magnética , Pessoa de Meia-Idade , Doença de Moyamoya/complicações , Tomografia Computadorizada por Raios X
14.
Acta Neurol Scand ; 143(2): 131-139, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32762037

RESUMO

BACKGROUND: Myositis-specific autoantibodies (MSAs) have been found to be present predominantly in patients with idiopathic inflammatory myopathies (IIMs). This study aimed to investigate the prevalence of MSAs and their associated complications in a cohort of patients with IIMs. METHODS: This was a multicentered prospective study. Consecutive adult Chinese patients with IIMs in the regional hospitals in Hong Kong were followed up from July 2016 to January 2018. Clinical characteristics, treatment history, and disease complications were documented. A commercially available immunoblot assay was used to detect the MSAs. RESULTS: Out of the 201 patients studied, at least one MSA was found in 63.2% of patients. The most common among the identified MSAs were the anti-melanoma differentiation-associated gene 5 antibody (anti-MDA5 Ab) and the anti-transcriptional intermediary factor 1-gamma antibody (anti-TIF1-γ Ab) (both 13.9%), followed by anti-Jo-1 antibody (12.4%). Anti-MDA5 was present exclusively in dermatomyositis (DM) and was strongly associated with digital ulcers, amyopathy, and rapidly progressive interstitial lung disease (RP-ILD). Anti-TIF1γ was strongly associated with refractory rash and malignancy. Independent risk factors of RP-ILD included anti-MDA5 (OR 14.5), clinically amyopathic DM (OR 13.9), and history of pulmonary tuberculosis (OR 12.2). Cox regression analysis showed that anti-TIF1γ (HR 3.55), DM (HR 3.82), and family history of cancer (HR 3.40) were independent predictors of malignancy. CONCLUSIONS: MSA testing enables dividing of patients with IIMs into phenotypically homogeneous subgroups and prediction of potentially life-threatening complications.


Assuntos
Autoanticorpos/imunologia , Miosite/imunologia , Adulto , Anticorpos Antinucleares/imunologia , Autoanticorpos/sangue , Biomarcadores/sangue , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Miosite/classificação , Miosite/patologia , Fatores de Transcrição/imunologia
15.
Ann Rheum Dis ; 80(2): 194-202, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33004330

RESUMO

OBJECTIVE: Congenital heart block (CHB) with immune cell infiltration develops in the fetus after exposure to maternal Ro/La autoantibodies. CHB-related serology has been extensively studied, but reports on immune-cell profiles of anti-Ro/La-exposed neonates are lacking. In the current study, we characterised circulating immune-cell populations in anti-Ro/La+mothers and newborns, and explored potential downstream effects of skewed neonatal cell populations. METHODS: In total, blood from mothers (n=43) and neonates (n=66) was sampled at birth from anti-Ro/La+ (n=36) and control (n=30) pregnancies with or without rheumatic disease and CHB. Flow cytometry, microarrays and ELISA were used for characterising cells and plasma. RESULTS: Similar to non-pregnant systemic lupus erythematosus and Sjögren-patients, anti-Ro/La+mothers had altered B-cell subset frequencies, relative T-cell lymphopenia and lower natural killer (NK)-cell frequencies. Surprisingly, their anti-Ro/La exposed neonates presented higher frequencies of CD56dimCD16hi NK cells (p<0.01), but no other cell frequency differences compared with controls. Type I and II interferon (IFN) gene-signatures were revealed in neonates of anti-Ro/La+ pregnancy, and exposure of fetal cardiomyocytes to type I IFN induced upregulation of several NK-cell chemoattractants and activating ligands. Intracellular flow cytometry revealed IFNγ production by NK cells, CD8+ and CD4+ T cells in anti-Ro/La exposed neonates. IFNγ was also detectable in their plasma. CONCLUSION: Our study demonstrates an increased frequency of NK cells in anti-Ro/La exposed neonates, footprints of type I and II IFN and an upregulation of ligands activating NK cells in fetal cardiac cells after type I IFN exposure. These novel observations demonstrate innate immune activation in neonates of anti-Ro/La+pregnancy, which could contribute to the risk of CHB.


Assuntos
Anticorpos Antinucleares/imunologia , Bloqueio Cardíaco/congênito , Interferon gama/imunologia , Células Matadoras Naturais/imunologia , Adulto , Autoanticorpos/sangue , Autoanticorpos/imunologia , Feminino , Bloqueio Cardíaco/embriologia , Bloqueio Cardíaco/imunologia , Humanos , Imunidade Inata/imunologia , Recém-Nascido , Masculino , Gravidez , Complicações na Gravidez/imunologia , Doenças Reumáticas/imunologia
16.
Ann Rheum Dis ; 80(1): 118-127, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33004331

RESUMO

OBJECTIVES: Genomic Risk Scores (GRS) successfully demonstrated the ability of genetics to identify those individuals at high risk for complex traits including immune-mediated inflammatory diseases (IMIDs). We aimed to test the performance of GRS in the prediction of risk for systemic sclerosis (SSc) for the first time. METHODS: Allelic effects were obtained from the largest SSc Genome-Wide Association Study (GWAS) to date (9 095 SSc and 17 584 healthy controls with European ancestry). The best-fitting GRS was identified under the additive model in an independent cohort that comprised 400 patients with SSc and 571 controls. Additionally, GRS for clinical subtypes (limited cutaneous SSc and diffuse cutaneous SSc) and serological subtypes (anti-topoisomerase positive (ATA+) and anti-centromere positive (ACA+)) were generated. We combined the estimated GRS with demographic and immunological parameters in a multivariate generalised linear model. RESULTS: The best-fitting SSc GRS included 33 single nucleotide polymorphisms (SNPs) and discriminated between patients with SSc and controls (area under the receiver operating characteristic (ROC) curve (AUC)=0.673). Moreover, the GRS differentiated between SSc and other IMIDs, such as rheumatoid arthritis and Sjögren's syndrome. Finally, the combination of GRS with age and immune cell counts significantly increased the performance of the model (AUC=0.787). While the SSc GRS was not able to discriminate between ATA+ and ACA+ patients (AUC<0.5), the serological subtype GRS, which was based on the allelic effects observed for the comparison between ACA+ and ATA+ patients, reached an AUC=0.693. CONCLUSIONS: GRS was successfully implemented in SSc. The model discriminated between patients with SSc and controls or other IMIDs, confirming the potential of GRS to support early and differential diagnosis for SSc.


Assuntos
Esclerodermia Difusa/genética , Esclerodermia Limitada/genética , Adulto , Idoso , Anticorpos Antinucleares/imunologia , Artrite Reumatoide/genética , Autoanticorpos/imunologia , Estudos de Casos e Controles , DNA Topoisomerases/imunologia , Grupo com Ancestrais do Continente Europeu , Feminino , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Humanos , Modelos Lineares , Lúpus Eritematoso Sistêmico/genética , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Fatores de Risco , Esclerodermia Difusa/imunologia , Esclerodermia Limitada/imunologia , Escleroderma Sistêmico/genética , Escleroderma Sistêmico/imunologia , Síndrome de Sjogren/genética
17.
Mod Rheumatol ; 31(1): 171-176, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32013651

RESUMO

OBJECTIVE: Multiple cytokine network may control the pathogenesis of vasculopathy in patients with systemic sclerosis (SSc). We aimed at comparing angiogenic cytokine profile among SSc patients at various clinical stage. METHODS: We divided nine patients with anti-centromere antibody (ACA) who were suspected of SSc and diagnosed as having SSc into three groups (group1: pre-clinical stage of SSc, group2: mild/early SSc and group3: typical lcSSc) according to the ACR/EULAR2013 classification criteria or ACR1980 preliminary classification, and serum sample were obtained from them. We evaluated the expression levels of 20 cytokines by membrane array. RESULTS: Average values of EGF, ENA-78, bFGF, IGF-I, IL-8, MCP-1, TGF-ß1, thrombopoietin, VEGF and VEGF-D in group2 were increased compared as those of group1 more than twofold. Statistically significant difference was found in serum levels of IGF-1, RANTES and VEGF between group1 and group2. There was also significant difference in the value of VEGF between group1 and group3. There were mild and significant correlations between serum IGF-1 and RANTES levels (r = 0.721, p = .028). CONCLUSION: IGF-1, RANTES and VEGF are thought to be involved in the disease development from pre-clinical stage of SSc to early/mild SSc. Thus, these cytokines may be utilized as a biomarker for early diagnosis.


Assuntos
Anticorpos Antinucleares/imunologia , Quimiocina CCL5/sangue , Fator de Crescimento Insulin-Like I/metabolismo , Escleroderma Sistêmico/sangue , Fator A de Crescimento do Endotélio Vascular/sangue , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Escleroderma Sistêmico/imunologia , Escleroderma Sistêmico/patologia , Regulação para Cima
18.
Ann Hematol ; 100(2): 345-352, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33165625

RESUMO

Immune thrombocytopenia (ITP) can coexist with autoimmune thyroid disease. However, the detailed clinical features remain unknown. We retrospectively reviewed 248 patients with newly diagnosed ITP in our institute for whom we had thyroid function data at diagnosis between 2000 and 2019. Of the 248 patients with ITP, 74 patients also had thyroid disease, including 36 with overt thyroid disease (13 Graves' disease and 23 Hashimoto's thyroiditis) and 38 with subclinical thyroid disease (3 hyperthyroidism and 35 hypothyroidism). ITP and thyroid disease were concurrently diagnosed in 54 patients. Female sex and positivity for antinuclear antibodies (ANA) were significantly associated with thyroid diseases. Platelet-associated immunoglobulin G (PAIgG) levels in patients with Graves' disease were higher than those in patients with Hashimoto's thyroiditis. Platelet counts were similar among euthyroid patients and patients with thyroid disease. Thrombopoietin-receptor agonist was administered more frequently in patients with thyroid disease. The cumulative incidences of thrombosis and bleeding and overall survival did not differ between patients with and without thyroid disease. Treatment for thyroid disease in 22 patients improved thrombocytopenia in 21 patients, especially in 4 patients who were not treated for ITP. This study demonstrated that thyroid diseases were commonly found in patients with ITP. Treatment of the underlying thyroid disease may improve thrombocytopenia.


Assuntos
Púrpura Trombocitopênica Idiopática , Doenças da Glândula Tireoide , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Antinucleares/sangue , Anticorpos Antinucleares/imunologia , Plaquetas/imunologia , Plaquetas/metabolismo , Plaquetas/patologia , Feminino , Humanos , Imunoglobulina G/sangue , Imunoglobulina G/imunologia , Masculino , Pessoa de Meia-Idade , Contagem de Plaquetas , Púrpura Trombocitopênica Idiopática/sangue , Púrpura Trombocitopênica Idiopática/tratamento farmacológico , Púrpura Trombocitopênica Idiopática/imunologia , Receptores de Trombopoetina/agonistas , Receptores de Trombopoetina/sangue , Receptores de Trombopoetina/imunologia , Estudos Retrospectivos , Doenças da Glândula Tireoide/sangue , Doenças da Glândula Tireoide/tratamento farmacológico , Doenças da Glândula Tireoide/imunologia
19.
Arthritis Rheumatol ; 73(5): 816-825, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33225631

RESUMO

OBJECTIVE: To investigate long-term safety and tolerability of anifrolumab, a human monoclonal antibody to the type I interferon (IFN) receptor subunit 1, in patients with moderate-to-severe systemic lupus erythematosus (SLE). METHODS: This 3-year, multinational, open-label extension study included adult patients who completed treatment (48 weeks of anifrolumab or placebo; 12-week follow-up) in the MUSE phase IIb randomized controlled trial (RCT). Patients initially received 1,000 mg of anifrolumab intravenously every 4 weeks, which was reduced to 300 mg every 4 weeks based on the benefit/risk profile established in the MUSE trial. Adverse events (AEs) were assessed monthly. Exploratory end points included the SLE Disease Activity Index 2000 (SLEDAI-2K), Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SDI), pharmacodynamics, and health-related quality of life (HRQoL). RESULTS: Of the 246 patients who completed the RCT, 218 (88.6%) enrolled in the open-label extension study, of which 139 (63.8%) completed 3 years of treatment. Approximately 69.7% of patients reported ≥1 AE during the first year of open-label extension treatment. Frequency and patterns of serious AEs and AEs of special interest over 3 years were consistent with those reported for 1 year of treatment in the RCT. Few patients (6.9%) discontinued treatment due to AEs. No new safety signals were identified. Improvement in the SLEDAI-2K was sustained over 3 years. SDI and Short Form 36 health survey scores remained stable. Neutralization of type I IFN gene signatures was maintained in the IFN-high population, and C3, C4, and anti-double-stranded DNA showed trends toward sustained improvement. CONCLUSION: Long-term anifrolumab treatment demonstrates an acceptable safety profile with sustained improvement in SLE disease activity, HRQoL, and serologic measures.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Antirreumáticos/uso terapêutico , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Adulto , Anticorpos Antinucleares/imunologia , Bronquite/induzido quimicamente , Complemento C3/imunologia , Complemento C4/imunologia , Feminino , Cefaleia/induzido quimicamente , Humanos , Estudos Longitudinais , Lúpus Eritematoso Sistêmico/imunologia , Lúpus Eritematoso Sistêmico/fisiopatologia , Masculino , Pessoa de Meia-Idade , Nasofaringite/induzido quimicamente , Infecções Respiratórias/etiologia , Resultado do Tratamento
20.
Clin Biochem ; 89: 38-43, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33307059

RESUMO

OBJECTIVE: To investigate the clinical significance of perinuclear anti-neutrophil cytoplasmic antibody (p-ANCA) in patients with systemic lupus erythematosus (SLE). METHODS: This retrospective study included 120 SLE patients. All patients were divided into group p-ANCA+ and group p-ANCA-. Demographic characteristics, clinical symptoms, autoantibodies, laboratory tests and renal pathology were compared between these two groups. RESULTS: Among 120 patients, 45 (37.5%) patients were p-ANCA+ and 75 (62.5%) patients were p-ANCA-. The occurrence of lupus nephritis was significantly higher in group p-ANCA+ (P = 0.046). For autoantibodies, the occurrences of anti-dsDNA, anti-nucleosome and anti-histone were significantly higher in group p-ANCA+ (P < 0.001, P = 0.004 and P = 0.006, respectively). Titers of anti-dsDNA antibody, erythrocyte sedimentation rate (ESR), serum beta-2-microglobulin (ß2-MG) and systemic lupus erythematosus disease activity index (SLEDAI) were higher in group p-ANCA+ (P < 0.001, P = 0.021, P < 0.001 and P = 0.005, respectively), while albumin was significantly lower than p-ANCA- group (P = 0.012). There were no differences in the classification of lupus nephritis, activity index and chronicity index. p-ANCA correlated with lupus nephritis, anti-dsDNA antibody, anti-nucleosome antibody and anti-histone antibody, and also disease activity markers, such as titers of anti-dsDNA antibody, ESR, albumin, serum ß2-MG and SLEDAI. CONCLUSION: The appearance of p-ANCA in SLE indicated high probability of lupus nephritis and more severe condition.


Assuntos
Anticorpos Anticitoplasma de Neutrófilos/imunologia , Anticorpos Antinucleares/imunologia , Autoanticorpos/imunologia , Lúpus Eritematoso Sistêmico/patologia , Adulto , Anticorpos Anticitoplasma de Neutrófilos/sangue , Anticorpos Antinucleares/sangue , Autoanticorpos/sangue , Sedimentação Sanguínea , Feminino , Humanos , Testes Imunológicos , Lúpus Eritematoso Sistêmico/sangue , Lúpus Eritematoso Sistêmico/imunologia , Masculino , Estudos Retrospectivos , Índice de Gravidade de Doença
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