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1.
Mod Rheumatol ; : 1-13, 2020 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-31955618

RESUMO

Juvenile dermatomyositis is the most common type of juvenile idiopathic inflammatory myopathy mainly affecting the skin and proximal muscles. We have published the Japanese version of 'Clinical practice guidance for juvenile dermatomyositis (JDM) 2018 'consisting of a review of articles in the field and evidence-informed consensus-based experts' opinion on the treatment strategy in collaboration with The Pediatric Rheumatology Association of Japan and The Japan College of Rheumatology under the financial support by 'Research on rare and intractable diseases, Health and Labor Sciences Research Grants'. This article is a digest version of the Japanese guidance.

2.
Pediatr Int ; 61(11): 1168-1169, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31721373
3.
Pediatr Rheumatol Online J ; 17(1): 17, 2019 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-31039807

RESUMO

BACKGROUND: To investigate efficacy and safety of intravenous abatacept in Japanese patients with active polyarticular-course juvenile idiopathic arthritis (pJIA). METHODS: In this phase III, open-label, multicenter, single-arm study, patients with pJIA aged 4-17 years who failed ≥1 biologic or methotrexate received weight-tiered (< 75 kg: 10 mg/kg; 75-100 kg: 750 mg; > 100 kg: 1000 mg) intravenous abatacept at Weeks 0, 2, 4, and every 4 weeks thereafter. The study comprised a short-term period (16 weeks) and ongoing long-term period. Primary endpoint: Week 16 JIA-American College of Rheumatology criteria 30 (JIA-ACR30) response rate. Secondary endpoints/outcomes included Week 16 JIA-ACR50/70/90 response and inactive disease rates, Childhood Health Assessment Questionnaire-Disability Index (CHAQ-DI), pharmacokinetics, safety, and immunogenicity. Proportions of patients achieving Juvenile Arthritis Disease Activity Score in 27 joints using C-reactive protein (JADAS27-CRP) remission (score < 1) and minimal disease activity (MDA; score < 3.8), were among exploratory endpoints. RESULTS: All 20 patients who received study medication completed the short-term period. During the long-term period, two patients discontinued due to insufficient efficacy or patient decision. Median age and disease duration at baseline were 10.5 and 0.75 years, respectively. Week 16 JIA-ACR30 response rate (primary endpoint) was 90.0% (18/20). JIA-ACR50/70/90 response and inactive disease rates at Week 16 were 75.0% (15/20), 70.0% (14/20), 35.0% (7/20), and 25.0% (5/20), respectively. At Week 52, JIA-ACR30/50/70/90 response and inactive disease rates were observed by 88.9% (16/18), 88.9% (16/18), 83.3% (15/18), 66.7% (12/18) and 44.4% (8/18), respectively. CHAQ-DI improved after Week 12. JADAS27-CRP remission and MDA were achieved by 15.0% (3/20) and 45.0% (9/20) of patients at Week 16, and by 50.0% (9/18) and 78.0% (14/18) of patients at Week 52, respectively. The mean abatacept pre-dose serum concentration was above the target therapeutic exposure (10 µg/ml) from Week 8 through Week 16. All adverse events were of mild/moderate intensity, except for one case of severe gastroenteritis. No deaths, malignancies, or autoimmune disorders were observed. No antidrug antibodies were detected through Week 16; one patient had a positive immunogenic response during the cumulative period. CONCLUSION: Intravenous abatacept was efficacious and well tolerated in Japanese patients with active pJIA. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01835470 . Date of registration: April 19, 2013.


Assuntos
Abatacepte/administração & dosagem , Antirreumáticos/administração & dosagem , Artrite Juvenil/tratamento farmacológico , Abatacepte/efeitos adversos , Abatacepte/farmacocinética , Adolescente , Antirreumáticos/efeitos adversos , Antirreumáticos/farmacocinética , Criança , Pré-Escolar , Feminino , Humanos , Infusões Intravenosas , Masculino , Fatores de Tempo , Resultado do Tratamento
4.
Clin Immunol ; 203: 9-13, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30951839

RESUMO

Immune dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome is one of the inborn errors of immunity, characterized by impaired function of the regulatory T cells. Clinical manifestations of IPEX syndrome are characterized by various autoimmune diseases with autoantibodies. The comprehensive analysis for autoantibodies using human proteome microarrays in the four patients with IPEX syndrome was performed. The numbers of the highly expressed autoantibody showing relative log2 ratios greater than 1 were 1876, 513, 234 and 831 (mean: 864), respectively. Some novel autoantibodies which could explain the phenotypes of patients, adrenal dysfunction, muscular hypotonia, afibrinogenemia, enteropathy and pancytopenia were identified. Various kinds of autoantibodies targeting testis-specific antigens were also identified. Human proteome microarray is a powerful tool to understand the pathophysiology of IPEX syndrome. The larger cohort analysis using this method will provide further understanding of the impaired immune tolerance in humans.

6.
Mod Rheumatol ; 29(1): 130-133, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29529894

RESUMO

OBJECTIVES: The purpose of this study is to evaluate systemic disease activity of pediatric Sjögren's syndrome (SS) using European League Against Rheumatism (EULAR) Sjögren's syndrome disease activity index (ESSDAI). METHODS: We retrospectively reviewed medical records of patients with SS who have been diagnosed according to 1999 Japanese diagnostic criteria for SS before 16 years old at KKR Sapporo Medical Center, Hokkaido University Hospital, and affiliated hospitals. We analyzed clinical and laboratory data and calculated ESSDAI at both diagnosis and peak activity. RESULTS: Twenty-five patients (2 boys and 23 girls) were enrolled. Only 4 patients had sicca symptoms at diagnosis. Mean ESSDAI scores at diagnosis and peak activity were 12.68 (2-31) and 15.08 (2-38), respectively. Only 3 patients were inactive (ESSDAI score <5) at diagnosis. Frequently involved domains at diagnosis were the biological (96%) followed by the constitutional (68%), glandular (44%), articular (44%), cutaneous domains (28%), renal (16%), and central nervous system (12%). At peak activity, biological domain (96%) was followed by the constitutional (72%), glandular (60%), articular (44%), cutaneous (28%), central nervous system (20%), and renal domains (16%). CONCLUSION: Pediatric SS is suspected from active systemic manifestations. The items of ESSDAI are useful clues to the diagnosis of pediatric SS.


Assuntos
Síndrome de Sjogren , Adolescente , Fatores Etários , Criança , Feminino , Humanos , Japão/epidemiologia , Masculino , Gravidade do Paciente , Projetos de Pesquisa , Estudos Retrospectivos , Índice de Gravidade de Doença , Síndrome de Sjogren/diagnóstico , Síndrome de Sjogren/epidemiologia , Síndrome de Sjogren/fisiopatologia
7.
Mod Rheumatol ; 29(2): 351-356, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29532710

RESUMO

OBJECTIVES: The aim of our study is to clarify the association of myositis-specific autoantibodies (MSAs) with clinical and laboratory features in Japanese patients with juvenile idiopathic inflammatory myopathies (JIIMs). METHODS: We retrospectively analyzed the frequency of MSAs and their association with clinical or laboratory findings in 25 Japanese patients with JIIMs in Hokkaido district. RESULTS: Eighteen of the 25 patients (72%) were positive for MSAs; seven with anti-melanoma differentiation associated gene (MDA) 5 (28%), five with anti-transcriptional intermediary factor (TIF)-1γ (20%), four with anti-MJ/nuclear matrix protein (NXP)-2 (16%), two with anti-Jo-1 (8%), one with anti- HMG-CoA reductase, one with anti-signal recognition peptide (SRP) antibodies (4% each), including co-existence and transition of MSAs in one patient each. Anti-MDA5 antibodies were related to interstitial lung disease (ILD) and arthritis but not to amyopathic juvenile dermatomyositis. Drug-free remission was achieved, once ILD was overcome in this group. Anti-TIF-1γ antibodies were associated with typical rashes and mild myositis. Anti-MJ/NXP2 and anti-SRP antibodies were associated with severe muscle weakness. No patient was complicated with malignancy. CONCLUSION: Anti-MDA5 antibodies are prevalent and closely associated with ILD in our series compared with other countries. There was no apparent difference in clinical features associated with other MSAs among races.


Assuntos
Artrite , Autoanticorpos , Helicase IFIH1 Induzida por Interferon/imunologia , Doenças Pulmonares Intersticiais , Miosite , Adolescente , Artrite/epidemiologia , Artrite/etiologia , Artrite/imunologia , Autoanticorpos/sangue , Autoanticorpos/classificação , Criança , Pré-Escolar , Correlação de Dados , Proteínas de Ligação a DNA/imunologia , Feminino , Histidina-tRNA Ligase/imunologia , Humanos , Hidroximetilglutaril-CoA Redutases/imunologia , Japão/epidemiologia , Doenças Pulmonares Intersticiais/epidemiologia , Doenças Pulmonares Intersticiais/etiologia , Doenças Pulmonares Intersticiais/imunologia , Masculino , Miosite/complicações , Miosite/imunologia , Miosite/fisiopatologia , Prevalência , Estudos Retrospectivos , Fatores de Transcrição/imunologia
8.
J Allergy Clin Immunol ; 142(6): 1818-1830.e6, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-29704593

RESUMO

BACKGROUND: Regulatory T (Treg) cells play a crucial role in peripheral immune tolerance in multiple organs, including the skin. Thus far, the effect of peripheral immune tolerance failure on autoantibody-related autoimmune reactions to the skin is unclear. OBJECTIVE: We sought to elucidate the target autoantigens in the skin under the condition of Treg cell dysfunction caused by forkhead box P3 (Foxp3) gene mutations in scurfy mice and patients with immunodysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome. METHODS: Sera and skin from scurfy mice and sera from patients with IPEX syndrome were analyzed to detect target autoantigens by using immunofluorescence studies, ELISAs, and immunoblotting. The pathogenicity of scurfy IgG was examined by using a passive transfer experiment. CD4+ T cells from scurfy mice were transferred to immunodeficient mice to examine their pathogenicity. Signal transducer and activator of transcription 6 (Stat6)-/- scurfy mice were analyzed to further clarify the molecular pathway of autoantibody production. Follicular helper T-cell counts are measured in Stat6-/- scurfy mice and scurfy mice. RESULTS: Scurfy mice spontaneously generated IgG autoantibodies to the dermal-epidermal junction, which had been class-switched from IgM within 12 days after birth. The target autoantigens were murine BP230 and type XVII collagen (COL17). The scurfy polyclonal autoantibodies did not induce skin fragility in neonatal mice. Autoantibody production was induced by CD4+ T cells from scurfy mice and was ameliorated by Stat6 gene knockout in association with a decrease of follicular helper T cells. We also identified autoantibodies to COL17 and BP230 in patients with IPEX syndrome and found an association between production of autoantibodies to COL17 and an eczematous skin phenotype. CONCLUSIONS: Dysregulation of Treg cells generates autoantibodies to COL17 and BP230 in vivo.


Assuntos
Autoanticorpos/imunologia , Autoantígenos/imunologia , Colágeno Tipo VII/imunologia , Diabetes Mellitus Tipo 1/congênito , Diarreia/imunologia , Distonina/imunologia , Doenças Genéticas Ligadas ao Cromossomo X/imunologia , Doenças do Sistema Imunitário/congênito , Linfócitos T Reguladores/imunologia , Animais , Diabetes Mellitus Tipo 1/imunologia , Feminino , Fatores de Transcrição Forkhead/genética , Humanos , Doenças do Sistema Imunitário/imunologia , Imunoglobulina G/imunologia , Masculino , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Fator de Transcrição STAT6/genética
9.
J Allergy Clin Immunol ; 141(3): 1036-1049.e5, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-29241729

RESUMO

BACKGROUND: Immunodysregulation polyendocrinopathy enteropathy x-linked (IPEX) syndrome is a monogenic autoimmune disease caused by FOXP3 mutations. Because it is a rare disease, the natural history and response to treatments, including allogeneic hematopoietic stem cell transplantation (HSCT) and immunosuppression (IS), have not been thoroughly examined. OBJECTIVE: This analysis sought to evaluate disease onset, progression, and long-term outcome of the 2 main treatments in long-term IPEX survivors. METHODS: Clinical histories of 96 patients with a genetically proven IPEX syndrome were collected from 38 institutions worldwide and retrospectively analyzed. To investigate possible factors suitable to predict the outcome, an organ involvement (OI) scoring system was developed. RESULTS: We confirm neonatal onset with enteropathy, type 1 diabetes, and eczema. In addition, we found less common manifestations in delayed onset patients or during disease evolution. There is no correlation between the site of mutation and the disease course or outcome, and the same genotype can present with variable phenotypes. HSCT patients (n = 58) had a median follow-up of 2.7 years (range, 1 week-15 years). Patients receiving chronic IS (n = 34) had a median follow-up of 4 years (range, 2 months-25 years). The overall survival after HSCT was 73.2% (95% CI, 59.4-83.0) and after IS was 65.1% (95% CI, 62.8-95.8). The pretreatment OI score was the only significant predictor of overall survival after transplant (P = .035) but not under IS. CONCLUSIONS: Patients receiving chronic IS were hampered by disease recurrence or complications, impacting long-term disease-free survival. When performed in patients with a low OI score, HSCT resulted in disease resolution with better quality of life, independent of age, donor source, or conditioning regimen.


Assuntos
Diabetes Mellitus Tipo 1/congênito , Diarreia , Fatores de Transcrição Forkhead , Doenças Genéticas Ligadas ao Cromossomo X , Transplante de Células-Tronco Hematopoéticas , Doenças do Sistema Imunitário/congênito , Imunossupressão , Mutação , Adolescente , Adulto , Aloenxertos , Criança , Pré-Escolar , Diabetes Mellitus Tipo 1/genética , Diabetes Mellitus Tipo 1/imunologia , Diabetes Mellitus Tipo 1/mortalidade , Diabetes Mellitus Tipo 1/terapia , Diarreia/genética , Diarreia/imunologia , Diarreia/mortalidade , Diarreia/terapia , Intervalo Livre de Doença , Feminino , Seguimentos , Fatores de Transcrição Forkhead/genética , Fatores de Transcrição Forkhead/imunologia , Doenças Genéticas Ligadas ao Cromossomo X/genética , Doenças Genéticas Ligadas ao Cromossomo X/imunologia , Doenças Genéticas Ligadas ao Cromossomo X/mortalidade , Doenças Genéticas Ligadas ao Cromossomo X/terapia , Humanos , Doenças do Sistema Imunitário/genética , Doenças do Sistema Imunitário/imunologia , Doenças do Sistema Imunitário/mortalidade , Doenças do Sistema Imunitário/terapia , Lactente , Masculino , Estudos Retrospectivos , Taxa de Sobrevida
10.
Mod Rheumatol ; 28(1): 108-113, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-28612674

RESUMO

OBJECTIVES: Acute leukemia often causes osteoarthralgia. The aim of this study is characterization of leukemia-associated osteoarthralgia in comparison with juvenile idiopathic arthritis (JIA). METHODS: We retrospectively reviewed clinical records of 31 patients with acute leukemia and 13 patients with articular JIA diagnosed between January 2008 and March 2013. Clinical and laboratory findings at the initial examination were compared among the three groups; 10 leukemia with and 21 leukemia without osteoarthralgia and 13 JIA groups. RESULTS: Eleven of the 31 leukemic patients (35%) had osteoarthralgia before the diagnosis of leukemia. Peripheral leukemic cells were initially absent in 10 of the 31 leukemia patients including three with osteoarthralgia. Platelet counts over 300 × 109/L were common in JIA, but not in osteoarthralgia group. Mean serum lactate dehydrogenase levels were higher in both of the leukemia groups than JIA group but often within normal or near-normal levels in the leukemia groups. Magnetic resonance imaging was examined in three leukemic patients and demonstrated osteomyelitis-like bone marrow edema in two and periarticular infiltration similar to synovitis in one patient. Three leukemic patients with osteoarthralgia showed partial and transient responses to antibiotic therapy. CONCLUSIONS: Leukemia-associated osteoarthralgia is often indistinguishable from rheumatic diseases by imaging and laboratory findings and should be confirmed by bone marrow examination.


Assuntos
Artralgia/diagnóstico por imagem , Artrite Juvenil/diagnóstico por imagem , Medula Óssea/diagnóstico por imagem , Edema/diagnóstico por imagem , Leucemia/diagnóstico por imagem , Dor/diagnóstico por imagem , Artralgia/etiologia , Criança , Pré-Escolar , Diagnóstico Diferencial , Feminino , Humanos , Leucemia/complicações , Imagem por Ressonância Magnética/métodos , Masculino , Dor/etiologia , Estudos Retrospectivos
11.
Mod Rheumatol ; 28(2): 365-368, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26457478

RESUMO

Palindromic rheumatism (PR), a rare disease in children, is characterized by recurrent arthritis or periarthritis and asymptomatic interval. We report evolution of PR to juvenile idiopathic arthritis in a Japanese girl with heterozygous complex L110P-E148Q allele of MEFV gene. Poor response to colchicine alone suggests that the MEFV substitution could increase the susceptibility to arthritis rather than caused arthritis associated with atypical Familial Mediterranean Fever. Weekly methotrexate is a choice for such cases.


Assuntos
Artrite Juvenil/complicações , Artrite Reumatoide/etiologia , Mutação , Pirina/genética , Antirreumáticos/uso terapêutico , Artrite Juvenil/tratamento farmacológico , Artrite Juvenil/genética , Artrite Juvenil/patologia , Artrite Reumatoide/tratamento farmacológico , Artrite Reumatoide/genética , Artrite Reumatoide/patologia , Pré-Escolar , Colchicina/uso terapêutico , Feminino , Heterozigoto , Humanos
12.
Tokai J Exp Clin Med ; 42(2): 79-84, 2017 Jul 20.
Artigo em Inglês | MEDLINE | ID: mdl-28681367

RESUMO

In recent years, there have been many reports about the efficacy of stenting for central bronchial stenosis. When central bronchial stenosis is due to metastasis of a malignant tumor to the trachea and/or bronchi (endobronchial metastasis: EM), it is classified as "narrow EM" and "broad EM." [1] We managed two patients in whom bilateral stent placement was required for narrow and broad EM arising from colorectal cancer. Case 1: In September 2011, a 66-year-old man underwent low anterior resection for advanced colorectal cancer associated with unresectable liver metastasis. The liver metastasis became resectable after chemotherapy, with two resection procedures and radiofrequency ablation (RFA) being performed. Thereafter, lung metastasis occurred and a tumor in the left lung was resected. In May 2015, he developed respiratory distress. CT identified multiple lesions protruding into the lumen of the trachea and the left and right main bronchi. There was no evidence of mediastinal relapse or local relapse at the resection margin, and tumors were only detected in the tracheobronchial walls. Accordingly, narrow EM was diagnosed. An expandable metallic stent (EMS) was placed on the right side where stenosis was more severe, and radiation therapy was conducted for the non-stented tumors. The patient died 8 months later. Case 2: A 69-year-old woman had undergone laparoscopic right hemicolectomy and adjuvant chemotherapy for Stage lllb cancer of the ascending colon. Due to subsequent elevation of tumor markers, PET-CT was conducted and abnormal uptake was seen in the apex of the right lung and right upper abdomen. Both lesions were resected, and omental and lung metastases were diagnosed. She received treatment with UFT / calcium folinate, but relapse occurred at the resection margin in the right lung. At 7 years and 5 months after initial surgery, she complained of respiratory distress at an outpatient visit. CT demonstrated displacement of the trachea and right main bronchus due to enlargement of upper mediastinal lymph nodes. There was also severe stenosis of the right main bronchus due to tumor infiltration. Because there was both infiltration from local recurrence after resection and upper mediastinal lymph node enlargement, broad EM was diagnosed. An EMS was placed at the site of severe stenosis in the right main bronchus. Similar to Case 1, radiation therapy was also conducted, but respiratory distress occurred after 3 months due to tumor re-growth at the stent margin. Accordingly, stent-in-stent placement was performed and her respiratory symptoms improved. However, superior vena cava syndrome occurred 1 month later and the patient died. We consider that placing an EMS is effective in patients with tracheal stenosis due to EM that is judged to be an oncological emergency.


Assuntos
Neoplasias Brônquicas/secundário , Neoplasias Brônquicas/terapia , Neoplasias Colorretais/patologia , Stents , Estenose Traqueal/terapia , Idoso , Neoplasias Brônquicas/complicações , Evolução Fatal , Feminino , Humanos , Masculino , Metais , Estenose Traqueal/etiologia , Resultado do Tratamento
14.
Clin Immunol ; 174: 24-31, 2017 01.
Artigo em Inglês | MEDLINE | ID: mdl-27856304

RESUMO

Heterozygous dominant-negative mutations of STAT1 are responsible for autosomal-dominant Mendelian susceptibility to mycobacterial diseases (AD-MSMD). So far, only 7 mutations have been previously described and are localized to 3 domains: the DNA-binding domain, the SH2 domain, and the tail segment. In this study, we demonstrated the first coiled-coil domain (CCD) mutation of c.749G>C, p.G250A (G250A) in STAT1 as a genetic cause of AD-MSMD in a patient with mycobacterial multiple osteomyelitis. This de novo heterozygous mutation was shown to have a dominant-negative effect on the gamma-activated sequence (GAS) transcriptional activity following IFN-γ stimulation, which could be attributable to the abolished phosphorylation of STAT1 from the wild-type (WT) allele. The three-dimensional structure of STAT1 revealed the G250 residue was located distant from a cluster of residues affected by gain-of-function mutations responsible for chronic mucocutaneous candidiasis.


Assuntos
Predisposição Genética para Doença , Infecções por Mycobacterium/genética , Fator de Transcrição STAT1/genética , Pré-Escolar , Feminino , Humanos , Mutação , Domínios Proteicos
15.
Front Neurorobot ; 11: 67, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29311889

RESUMO

Humans divide perceived continuous information into segments to facilitate recognition. For example, humans can segment speech waves into recognizable morphemes. Analogously, continuous motions are segmented into recognizable unit actions. People can divide continuous information into segments without using explicit segment points. This capacity for unsupervised segmentation is also useful for robots, because it enables them to flexibly learn languages, gestures, and actions. In this paper, we propose a Gaussian process-hidden semi-Markov model (GP-HSMM) that can divide continuous time series data into segments in an unsupervised manner. Our proposed method consists of a generative model based on the hidden semi-Markov model (HSMM), the emission distributions of which are Gaussian processes (GPs). Continuous time series data is generated by connecting segments generated by the GP. Segmentation can be achieved by using forward filtering-backward sampling to estimate the model's parameters, including the lengths and classes of the segments. In an experiment using the CMU motion capture dataset, we tested GP-HSMM with motion capture data containing simple exercise motions; the results of this experiment showed that the proposed GP-HSMM was comparable with other methods. We also conducted an experiment using karate motion capture data, which is more complex than exercise motion capture data; in this experiment, the segmentation accuracy of GP-HSMM was 0.92, which outperformed other methods.

19.
J Rheumatol ; 42(12): 2412-8, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26472413

RESUMO

OBJECTIVE: Rapidly progressive interstitial lung disease (RP-ILD) is an intractable and fatal complication of juvenile dermatomyositis (JDM). This study evaluated serum levels of B cell activating factor (BAFF) and a proliferation-inducing ligand (APRIL) in JDM patients with complicating ILD, and their association with ILD phenotypes, clinical variables, and anti-melanoma differentiation-associated gene 5 (MDA5). METHODS: We measured the levels of BAFF, APRIL, and anti-MDA5 in the sera of 23 JDM patients with ILD [8 in the RP-ILD group and 15 in the chronic ILD (C-ILD) group], 17 JDM patients without ILD (non-ILD group), and 10 age-matched controls, using the ELISA method. ILD was identified by high-resolution computed tomography. RESULTS: Serum BAFF titers were significantly higher in the JDM patients with RP-ILD versus those with C-ILD (p = 0.011) and in healthy controls (p = 0.0004). The C-ILD group had significantly higher levels of BAFF versus controls (p ≤ 0.0001). Serum APRIL was markedly elevated in the RP-ILD group as compared with the C-ILD group (p = 0.003) and controls (p = 0.006). In patients with ILD, both BAFF and APRIL levels were correlated with serum Krebs von den Lungen-6 and interleukin 18. Subjects with high titer anti-MDA5 (> 200 U) had higher levels of BAFF and APRIL than those with low titer anti-MDA5 (< 100 U; p = 0.019 and p = 0.0029, respectively), which may have been due to a relationship between RP-ILD and high anti-MDA5 titer. CONCLUSION: Our findings of markedly elevated levels of BAFF and APRIL in patients with RP-ILD JDM suggest the potential importance of these cytokines in the diagnosis and treatment of RP-ILD accompanying JDM.


Assuntos
Fator Ativador de Células B/sangue , Dermatomiosite/sangue , Dermatomiosite/epidemiologia , Doenças Pulmonares Intersticiais/sangue , Doenças Pulmonares Intersticiais/epidemiologia , Membro 13 da Superfamília de Ligantes de Fatores de Necrose Tumoral/sangue , Biomarcadores/sangue , Estudos de Casos e Controles , Criança , Pré-Escolar , Comorbidade , Dermatomiosite/fisiopatologia , Progressão da Doença , Feminino , Hospitais Universitários , Humanos , Japão , Doenças Pulmonares Intersticiais/fisiopatologia , Masculino , Valor Preditivo dos Testes , Prognóstico , Valores de Referência , Medição de Risco , Índice de Gravidade de Doença , Estatísticas não Paramétricas
20.
Artigo em Japonês | MEDLINE | ID: mdl-26213192

RESUMO

Failure of the immunotolerance mechanisms causes multiple organ-specific autoimmune disorders. Mutations of autoimmune regulator (AIRE) gene result in central immunotolerance deficiency named autoimmune polyendocrinopathy, candidiasis, ectodermal dystrophy (APECED). Mutations of FOXP3 genes cause regulatory T cell (Treg) deficiency named immune dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome. Because T cell tolerance influences B cell tolerance, autoantibodies seem to reflect the presence of autoreactive T cells with the same antigen specificity. To date many differences in both clinical features and autoantibody profiles have been described between APECED and IPEX syndrome. In addition to the differences in target organs, we have found differences in the target antigens in the same organ, small intestine, between both disorders; anti-autoimmune enteropathy-related 75 kDa antigen (AIE-75) antibodies are specific to IPEX syndrome, whereas anti-tryptophan hydroxylase-1 (TPH-1) antibodies are specific to APECED. These facts suggest that immunotolerance to AIE-75 depends on the Treg, whereas the tolerance to TPH-1 depends on the central mechanisms. Furthermore, given the earlier onset and more serious clinical features of IPEX syndrome than APECED, physiological roles of Aire on the selection of Treg may be, if present, limited.


Assuntos
Autoantígenos/imunologia , Tolerância Imunológica/imunologia , Autoanticorpos/imunologia , Doenças Autoimunes/imunologia , Linfócitos B/imunologia , Diabetes Mellitus Tipo 1/congênito , Diabetes Mellitus Tipo 1/imunologia , Diarreia/imunologia , Doenças Genéticas Ligadas ao Cromossomo X/imunologia , Humanos , Doenças do Sistema Imunitário/congênito , Doenças do Sistema Imunitário/imunologia , Neuroimunomodulação/imunologia , Poliendocrinopatias Autoimunes/imunologia , Linfócitos T/imunologia
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