Abstract:
OBJECTIVE:Neutrophil extracellular traps (NETs) are peculiar structures composed of the externalized chromatin with intracellular proteins and formed by activated neutrophils in a reactive oxygen species (ROS)-dependent manner. Aberrant NETs are considered to be autoantigens for anti-neutrophil cytoplasmic antibodies (ANCAs) underling the development of microscopic polyangiitis (MPA). However, little is known regarding the therapeutic efficacy of in vivo inhibition of NET formation (NETosis) on MPA pathogenesis. This study determines whether reducing NETosis prevents ANCA production and improves characteristic involvement. METHODS:A mouse model of MPA induced by administering a novel extract from Candida albicans was devised. By applying this method to mice lacking phosphoinositide 3-kinase gamma (PI3K-gamma), which is indispensable for ROS production in neutrophils, we investigated the levels of in vivo NETs, ANCA titers and histological damage. RESULTS:Our model exhibited accumulation of NETs in vivo, elevation of ANCA titers and characteristic pathologies mimicking human MPA, including small-vessel vasculitis and crescentic glomerulonephritis. Strikingly, these abnormalities were reduced by genetically and/or pharmacologically blocking PI3K-gamma. Moreover, a pharmacological PI3K-gamma blockade decreased the levels of human NETs. CONCLUSION:Our results suggest that in vivo inhibition of NETosis by blocking PI3K-gamma could be a promising therapeutic strategy for the pathogenesis of MPA.
journal_name
Mod Rheumatoljournal_title
Modern rheumatologyauthors
Kimura H,Matsuyama Y,Araki S,Koizumi A,Kariya Y,Takasuga S,Eguchi S,Nakanishi H,Sasaki J,Sasaki Tdoi
10.1080/14397595.2017.1367116subject
Has Abstractpub_date
2018-05-01 00:00:00pages
530-541issue
3eissn
1439-7595issn
1439-7609journal_volume
28pub_type
杂志文章abstract::We investigated the expression and localization of heme oxygenase-1 (HO-1) in synovial fluid and synovial tissue, and examined the stimulation of HO-1 production in rheumatoid synovial fibroblasts (RASFs). Synovial fluid samples were obtained from knee joints of 20 rheumatoid arthritis (RA) and 20 osteoarthritis (OA) ...
journal_title:Modern rheumatology
pub_type: 杂志文章
doi:10.1007/s10165-010-0372-9
更新日期:2011-04-01 00:00:00
abstract:OBJECTIVE:To assess the utilities of ultrasonography (US) and low-field magnetic resonance imaging (compacTscan, cMRI) in the diagnosis of subclinical synovitis of hand joints of patients with rheumatoid arthritis (RA). METHODS:A total of 1,540 joints of 77 RA patients were examined clinically, using US, using cMRI, a...
journal_title:Modern rheumatology
pub_type: 杂志文章
doi:10.3109/14397595.2013.854050
更新日期:2014-01-01 00:00:00
abstract:OBJECTIVES:To understand the status of mizoribine use in patients with lupus nephritis (LN) and to collect safety- and efficacy-related data on 2-year treatment with mizoribine. METHODS:A continuous survey was conducted between March 2010 and July 2015. RESULTS:The analysis set included 559 patients (mean age 39.5 ye...
journal_title:Modern rheumatology
pub_type: 杂志文章
doi:10.1080/14397595.2017.1349573
更新日期:2018-01-01 00:00:00
abstract::We performed this study to investigate the differences in radiological and laboratory findings between systemic juvenile idiopathic arthritis (s-JIA) and polyarthritis (p-JIA). Twenty-two patients with s-JIA and 18 with p-JIA were enrolled. Their laboratory findings and radiographs were examined retrospectively. Plain...
journal_title:Modern rheumatology
pub_type: 杂志文章
doi:10.1007/s10165-011-0540-6
更新日期:2012-08-01 00:00:00
abstract::A 68-year-old Japanese male presented with atrophic erythematous white lesions with peripheral dark reddish rims on his back. Multiple ulcers were detected from his stomach to his large intestine using endoscopy. Although the patient was given high doses of a steroid, aspirin, dipyridamole, and intravenous immunoglobu...
journal_title:Modern rheumatology
pub_type: 杂志文章
doi:10.3109/14397595.2013.874761
更新日期:2015-05-01 00:00:00
abstract::Sarcoidosis is a multisystem disease related to helper T cell responses. We recently experienced the case of a 57-year-old woman with sarcoidosis complicated by crescentic glomerulonephritis with low levels of myeloperoxidase-antineutrophil cytoplasmic antibody. We herein describe the details of her clinical course an...
journal_title:Modern rheumatology
pub_type: 杂志文章
doi:10.1007/s10165-012-0614-0
更新日期:2013-01-01 00:00:00
abstract::Objective: This study aimed to clarify whether plasma acrolein level actually increases in rheumatoid arthritis (RA) patients, and to elucidate whether any relationship exists between the levels and the RA background variables.Methods: Plasma levels of protein-conjugated acrolein (PC-Acro) in 84 patients (RA group) an...
journal_title:Modern rheumatology
pub_type: 杂志文章
doi:10.1080/14397595.2020.1775921
更新日期:2020-06-16 00:00:00
abstract:OBJECTIVE:The international classification criteria (CC) for definite antiphospholipid syndrome (APS) recommend confirmation of the sustained presence, for at least 12 weeks, of both lupus anticoagulant (LA), as determined by aPTT and RVVT, and anti β2glycoprotein I (β2GPI) or anticardiolipin (aCL) IgG and/or IgM. Howe...
journal_title:Modern rheumatology
pub_type: 杂志文章
doi:10.3109/14397595.2015.1023978
更新日期:2015-01-01 00:00:00
abstract::We evaluated the prevalence of Helicobacter pylori infection and the association of H. pylori infection and/or nonsteroidal anti-inflammatory drug (NSAID) use with upper gastrointestinal (UGI) ulcers in a cohort of Japanese patients with rheumatoid arthritis (RA). Using the clinical database of the cohort of RA patien...
journal_title:Modern rheumatology
pub_type: 杂志文章
doi:10.1007/s10165-005-0419-5
更新日期:2005-01-01 00:00:00
abstract::Blau syndrome/early-onset sarcoidosis (Blau/EOS) is an autoinflammatory disease characterized by granulomatous arthritis, uveitis, and skin rash. It has been shown that gain-of-function NOD2 mutations cause Blau/EOS. In this paper, we describe a patient with a gain-of-function NOD2 mutation who developed infantile Tak...
journal_title:Modern rheumatology
pub_type: 杂志文章
doi:10.1007/s10165-012-0720-z
更新日期:2013-07-01 00:00:00
abstract::The association of either thrombotic thrombocytopenic purpura (TTP) or crescentic glomerulonephritis with Sjögren's syndrome is rare. We report a case of TTP appearing after the diagnosis of SjOgren's syndrome with crescentic glomerulonephritis and membranous nephropathy. Circulating immune complex was detected, and i...
journal_title:Modern rheumatology
pub_type: 杂志文章
doi:10.1007/s10165-004-0287-4
更新日期:2004-01-01 00:00:00
abstract::Abstract The human major histocompatibility complex (MHC) class I gene HLA-B27 bears a striking association with ankylosing spondylitis and related spondyloarthropathies. This association transcends all ethnic and geographical boundaries. The primary function of HLA-B27 as an MHC class I protein is to form a complex w...
journal_title:Modern rheumatology
pub_type: 杂志文章
doi:10.3109/s10165-001-8056-0
更新日期:2001-12-01 00:00:00
abstract:OBJECTIVES:To evaluate joint inflammation using 3-T MRI in rheumatoid arthritis (RA) patients treated with conventional disease modifying anti-rheumatic drugs (cDMARDs) as compared to inhibitors for tumor necrosis factor α (TNFi) over 12 months. METHODS:Prospective epidemiologic clinical pilot study using the RA MRI s...
journal_title:Modern rheumatology
pub_type: 杂志文章
doi:10.1080/14397595.2018.1467525
更新日期:2019-05-01 00:00:00
abstract:: ...
journal_title:Modern rheumatology
pub_type: 杂志文章
doi:10.1007/s10165-013-0870-7
更新日期:2013-04-04 00:00:00
abstract::Abstract We report a rare case of a 17-year-old female with overlap syndrome (systemic lupus erythematosus and systemic sclerosis) who developed severe abdominal pain and bloody diarrhea accompanied by central nervous system lupus. Colonoscopy revealed multiple irregular and linear ulcers throughout the colon, which w...
journal_title:Modern rheumatology
pub_type: 杂志文章
doi:10.3109/s10165-003-0243-8
更新日期:2003-12-01 00:00:00
abstract::Here, we report the case of a 69-year-old man with limited granulomatosis with polyangiitis (GPA; formerly Wegener's granulomatosis) who developed papillary thyroid cancer, adenocarcinoma of the stomach, and myelodysplastic syndrome following glucocorticoid treatment. This is the first report to present multiple malig...
journal_title:Modern rheumatology
pub_type: 杂志文章
doi:10.3109/14397595.2014.891494
更新日期:2016-01-01 00:00:00
abstract:OBJECTIVES:To assess the influence of golimumab dosage and disease activity on joint destruction in patients with active rheumatoid arthritis (RA) in the GO-FORTH study. METHODS:Efficacy was compared among groups given basal methotrexate plus placebo, golimumab (50 mg), or golimumab (100 mg) with stratification by hig...
journal_title:Modern rheumatology
pub_type: 杂志文章,随机对照试验
doi:10.3109/14397595.2015.1086041
更新日期:2016-01-01 00:00:00
abstract::The aim of this study was to evaluate the incidence of morphologic and functional cardiac abnormalities in patients with systemic lupus erythematosus (SLE) and to correlate the findings with levels of anti-Ro/SS-A, anti-La/SS-B, and anti-cardiolipin antibody (aCL). Sixty-two patients with SLE were enrolled in this stu...
journal_title:Modern rheumatology
pub_type: 杂志文章
doi:10.1007/s10165-004-0277-6
更新日期:2004-01-01 00:00:00
abstract:OBJECTIVES:Psoriasis is a chronic autoimmune disease involving a complex network of cytokines such as interleukin (IL)-6. We tested the hypothesis that serum IL-6 level is a useful indicator of disease activity and predicts the treatment response to biologics in patients with psoriasis. METHODS:We analyzed 113 psorias...
journal_title:Modern rheumatology
pub_type: 杂志文章
doi:10.3109/14397595.2016.1174328
更新日期:2017-01-01 00:00:00
abstract::Abstract An accumulating body of evidence shows that gene therapy can be successfully used to treat animal models of arthritis. Based on this success, a clinical trial of gene therapy for rheumatoid arthritis has been initiated. We review the methods and genes used for the previous gene transfer experiments, including...
journal_title:Modern rheumatology
pub_type: 杂志文章
doi:10.3109/s101650050003
更新日期:2000-06-01 00:00:00
abstract::We performed total hip arthroplasty using the non-cement impaction auto-bone-grafting method with the resected femoral head for acetabular protrusion that is not combined with the destruction of acetabular rim or dysplasia of the hip joint. Ten patients (eight women and two men) with rheumatoid arthritis who showed ac...
journal_title:Modern rheumatology
pub_type: 临床试验,杂志文章
doi:10.1007/s10165-007-0571-1
更新日期:2007-01-01 00:00:00
abstract::We investigated the clinical efficacy and safety of tocilizumab (a humanized anti-IL-6 receptor antibody) monotherapy in active rheumatoid arthritis (RA) patients with an inadequate response to low dose methotrexate (MTX). In a multicenter, double-blind, randomized, controlled trial, 125 patients were allocated to rec...
journal_title:Modern rheumatology
pub_type: 杂志文章,多中心研究,随机对照试验
doi:10.1007/s10165-008-0125-1
更新日期:2009-01-01 00:00:00
abstract::'Immunoglobulin G4 (IgG4)-related disease' is a new clinical concept of multi-organ diseases, with Mikulicz's disease (MD) being a clinical phenotype of IgG4-related disease. To clarify the clinical characteristics of respiratory involvement associated with IgG4-related MD, we retrospectively assessed 25 patients with...
journal_title:Modern rheumatology
pub_type: 杂志文章
doi:10.1007/s10165-011-0504-x
更新日期:2012-02-01 00:00:00
abstract::Objectives: To assess the effects of belimumab on disease activity across multiple organ domains in Japanese patients from the Phase 3 randomized, double-blind, North-East Asia study, BEL113750 (NCT01345253).Methods: Patients, aged ≥18 years, with American College of Rheumatology-defined systemic lupus erythematosus (...
journal_title:Modern rheumatology
pub_type: 杂志文章,随机对照试验
doi:10.1080/14397595.2019.1630897
更新日期:2020-03-01 00:00:00
abstract::Objectives: Delayed wound healing is one of the most common complications following forefoot surgery in patients with rheumatoid arthritis. We aimed to identify the risk factors for delayed wound healing following rheumatoid forefoot surgery.Methods: Consecutive patients who underwent primary rheumatoid forefoot surge...
journal_title:Modern rheumatology
pub_type: 杂志文章
doi:10.1080/14397595.2020.1775960
更新日期:2020-06-16 00:00:00
abstract::The aim of our study was to determine the spectrum of the 12 most common familial Mediterranean fever gene (MEFV) mutations in Iranian patients with heterogeneous ethnicity, using the familial Mediterranean fever (FMF) strip assay test. A total of 36 patients were diagnosed according to established clinical criteria. ...
journal_title:Modern rheumatology
pub_type: 杂志文章
doi:10.1007/s10165-010-0317-3
更新日期:2010-12-01 00:00:00
abstract:OBJECTIVES:To assess the efficacy of tocilizumab for preventing damage to the joints of systemic juvenile idiopathic arthritis (sJIA) patients, we examined serial radiographs of the hands and large weight-bearing joints of these patients before and after treatment with this agent. METHODS:Nine patients with sJIA recei...
journal_title:Modern rheumatology
pub_type: 杂志文章
doi:10.1007/s10165-012-0711-0
更新日期:2013-07-01 00:00:00
abstract:OBJECTIVE:The prediction of hip osteoarthritis (OA) progression is still a difficult issue. We have adopted (18)F-fluoride positron emission tomography (PET) for the evaluation of hip osteoarthritis, and investigated the prediction utility of (18)F-fluoride PET for both pain worsening and OA progression using a logisti...
journal_title:Modern rheumatology
pub_type: 杂志文章
doi:10.3109/14397595.2015.1045257
更新日期:2015-01-01 00:00:00
abstract::Peripheral neuropathies should be recognized as the adverse effects of biological agents, especially anti-TNF agents. However, no solid clinical databases for biological agent-associated peripheral neuropathies (BAPN) have been established in Japan. Here we report two cases of peripheral neuropathy associated with ant...
journal_title:Modern rheumatology
pub_type: 杂志文章
doi:10.3109/14397595.2013.859770
更新日期:2016-01-01 00:00:00
abstract::Objectives: Overactive bladder (OAB) is a clinical diagnosis defined with the presence of urinary urgency, usually accompanied by frequency and nocturia, with or without urgency urinary incontinence. Objective was to evaluate the demographic and clinical characteristics of Japanese systemic sclerosis (SSc) patients wi...
journal_title:Modern rheumatology
pub_type: 杂志文章
doi:10.1080/14397595.2019.1589913
更新日期:2020-03-01 00:00:00