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1.
Clin Chem Lab Med ; 62(12): 2461-2468, 2024 Nov 26.
Artigo em Inglês | MEDLINE | ID: mdl-38753471

RESUMO

OBJECTIVES: Even in the current era of hematology analyzer automation and peripheral equipment, quality control sample measurement remains a manual task, leading to variability in quality control data and increased workload. In this study, we evaluated the performance of quality control measurement using the BT-50 Transportation Unit (BT-50, Sysmex, Kobe, Japan), equipped with a scheduled automatic quality control function, to ensure measurement accuracy and streamline the workflow of hematology testing. METHODS: We evaluated the automatic measurement performance of quality control samples using the BT-50 for six representative blood test parameters: WBC (white blood cell), RBC (red blood cell), HGB (hemoglobin), HCT (hematocrit), PLT (platelet), and RET% (reticulocyte percent). We evaluated the equivalence and compared measurement accuracy between the BT-50 and the manual method. We then compared the variability to other laboratories and confirmed the stability of quality control samples. We also evaluated changes in workflow and staff resources before and after the introduction of the BT-50. RESULTS: The quality control measurement results for the BT-50 and the manual method were found to be equivalent for all six parameters. The variability measured by the BT-50 was lower for some parameters compared to the manual method. Furthermore, the workflow was streamlined by reducing manual processes, resulting in increased efficiency. CONCLUSIONS: We confirmed the performance of quality control measurements using the schedule function of the BT-50. Introducing the BT-50 reduced the operator's workload, improved operational efficiency, and promoted the standardization of quality control measurements.


Assuntos
Controle de Qualidade , Humanos , Automação , Testes Hematológicos/normas , Testes Hematológicos/métodos , Automação Laboratorial/normas
2.
Hepatol Res ; 2024 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-38806293

RESUMO

AIM: Shear wave (SW) elastography is used to evaluate metabolic dysfunction-associated steatotic liver disease (MASLD) pathophysiology. Increased elasticity due to fibrosis and increased viscosity due to necrosis and inflammation affect SW. Assessing fibrosis, the most prognostically relevant pathology, is critical. Viscosity is evaluated using the dispersion slope (DS); however, cut-off values that affect SW values are unclear. We compared the ultrasound imaging parameters (SW for viscoelasticity; DS for viscosity) with pathological findings. METHODS: Patients (n = 159) who underwent liver biopsy and SW and DS assessments at our hospital were included. Fibrosis stage and inflammation grade cut-off values were calculated from SW, DS, and liver biopsy results using receiver operating characteristic curves. Cases in which liver biopsy results were inconsistent with SW results were used to determine the effect of viscosity on SW values. DS was examined in the Correct and Incorrect Diagnosis groups, which were categorized based on the concordance between SW and liver biopsy results. Dispersion slope cut-off values between the two groups were calculated. RESULTS: Fibrosis stage cut-off values by SW (m/s) were: ≥F2, 1.62; ≥F3, 1.74; and F4, 1.97. Inflammation grade cut-off values by DS (m/s/kHz) were: ≥A1, 11.6; ≥A2, 14.5; and A3, 16.1. The Correct/Incorrect Diagnosis groups had 25/70 patients. The DS cut-off value for both groups was 13.2 m/s/kHz. CONCLUSIONS: Shear wave and DS are useful for evaluating liver fibrosis and inflammation in MASLD. For DS > 13.2 m/s/kHz, SW may be affected by the increased viscosity owing to inflammation. In such patients, caution should be used when determining/interpreting values.

3.
Rheumatology (Oxford) ; 61(5): 2006-2015, 2022 05 05.
Artigo em Inglês | MEDLINE | ID: mdl-34498053

RESUMO

OBJECTIVES: This study aimed to quantify nailfold capillary (NFC) abnormalities in anti-melanoma differentiation-associated gene 5 (MDA5) -positive DM patients and to evaluate the association with clinical parameters, including serum biomarkers. In addition, we aimed to clarify the period leading to remission of NFC abnormalities during immunosuppressive treatment in patients with DM. METHODS: A prospective observational study was conducted including patients (n = 10) who first visited Hiroshima University Hospital and were diagnosed with DM or clinically amyopathic DM with anti-MDA5 antibodies. We compared the NFC abnormalities detected by nailfold-video capillaroscopy (NVC), physical findings, blood tests, respiratory function tests, and vascular-related growth factors measured using a LEGENDplexTM Multi-Analyte Flow Assay Kit. RESULTS: NFC abnormalities improved in all patients from 2 to 17 weeks after the initiation of immunosuppressive treatment. The NVC scores were inversely correlated with anti-MDA5 antibody titres at baseline. NVC scores and forced vital capacity were positively correlated. Baseline values of M-CSF and stem cell factor were correlated with anti-MDA-5 titres. CONCLUSION: Our study suggested that NVC scores and disease activity were inversely correlated before treatment. Vascular-related growth factors, such as M-CSF and stem cell factor, may be associated with the disease mechanism in patients with anti-MDA5 antibody-positive DM.


Assuntos
Dermatomiosite , Miosite , Autoanticorpos , Capilares/anormalidades , Dermatomiosite/complicações , Humanos , Imunossupressores/uso terapêutico , Helicase IFIH1 Induzida por Interferon , Fator Estimulador de Colônias de Macrófagos , Miosite/complicações , Fator de Células-Tronco , Malformações Vasculares
4.
Pathobiology ; 89(2): 92-100, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-34802006

RESUMO

INTRODUCTION: Lipopolysaccharide (LPS) contamination of commercially available proteins has seriously impeded research on citrullinated fibrinogen (cit-Fb) in rheumatoid synovial cells (RSCs). METHODS: RSCs obtained from 4 rheumatoid arthritis patients who underwent full knee arthroplasty were cultured, stimulated with cit-Fb, and cytokine expression levels were measured. We then evaluated polymyxin-B (PMB), heat inactivation, and rough (R)-type LPS mutants for rapid detection of LPS contamination. RESULTS: cit-Fb induced expression of CXCL10 and IFNB in RSCs via the toll-like receptor. PMB inhibited cit-Fb-mediated CXCL10 gene expression but not protein expression induced by 20 µg/mL cit-Fb. Heat inactivation did not affect LPS-mediated CXCL10 or IL-6 induction; however, cit-Fb-mediated CXCL10expression was inhibited. Wild-type LPS from Escherichia coli (WT-LPS) strongly induces CXCL10 expression, but induction by Ra-LPS was weak, and induction by Rc- and Re-LPS was minimal. Re-LPS suppression of WT-LPS-mediated CXCL10 induction in RSCs and peripheral blood monocytes (PBMs) was dose dependent. Furthermore, Re-LPS completely suppressed cit-Fb-mediated CXCL10 induction in RSCs and PBMs. CONCLUSION: To easily identify LPS contamination during routine experiments, our results suggest that Re-LPS is a better tool for rapid detection of LPS contamination compared to PMB and heat treatment.


Assuntos
Artrite Reumatoide , Lipopolissacarídeos , Artrite Reumatoide/diagnóstico , Artrite Reumatoide/genética , Artrite Reumatoide/metabolismo , Técnicas de Cultura de Células , Células Cultivadas , Citocinas , Humanos , Lipopolissacarídeos/farmacologia , Monócitos
5.
Mod Rheumatol ; 32(1): 141-148, 2022 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-33775207

RESUMO

OBJECTIVES: Cyclophosphamide (CYC) has been proposed as a standard induction regimen for interstitial lung disease (ILD) associated with systemic sclerosis (SSc). However, there remain patients with SSc-ILD who are intractable to the therapy. This study aimed to identify factors associated with inadequate response to CYC and investigate how to treat SSc-ILD, especially in the need for glucocorticoids (GCs) combined with CYC. METHODS: This retrospective study included consecutive patients diagnosed with SSc-ILD and treated with CYC between 2009 and 2020. Logistic regression models were used to determine the prognostic factors indicating significant progression of ILD (SP-ILD). The clinical findings of patients treated with vs. without GCs were compared. RESULTS: Nineteen patients were registered, with a median age of 61.0 years. Fifteen were females, and five were classified into SP-ILD. Baseline high C-reactive protein (CRP) levels and non-widespread or localized ground-glass opacities (GGOs) predicted SP-ILD in multivariable analyses, and the cut-off level of CRP was 0.41 mg/dL. In clinical courses, SSc-ILD with high inflammation temporarily responded to CYC, regardless of the combined use of GCs; however, the therapeutic effects deteriorated soon after stopping CYC. CONCLUSION: High CRP levels with non-widespread GGO predicted progressive ILD in patients with SSc treated with CYC.


Assuntos
Doenças Pulmonares Intersticiais , Escleroderma Sistêmico , Proteína C-Reativa , Ciclofosfamida/uso terapêutico , Feminino , Glucocorticoides/uso terapêutico , Humanos , Imunossupressores/uso terapêutico , Pulmão , Doenças Pulmonares Intersticiais/complicações , Doenças Pulmonares Intersticiais/diagnóstico por imagem , Doenças Pulmonares Intersticiais/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Escleroderma Sistêmico/complicações , Escleroderma Sistêmico/tratamento farmacológico
6.
Mod Rheumatol ; 31(4): 803-808, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33325280

RESUMO

OBJECTIVE: To retrospectively evaluate whether oral glucocorticoid (GC) administration can be tapered or discontinued over a 2-year observation period in patients with rheumatoid arthritis (RA) undergoing a stable oral GC treatment, without deterioration in the disease status. METHODS: Methotrexate (MTX) and prednisolone (PSL) dosages were increased and decreased, respectively, to the maximum extent possible. Concomitant biological or targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARDs) were used as required. Changes in PSL and MTX use and disease status were evaluated at baseline (BL), year-1, and year-2. RESULTS: Thirty-six patients were enrolled (median age, 65.4 years; disease duration, 7.1 years). The proportion of patients using PSL decreased over 2 years (100-13.9%, p < .0001). While no change was observed in the proportion of patients using MTX, the average administered dose increased at year-1 (p = .06). Moreover, b/tsDMARDs were administered in nine patients (two in year-1, seven in year-2). The Clinical Disease Activity Index remission rate increased from 25.0% to 38.9%. Serious adverse events were identified in two patients. CONCLUSIONS: Oral GC administration was discontinued without deterioration in the rheumatoid arthritis disease control.


Assuntos
Antirreumáticos/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Glucocorticoides/uso terapêutico , Metotrexato/uso terapêutico , Prednisolona/uso terapêutico , Idoso , Quimioterapia Combinada , Feminino , Glucocorticoides/administração & dosagem , Humanos , Masculino , Pessoa de Meia-Idade , Prednisolona/administração & dosagem , Estudos Retrospectivos , Suspensão de Tratamento
7.
Mod Rheumatol ; 31(3): 643-648, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-32815450

RESUMO

OBJECTIVES: Lupus enteritis (LE) is a rare but well-known gastrointestinal manifestation of systemic lupus erythematosus (SLE). This study was conducted to identify prognostic factors associated with poor responses in patients with LE. METHODS: We consecutively registered patients diagnosed with LE between January 2009 and October 2019, and retrospectively compared their clinical characteristics based on whether they had good or poor responses to treatment. RESULTS: A total of 13 patients (17 episodes) were included. The median age was 41 years, and 12 patients were female. A comparison of clinical characteristics between groups revealed similar computed tomography (CT) findings. However, serum CH50 levels were significantly lower in the poor response group (median [interquartile ranges (IQR)]; 29.2 [25.3-46.9] U/mL vs 19.3 [7.8-24.0] U/mL, p = .0095). More patients in the poor response group had higher titers of anti-cardiolipin ß2-glycoprotein I antibody (anti-CL ß2GPI Ab) and were started on glucocorticoids (GCs) at moderate doses. In multivariable analysis, serum CH50 level was independently associated with poor response to induction therapy. CONCLUSION: Lower levels of CH50 at the time of initial treatment predicted inadequate treatment response in patients with LE.


Assuntos
Ensaio de Atividade Hemolítica de Complemento/normas , Enterite/tratamento farmacológico , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Adulto , Autoanticorpos/imunologia , Enterite/sangue , Enterite/diagnóstico por imagem , Feminino , Glucocorticoides/administração & dosagem , Glucocorticoides/uso terapêutico , Humanos , Lúpus Eritematoso Sistêmico/sangue , Lúpus Eritematoso Sistêmico/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Tomografia Computadorizada por Raios X , beta 2-Glicoproteína I/imunologia
8.
Clin Exp Rheumatol ; 38(5): 956-963, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31969227

RESUMO

OBJECTIVES: This study aimed to identify therapeutic predictors of abatacept (ABT) treatment in rheumatoid arthritis (RA) in vitro and in patients. METHODS: T cell cytokine, monokine, and chemokine levels in culture supernatants or serum were determined using flow cytometry bead-based immunoassays. CXCL10 mRNA and protein expressions were also assessed using qPCR and ELISA analyses, respectively. In the patient study, 25 ABT-treated patients were analysed retrospectively. The patients were divided into low disease activity (LDA) or non-low disease activity (non-LDA) groups at 24 weeks of ABT treatment. Seven T cell cytokines and CXCL10 levels were compared in these two groups. RESULTS: Peripheral blood mononuclear cells (PBMC) from healthy donors were stimulated by immobilised anti-CD3 with or without ABT for three days, and the levels of 13 T cell cytokines in culture supernatants were determined. ABT significantly inhibited anti-CD3-induced production of IFN-γ. To examine the effect of these T cell cytokines in rheumatoid synovial cells (RSC), RSCs were stimulated with 10% of culture supernatants from anti-CD3-stimulated PBMCs with or without ABT, and the levels of 23 cytokines were determined. Only CXCL10 was significantly reduced by ABT-treated supernatants. In the patient study, CXCL10 levels at baseline were not different between the LDA and non-LDA groups, whereas CXCL10 levels at 24 weeks were significantly decreased in the LDA group only. CONCLUSIONS: ABT treatment significantly affected IFN-γ and CXCL10 cytokine levels in vitro. In addition, serum CXCL10 levels were associated with better responses in ABT treatment.


Assuntos
Artrite Reumatoide , Leucócitos Mononucleares , Abatacepte/farmacologia , Artrite Reumatoide/tratamento farmacológico , Quimiocina CXCL10 , Quimiocinas , Humanos , Estudos Retrospectivos
9.
Pathobiology ; 87(3): 198-207, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32126552

RESUMO

OBJECTIVE: Activin A is known to be highly expressed in rheumatoid synovium. In the present study, we investigated the effect of inflammatory cytokines on activin A production and its role in rheumatoid inflammation using freshly prepared rheumatoid synovial cells (fresh-RSC). METHODS: Fresh-RSC from patients with rheumatoid arthritis were obtained and stimulated with multiple cytokines for activin A production. Gene expression levels of activin A and inflammatory cytokines were determined by quantitative PCR (qPCR) analysis. An enzyme-linked immunosorbent assay (ELISA) was used to measure activin A and CXCL10 in culture supernatants. The osteoclasts generated from human peripheral monocytes by RANKL stimulation were identified by tartrate-resistant acid phosphatase staining and bone resorption assay using Osteo plate. The expression levels of NFATc1 and cathepsin K, critical intracellular proteins for osteoclastogenesis, were determined by Western blotting. RESULTS: Activin A production in fresh-RSC was markedly enhanced by the synergistic effect of TGF-ß1 with inflammatory cytokines, including TNFα, IL-1ß, and IL-6. Activin A inhibited TNFα-induced CXCL10, an important chemoattractant for pathogen-activated T cells and monocytes of osteoclast precursors, but it did not affect the expression of inflammatory cytokines and chemokines. In addition, activin A directly inhibited the expression of NFATc1 and cathepsin K, as well as osteoclast formation in human samples. CONCLUSION: Our data indicated that TGF-ß1 is involved in the expression of activin A at inflamed joints. Activin A mainly exerts an anti-inflammatory action, which prevents joint damage via the regulation of CXCL10 and osteoclastogenesis.


Assuntos
Ativinas/genética , Quimiocina CXCL10/genética , Cápsula Articular/citologia , Osteogênese , Fator de Necrose Tumoral alfa/genética , Diferenciação Celular , Células Cultivadas , Citocinas/imunologia , Regulação para Baixo , Humanos , Cápsula Articular/imunologia , Leucócitos Mononucleares/imunologia , Fator de Necrose Tumoral alfa/imunologia
10.
Int J Mol Sci ; 21(3)2020 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-31991837

RESUMO

Osteoclasts are multinucleated giant cells responsible for bone resorption. Various mediators involved in osteoclast differentiation have been investigated as possible therapeutic targets for osteoporosis and rheumatoid arthritis (RA). Although transforming growth factor beta1 (TGFß1) has been described as one such multifunctional cytokine essential for bone remodeling, its effect on osteoclastogenesis remains controversial. Therefore, we sought to examine the effect of TGFß1 on osteoclast generation induced by receptor activator of nuclear factor (NF)-κB ligand (RANKL) in humans. Peripheral blood monocytes, isolated using magnetic bead sorting, were cultured with macrophage-colony stimulating factor (M-CSF) or RANKL with or without TGFß1. Tartrate-resistant acid phosphatase (TRAP) staining, as well as bone resorption assays, revealed that TGFß1 suppressed RANKL-mediated human osteoclast development. Real-time reverse transcription PCR and Western blotting revealed that TGFß1 reduced the gene and protein expression of nuclear factor of activated T cells, cytoplasmic 1 (NFATc1), the master regulator of osteoclast differentiation, respectively. Luciferase assays indicated that TGFß1 inhibited the NF-κB p65-stimulated promoter activity of NFATc1. Immunofluorescence analysis demonstrated that TGFß1 abrogated RANKL-induced nuclear translocation of p65. Thus, TGFß1 regulates human RANKL-induced osteoclastogenesis via downregulation of NFATc1 by blocking nuclear translocation of NF-κB, suggesting that TGFß1 may be a potential therapeutic target for RA.


Assuntos
Regulação da Expressão Gênica , Fatores de Transcrição NFATC/genética , Osteogênese , Ligante RANK/metabolismo , Fator de Crescimento Transformador beta1/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores , Reabsorção Óssea/genética , Reabsorção Óssea/metabolismo , Diferenciação Celular/genética , Células Cultivadas , Feminino , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Imunofenotipagem , Leucócitos Mononucleares/citologia , Leucócitos Mononucleares/efeitos dos fármacos , Leucócitos Mononucleares/metabolismo , Masculino , Pessoa de Meia-Idade , Modelos Biológicos , Osteoclastos/citologia , Osteoclastos/metabolismo , Osteogênese/efeitos dos fármacos , Osteogênese/genética , Regiões Promotoras Genéticas , Transporte Proteico , Ligante RANK/farmacologia , Fator de Crescimento Transformador beta1/farmacologia
13.
ScientificWorldJournal ; 2016: 2597376, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27403452

RESUMO

Nucleotide-binding oligomerization domain-containing protein (Nod) 2 is an intracellular pattern recognition receptor, which recognizes muramyl dipeptide (N-Acetylmuramyl-L-Alanyl-D-Isoglutamine: MDP), a bacterial peptidoglycan component, and makes a NF-κB-activating complex called nodosome with adaptor protein RICK (RIP2/RIPK2). Nod2 mutants are associated with the autoinflammatory diseases, Blau syndrome (BS)/early-onset sarcoidosis (EOS). For drug discovery of BS/EOS, we tried to develop Nod2-nodosome in a cell-free system. FLAG-tagged RICK, biotinylated-Nod2, and BS/EOS-associated Nod2 mutants were synthesized, and proximity signals between FLAG-tagged and biotinylated proteins were detected by amplified luminescent proximity homogeneous assay (ALPHA). Upon incubation with MDP, the ALPHA signal of interaction between Nod2-WT and RICK was increased in a dose-dependent manner. The ALPHA signal of interaction between RICK and the BS/EOS-associated Nod2 mutants was more significantly increased than Nod2-WT. Notably, the ALPHA signal between Nod2-WT and RICK was increased upon incubation with MDP, but not when incubated with the same concentrations, L-alanine, D-isoglutamic acid, or the MDP-D-isoform. Thus, we successfully developed Nod2-nodosome in a cell-free system reflecting its function in vivo, and it can be useful for screening Nod2-nodosome-targeted therapeutic molecules for BS/EOS and granulomatous inflammatory diseases.


Assuntos
Artrite/metabolismo , Sistema Livre de Células , Descoberta de Drogas , Proteína Adaptadora de Sinalização NOD2/metabolismo , Sarcoidose/metabolismo , Sinovite/metabolismo , Uveíte/metabolismo , Acetilmuramil-Alanil-Isoglutamina/metabolismo , Artrite/patologia , Humanos , Sarcoidose/patologia , Sinovite/patologia , Uveíte/patologia
14.
Mod Rheumatol ; 26(5): 681-4, 2016 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-26709121

RESUMO

OBJECTIVES: We aimed to investigate the frequency of moderate-to-severe sleep apnea syndrome (SAS) that possibly influences long-term prognosis in patients with rheumatoid arthritis (RA), and to analyze the risk factors for this group. METHODS: We examined respiratory disturbance index (RDI) by polysomnography in 62 hospitalized RA patients. Risk factors of moderate-to-severe SAS (RDI ≥20) were analyzed using a multivariate logistic regression analysis. RESULTS: RA was complicated by moderate-to-severe SAS in 13/62 (20.9%) cases. The highest stage of temporomandibular joint abnormality (TMJA) and a high value of health assessment questionnaire-disability index (HAQ-DI) were significant risk factors, according to the results of the multivariate logistic regression analysis (p < 0.0001 and p = 0.010, respectively). Contrary to these results, RDI was not related to the disease activity indexes of RA and other clinical characteristics. CONCLUSION: We clarified that the highest TMJA stage and a high value of HAQ-DI are novel important risk factors for moderate-to-severe SAS in RA patients.


Assuntos
Artrite Reumatoide/complicações , Síndromes da Apneia do Sono/complicações , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Prognóstico , Fatores de Risco , Índice de Gravidade de Doença , Síndromes da Apneia do Sono/diagnóstico
15.
Mol Biol Rep ; 41(1): 545-53, 2014 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-24318677

RESUMO

Familial Mediterranean fever (FMF) is a recessive inherited autoinflammatory syndrome. Patients with FMF have symptoms such as recurrent fever and abdominal pain, sometimes accompanied by arthralgia. Biopsy specimens have revealed substantial neutrophil infiltration into synovia. FMF patients have a mutation in the Mediterranean fever gene, encoding pyrin, which is known to regulate the inflammasome, a platform for processing interleukin (IL)-1ß. FMF patients heterozygous for E148Q mutation, heterozygous for M694I mutation, or combined heterozygous for E148Q and M694I mutations, which were found to be major mutations in an FMF study group in Japan, suffer from arthritis, the severity of which is likely to be lower than in FMF patients with M694V mutations. Expression plasmids of wild-type (WT) pyrin and mutated pyrin, such as E148Q, M694I, M694V, and E148Q+M694I, were constructed, and SW982 synovial sarcoma cells were transfected with these expression plasmids. IL-8 and IL-6 were spontaneously secreted from the culture supernatant of SW982 cells without any stimulation, whereas IL-1ß and TNF-α could not be detected even when stimulated with lipopolysaccharide. Notably, two inflammasome components, ASC and caspase-1, could not be detected in SW982 cells by Western blotting. IL-8 but not IL-6 secretion from SW982 cells was largely suppressed by WT pyrin, but less suppressed by mutated pyrin, which appeared to become weaker in the order of E148Q, M694I, E148Q+M694I, and M694V mutations. As for IL-8 and IL-6, similar results were obtained using stable THP-1 cells expressing the WT pyrin or mutated pyrins, such as M694V or E148Q, when stimulated by LPS. In addition, IL-8 secretion from mononuclear cells of FMF patients was significantly higher than that of healthy volunteers when incubated on a culture plate. Thus, our results suggest that IL-8 secretion from SW982 synovial sarcoma cells suppressed by pyrin independently of inflammasome is affected by pyrin mutations, which may reflect the activity in FMF arthritis.


Assuntos
Proteínas do Citoesqueleto/genética , Febre Familiar do Mediterrâneo/genética , Inflamassomos/metabolismo , Interleucina-8/metabolismo , Proteínas Adaptadoras de Sinalização CARD , Caspase 1/metabolismo , Linhagem Celular Tumoral , Citocinas/metabolismo , Proteínas do Citoesqueleto/metabolismo , Regulação para Baixo , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Febre Familiar do Mediterrâneo/imunologia , Febre Familiar do Mediterrâneo/metabolismo , Estudos de Associação Genética , Células HEK293 , Humanos , Leucócitos Mononucleares/metabolismo , Mutação de Sentido Incorreto , Fosforilação , Processamento de Proteína Pós-Traducional , Pirina , Sarcoma Sinovial , Solubilidade
16.
Mod Rheumatol ; 24(1): 137-43, 2014 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-24261770

RESUMO

OBJECTIVES: Anti-cytokine therapy is reportedly useful in amyloid A (AA) amyloidosis complicating rheumatic diseases. However, to date no studies have directly compared the utility of tumour necrosis factor (TNF) inhibition to that of interleukin-6. The aim of our retrospective study was to compare the clinical utility of tocilizumab (TCZ) and anti-TNF (TNF inhibitor) therapy. METHODS: We studied 42 patients treated with anti-cytokine agents at our hospital: 31 had received a single agent, ten had received two agents and one had received three agents. Patients were divided into a TCZ group (22 patients) and a TNF inhibitor group (32 patients). The main parameters compared were treatment retention rate, serum amyloid A (SAA) profile, renal function profile and clinical disease activity index. RESULTS: The 5-year retention rates were 90.4 (TCZ group) and 34.3 % (TNF inhibitor group) (p = 0.0154, log-rank test). The median SAA fell from 219.2 µg/mL at treatment initiation to 5.0 µg/mL at last observation (TCZ), and from 143.6 to 38.1 µg/mL (TNF inhibitor) (p = 0.0194). Estimated glomerular filtration rate was improved in 72.7 (TCZ) and 34.4 % (TNF inhibitor) of patients (p = 0.0062). The rates of clinical remission or low disease activity at last observation for the TCZ and TNF inhibitor groups were 72.7 and 40.7 % (p = 0.0201), respectively. CONCLUSIONS: Based on these results, we conclude that TCZ was of greater clinical utility than anti-TNF therapy in our patients with AA amyloidosis complicating rheumatic diseases.


Assuntos
Amiloidose/tratamento farmacológico , Anticorpos Monoclonais Humanizados/uso terapêutico , Antirreumáticos/uso terapêutico , Doenças Reumáticas/tratamento farmacológico , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Idoso , Amiloidose/complicações , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Doenças Reumáticas/complicações , Resultado do Tratamento
17.
Clin Rheumatol ; 43(10): 3195-3204, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39134873

RESUMO

We aimed to clarify the long-term safety and efficacy of rituximab (RTX) as a remission induction therapy following severe relapse in patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). We retrospectively collected the data of patients with severely relapsed AAV from a Japanese multicentre cohort. The primary exposure was RTX use; the primary outcome was complete remission (CR) proportions at week 24. Baseline characteristics were compared between the RTX and non-RTX groups. We performed multivariate logistic regression analysis and one-to-one propensity score matching analysis as a sensitivity analysis. Totally, 100 patients were enrolled: 52 in the RTX group and 48 in the non-RTX group. Baseline characteristics were comparable between the two groups, except for age, AAV subtype and ANCA serotype. The median age was 71 vs. 75 years, and the PR3-ANCA positivity rate was 44.2% vs. 18.8% in the RTX and non-RTX groups, respectively. No significant difference was observed in CR proportions at week 24 between the two groups (79.2% vs. 68.1%, p = 0.321), with an adjusted odds ratio of 1.27 (95% confidence interval [CI] 0.47-3.51). At week 48, CR proportions were significantly higher in the RTX group (91.7% vs. 64.9%, p = 0.005), with an adjusted odds ratio of 2.95 (95% CI 0.97-9.91). Serious infection rates were lower in the RTX group than in the non-RTX group, with no statistically significant difference. RTX was not superior to conventional immunosuppressive therapies at week 24 but showed significantly favourable results at week 48 for severely relapsed AAV.


Assuntos
Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos , Recidiva , Indução de Remissão , Rituximab , Humanos , Rituximab/uso terapêutico , Rituximab/efeitos adversos , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/tratamento farmacológico , Feminino , Masculino , Estudos Retrospectivos , Idoso , Japão , Pessoa de Meia-Idade , Resultado do Tratamento , Idoso de 80 Anos ou mais , Antirreumáticos/uso terapêutico , População do Leste Asiático
18.
Mod Rheumatol Case Rep ; 7(1): 108-112, 2023 01 03.
Artigo em Inglês | MEDLINE | ID: mdl-35950798

RESUMO

The direct causes of dermatomyositis, a common autoimmune disease, have not yet been accurately identified, but several studies have linked this condition to various patient-associated and environmental factors, such as viral infections and area of residence. In the present report, we describe our experience with a patient presenting with anti-melanoma differentiation-associated gene 5 (MDA5) antibody-positive dermatomyositis, which developed after vaccination against coronavirus disease 2019 (COVID-19). This patient was simultaneously diagnosed with anti-glutamic acid decarboxylase antibody-positive slowly progressive insulin-dependent diabetes (SPIDDM); her human leucocyte antigen test revealed that she expressed the DRB1*04:05 allele. This is important as this genotype is known to increase susceptibility to both anti-MDA5 antibody-positive dermatomyositis and type I diabetes. To the best of our knowledge, this is the first case of dermatomyositis complicated by SPIDDM identified after COVID-19 vaccination against COVID-19 and presenting with an underlying susceptible genotype. The patient's genetic predisposition may also be important for the development of autoimmune disease after COVID-19 vaccination.


Assuntos
Doenças Autoimunes , Vacinas contra COVID-19 , COVID-19 , Dermatomiosite , Diabetes Mellitus , Doenças Pulmonares Intersticiais , Feminino , Humanos , Autoanticorpos , Doenças Autoimunes/complicações , COVID-19/diagnóstico , COVID-19/prevenção & controle , COVID-19/complicações , Vacinas contra COVID-19/efeitos adversos , Dermatomiosite/etiologia , Dermatomiosite/complicações
19.
Viruses ; 15(7)2023 07 03.
Artigo em Inglês | MEDLINE | ID: mdl-37515185

RESUMO

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes coronavirus disease 2019 (COVID-19), utilizes the host receptor angiotensin-converting enzyme 2 (ACE2) and the auxiliary receptor Neuropilin-1 (NRP1) to enter host cells. NRP1 has another isoform, NRP2, whose function in COVID-19 has seldom been reported. In addition, although patients with severe cases of COVID-19 often exhibit increased levels of proinflammatory cytokines, the relationship between these cytokines and SARS-CoV-2 proliferation remains unknown. The aim of this study is to clarify the roles of proinflammatory cytokines in Neuropilin expressions and in SARS-CoV-2 infection. To identify the expression patterns of NRP under inflamed and noninflamed conditions, next-generation sequencing (RNA-seq), immunohistochemistry, quantitative real-time PCR, and Western blotting were performed using primary cultured fibroblast-like synoviocytes, MH7A (immortalized cell line of human rheumatoid fibroblast-like synoviocytes), immortalized MRC5 (human embryonic lung fibroblast), and synovial tissues. To measure viral proliferative capacity, SARS-CoV-2 infection experiments were also performed. NRP2 was upregulated in inflamed tissues. Cytokine-stimulated human fibroblast cell lines, such as MH7A and immortalized MRC5, revealed that NRP2 expression increased with co-stimulation of tumor necrosis factor α (TNFα) and interleukin-1 beta (IL-1ß) and was suppressed with anti-TNFα antibody alone. TNFα and IL-1ß promoted SARS-CoV-2 proliferation and Spike protein binding. The viral proliferation coincided with the expression of NRP2, which was modulated through plasmid transfections. Our results revealed that proinflammatory cytokines, including TNFα, contribute to NRP2 upregulation and SARS-CoV-2 proliferation in host human cells.


Assuntos
COVID-19 , SARS-CoV-2 , Humanos , Proliferação de Células , Citocinas , Interleucina-1beta , SARS-CoV-2/metabolismo , Glicoproteína da Espícula de Coronavírus/genética , Glicoproteína da Espícula de Coronavírus/metabolismo , Fator de Necrose Tumoral alfa/farmacologia
20.
Mod Rheumatol Case Rep ; 8(1): 49-54, 2023 Dec 29.
Artigo em Inglês | MEDLINE | ID: mdl-37718611

RESUMO

This case report describes a 52-year-old immunocompromised man diagnosed with disseminated Mycobacterium abscessus complex (MABC) infection. The patient had a history of malignant lymphoma and presented with fever and polyarthritis that lasted 3 weeks. Upon initial evaluation, blood and synovial fluid cultures from the swollen joints were negative. Reactive arthritis or rheumatoid arthritis was suspected as the cause of inflammatory synovitis in multiple joints. Administration of prednisolone followed by an interleukin-6 inhibitor improved the fever, but polyarthritis persisted, and destruction of the left hip joint was observed. Two months later, M. abscessus was detected in a blood culture and right shoulder joint synovium, leading to a final diagnosis of disseminated MABC infection. The joint symptoms resolved with combined antimicrobial therapy using amikacin, azithromycin, and imipenem/cilastatin. To date, 12 cases of disseminated MABC infection with osteoarticular manifestations have been reported. A total of 13 cases, including the present case, were reviewed. Seven patients had bone involvements, five had joint involvement, and the remaining one had bursa involvement. All the cases with joint involvement, except for our case, presented with monoarthritis. MABC infection is diagnosed based on the demonstration of MABC itself. Clinicians should keep disseminated MABC infection in mind as a possible cause of persistent arthritis. As demonstrated in our case, multiple replicate cultures of blood or specimens from the affected sites may be needed to detect it.


Assuntos
Artrite , Infecções por Mycobacterium não Tuberculosas , Mycobacterium abscessus , Masculino , Humanos , Pessoa de Meia-Idade , Diagnóstico Diferencial , Infecções por Mycobacterium não Tuberculosas/complicações , Infecções por Mycobacterium não Tuberculosas/diagnóstico , Infecções por Mycobacterium não Tuberculosas/tratamento farmacológico , Artrite/diagnóstico , Artrite/etiologia
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