Yuichiro Fujieda

Yuichiro Fujieda
Hokkaido University | Hokudai · Department of Rheumatology, Endocrinology and Nephrology

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104
Publications
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Publications

Publications (104)
Article
Objectives: Systemic lupus erythematosus (SLE) is a systemic autoimmune disease characterized by multi-organ dysfunction. Neuropsychiatric SLE (NPSLE) occurs in 30~40% of lupus patients and is the most severe presentation of SLE, frequently resulting in limitation of daily life. Recent studies have shown that microglia, tissue-resident macrophages...
Article
Objective Systemic sclerosis (SSc) is associated with pulmonary vascular disease (PVD) and interstitial lung disease (ILD), making it difficult to differentiate pulmonary arterial hypertension and pulmonary hypertension (PH) due to lung diseases and/or hypoxia and to decide treatments. We aimed to predict the response to pulmonary vasodilators in p...
Article
Objectives The central nervous system disorder in systemic lupus erythematosus (SLE), called neuropsychiatric lupus (NPSLE), is one of the most severe phenotypes with various clinical symptoms, including mood disorder, psychosis and delirium as diffuse neuropsychological manifestations (dNPSLE). Although stress is one of the aggravating factors for...
Article
Background The management of rheumatoid arthritis (RA) has been transformed by the use of molecular targeted therapies. Early treatment and treat-to-target approach leads to good clinical response and remission (responders), but not in all patients. Environmental factors including diet contribute to the development, activity and severity of RA. Evi...
Preprint
Objectives Brain function controls cognition and pain perception. The dynamics of brain function also affects physiopsychological status in individuals with neuropsychiatric diseases or chronic pain, and could be evaluated by functional magnetic resonance imaging (fMRI). The brain functional connectivity is aberrant in inflammatory arthritis (IA) i...
Article
Full-text available
The objective of this study is to clarify the clinical features and risk factors of venous thromboembolism (VTE) in patients with rheumatoid arthritis (RA). We retrospectively reviewed the prevalence of VTE in RA patients who visited Hokkaido University Hospital from 2010 to 2019 and had more than 2 years of follow-up. To explore the risk to develo...
Article
Background : Brain activity is reported to be associated with individual pain susceptibility and inflammatory status, possibly contributing to disease activity assessment in inflammatory arthritis (IA) including rheumatoid arthritis (RA) and spondyloarthritis (SpA). However, what alteration of brain function associated with disease activity and the...
Article
Objective To clarify the efficacy and safety of abatacept for glandular and extraglandular involvements in Sjögren’s syndrome (SS) associated with rheumatoid arthritis (RA). Patients and methods We performed an open-label, prospective, 1-year, observational multicenter study (ROSE and ROSE II trials) for SS with RA. The primary endpoint was the re...
Article
Objectives We aimed to identify the clinical significance of anti-ganglionic nicotinic acetylcholine receptor α3 subunit (gAChRα3) antibodies (Abs) in patients with systemic lupus erythematosus (SLE). Methods This retrospective study comprised adult patients with SLE who visited our hospital from 2006 through 2019. Anti-gAChRα3 Abs were measured i...
Article
Multicentric Castleman disease–thrombocytopenia, anasarca, reticulin fibrosis of bone marrow, renal dysfunction and organomegaly (MCD‐TAFRO)—is an emergent phenotype characterized by lymphoproliferation, fluid collection, hemocytopenia and multiple organopathy. Although studies have demonstrated an aberrant blood cytokine/chemokine profile referred...
Article
Objectives: To identify the subpopulation of rheumatoid arthritis (RA) non-responders to Janus kinase inhibitors (JAKis) using cluster analysis. Methods: This retrospective study enrolled RA patients who had been treated with JAKis (tofacitinib or baricitinib) between July 2013 and September 2019 in six centres. The endpoint was set as inadequat...
Article
Background Group 1 and 3 pulmonary hypertension (PH) develop through different pathological mechanisms but have similar hemodynamic abnormalities. Systemic sclerosis (SSc) is associated with both pulmonary vascular disease (PVD) and interstitial lung disease (ILD), making it challenging to differentiate group 1 and 3 PH in those patients. A previou...
Article
Objectives: Systemic sclerosis associated pulmonary arterial hypertension (SSc-PAH) is of clinical significance owing to its poor outcome. One of the explanations for the outcome is the co-presence of left heart disease (LHD). The aim of this study is to assess LHD phenotype in patients with SSc and pulmonary hypertension (PH). Methods: This stu...
Article
Full-text available
Antiphospholipid syndrome (APS) is a systemic disorder clinically characterized by widespread thrombosis and obstetric complications associated with the persistent presence of antiphospholipid antibodies (aPLs). The persistent presence of aPLs represents a thrombotic risk in APS, which can be stratified according to the aPL profile. Thrombosis occu...
Article
Full-text available
Neuropsychiatric systemic lupus erythematosus is an autoimmune disorder characterized by an irregular ex-change between the central nervous system and the immune system, leading to the outbreak of neurologicalconditions with possible disabling effects. Although neuropsychiatric systemic lupus erythematosus is the mostcommon expression of lupus cond...
Article
Objective: Using cluster analysis, to identify the subgroup of patients with APS with the poorest prognosis and clarify the characteristics of that subgroup. Methods: This is a longitudinal retrospective cohort study of APS patients. Using clinical data and the profile of aPL, cluster analysis was performed to classify the patients into subgroup...
Article
Glucocorticoid-induced hyperglycemia (GIH) is an important complication to be managed by rheumatologists as it can affect morbidity and mortality of patients. Before administration of glucocorticoids, risk for the development of GIH should be assessed in every patient. A meta-analysis identified male gender, older age, family history of diabetes me...
Article
Objective: No evidence has shown the efficacy of Sodium Risedronate (Risedronate) for glucocorticoid-induced osteoporosis (GIO) in patients with Rheumatoid arthritis (RA). The aim of this study was to explore the effectiveness and safety of Risedronate for GIO complicated with RA. Methods: This was a six-month randomized, double-blind, placebo-cont...
Article
Full-text available
Objective This study aimed to explore the risk factors for ‘severe’ neuropsychiatric (NP) flare in patients with systemic lupus erythematosus (SLE). Methods This retrospective study comprised newly diagnosed 184 adult SLE patients who visited Hokkaido University Hospital between 2006 and 2017. In this study, severe NP flare was defined as the occu...
Article
Full-text available
Infectious disease with various presentations in systemic lupus erythematosus (SLE) often resembles lupus flare. A 37-year-old woman presented with a swollen left index finger that had not resolved, despite 7 years of immunosuppressive treatment. MRI showed rice-body formation in the flexor tendon sheath and tenosynovectomy demonstrated chronic syn...
Article
Background Oral Janus kinase inhibitors (JAKi) have dramatically altered outcomes in patients with rheumatoid arthritis (RA). However, there remains some proportion of patients who respond to inadequately JAKi treatment (JAKi-IR) [1,2]. The characteristics in RA patients associated with JAKi-IR have not been fully demonstrated. Objectives To clari...
Article
Full-text available
Systemic lupus erythematosus (SLE) is a systemic autoimmune disease characterised by diverse organ damages resulting from various autoantibodies, such as antinuclear or anti-DNA antibodies. Neuropsychiatric lupus (NPSLE) refers to the neurological and psychiatric disorders complicated with SLE and can be challenging for physicians to manage. NPSLE...
Article
Objectives Optineurin (OPTN) is an autophagy adaptor/receptor which acts as an intrinsic negative regulator of osteoclast differentiation. Receptor activator of nuclear factor‐κB ligand (RANKL) expressed by rheumatoid arthritis synovial fibroblasts (RASFs) is primarily responsible for bone erosions in RA. We aim to explore the role of OPTN in the p...
Article
Full-text available
This research aimed to study the application of deep learning to the diagnosis of rheumatoid arthritis (RA). Definite criteria or direct markers for diagnosing RA are lacking. Rheumatologists diagnose RA according to an integrated assessment based on scientific evidence and clinical experience. Our novel idea was to convert various clinical informa...
Article
IntroductionAntiresorptive agent-related osteonecrosis of the jaw (ARONJ) is a rare but serious complication in patients receiving antiresorprtive agents (AR). However, the incidence of ARONJ after tooth extraction in patients with autoimmune disease (AID) remains unclear. The present study aimed to clarify the high-risk population of ARONJ in pati...
Article
Objectives: To clarify the efficacy and safety of calcineurin inhibitors (CNI) for treating adult-onset Still's disease (AOSD). Methods: This multicentre historical cohort study enrolled the consecutive patients with AOSD according to Yamaguchi classification criteria. The endpoints were set as the time from the initiation of treatment to events...
Article
Objective: Rapidly progressive interstitial lung disease (RPILD) is a major cause of death in patients with DM. Although clinically amyopathic DM (CADM) represents risk for RPILD, the incidence rate of RPILD in patients with CADM varies widely. Whole-body (WB) MRI can reveal involvement of systemic muscle and myofascia. The objective of this study...
Article
Objective The objective of this study was to clarify the efficacy and safety of factor Xa inhibitors for antiphospholipid syndrome patients in real world utilization. Methods This is a retrospective cohort study comprised of all consecutive patients with antiphospholipid syndrome in our department over a period of 28 years. Patients treated with f...
Article
Objectives We aimed to evaluate the obstetric complications and the risk factors for these events in pregnant women with rheumatic diseases (RDs). Methods A single-center retrospective study of women with RDs at Hokkaido University Hospital between 2007 and 2016 was conducted. Clinical features and maternal and fetal outcomes were retrospectively...
Article
We aimed to investigate the involvement of macroautophagy/autophagy in autoimmunity in rheumatoid arthritis (RA) through citrullination of VIM (vimentin) and its interaction with MHC class II in synovial fibroblasts (SFs). The cell surface expression of MHC class II and B7 costimulatory molecules on SFs was analyzed by flow cytometry after treatmen...
Article
Gout, which is characterized by the deposition of monosodium urate monohydrate (MSU) in the synovial fluid and other tissues, is the most common form of inflammatory arthritis. Unlike the easily recognized acute and monoarticular gouty arthritis, advanced gout induces multiple finger joint disorders and may sometimes mimic rheumatoid arthritis (RA)...
Article
Full-text available
Objectives: Pulmonary hypertension (PH) in patients with CTD is a heterogeneous condition affected by left heart disease, chronic lung disease and thromboembolism as well as pulmonary vascular disease. Recent studies using cardiac magnetic resonance (CMR) have shown that right ventricular dysfunction is predictive for mortality in patients with PH...
Article
Early intervention in pulmonary arterial hypertension associated with systemic sclerosis (SSc) may improve its prognosis. We aimed to establish an algorithm to detect mean pulmonary artery pressure (mPAP) > 20 mmHg using non-invasive examinations in SSc patients by modifying the DETECT algorithm. This study included SSc patients who underwent right...
Article
Adynamic bone disease (ABD) in hemodialysis (HD) patients is characterized by skeletal resistance to parathyroid hormone (PTH) or suppression of PTH release, leading to a down‐regulated bone turnover and bone fracture. Hence, we examined the efficacy of weekly teriparatide for HD patients with low PTH indicating ABD without a history of parathyroid...
Article
Objective: Warfarin is regarded as the standard treatment for preventing thrombotic events in APS, but the recurrence rate is still high. Dual antiplatelet therapy (DAPT) has been shown to be effective for the prevention of acute coronary syndrome or stroke. The objective of this study was to evaluate the efficacy of DAPT for the prevention of thr...
Conference Paper
Background Adult-onset Still’s disease (AOSD) is a systemic inflammatory disorder generally responsive to corticosteroid (CS) therapy, whereas cases not responding CS monotherapy are frequently found in clinical practice. In such cases, methotrexate and/or biologics including TNF-α, IL-1, or IL-6 inhibitors are used [1]. However, further treatment...
Conference Paper
Background Rapidly progressive interstitial lung disease (RPILD) is a major cause of death in patients with dermatomyositis (DM). Early diagnosis and aggressive immunosuppressive therapy are required in RPILD to improve the prognosis. Clinically amyopathic dermatomyositis (CADM) and anti-melanoma differentiation-associated gene 5 antibody are known...
Article
Objective: Idiopathic osteonecrosis of the femoral head (ION) is a common complication of SLE associated with CS therapy. Although the pathogenesis of ION involves local bone ischaemia favoured by thrombophilia, the involvement of aPL in lupus ION remains to be elucidated. We have previously reported the aPL score (aPL-S) as a quantitative marker...
Article
Recurrent pregnancy loss (RPL) is often considered idiopathic, however excessive complement activation has been observed in pregnancy related manifestations. Anti-C1q antibodies (anti-C1q) are associated with the activation of complement pathway in lupus patients, while it remains unclear in RPL. Firstly, we showed that both the prevalence and titr...
Article
Antibodies against phosphatidylserine–prothrombin complexes (PS–PT) are one type of antiphospholipid antibody that is responsible for lupus anticoagulant activity. Anti-PS–PT antibodies are not currently included in the classification criteria for antiphospholipid syndrome (APS), but should they replace lupus anticoagulant testing to improve the di...
Article
Full-text available
Rationale: Neutrophil extracellular traps (NETs) are immune defence systems that release extracellular chromatin and myeloid granules including myeloperoxidase (MPO) to kill pathogens. An experimental animal study recently demonstrated that disordered NETs induced by propylthiouracil (PTU) could contribute to the production of MPO anti-neutrophil...
Article
Background/Objective Antiphospholipid antibodies (aPL) are pathogenic autoantibodies in antiphospholipid syndrome (APS). This study aimed to clarify the mechanism of aPL production. Methods T cell and B cell subsets were evaluated in peripheral blood mononuclear cells (PBMCs) of 26 primary APS (PAPS), 19 systemic lupus erythematosus‐associated APS...
Article
Objectives: Thrombocytopenia is frequently observed in antiphospholipid antibody (aPL) carriers. Due to the paradoxical risks of thrombosis and hemorrhage, the management of aPL-associated thrombocytopenia (APAT) is often deductive. We aimed to investigate the efficacy and safety of therapeutic approaches for APAT through a systematic review. Metho...
Article
Full-text available
Rationale: An association between inflammatory myopathy and malignancy has been recognized particularly in patients positive for anti-transcription intermediary factor 1γ (TIF1γ) antibody. We report a case of anti-TIF1γ antibody positive dermatomyositis (DM) associated with thymic carcinoma which radiographically mimicked benign tumor. Patient co...
Article
Full-text available
Cognitive impairment occurs in 40–90% of patients with systemic lupus erythematosus (SLE), which is characterized by autoantibodies to nuclear antigens, especially DNA. We discovered that a subset of anti-DNA antibodies, termed DNRAbs, cross reacts with the N-methyl- d -aspartate receptor (NMDAR) and enhances NMDAR signaling. In patients, DNRAb pre...
Article
Background Anti‐DNA/N‐methyl‐D‐aspartate receptor 2 (NR2) antibodies (anti‐DNA/NR2 antibodies) are a subset of anti‐DNA autoantibodies that cross‐react with the extracellular domain of the GluN2A/GluN2B subunits of NR2. These antibodies induce apoptosis of hippocampus neurons and psychiatric disorder in mice and humans. Neuropsychiatric system lupu...
Article
Objectives Rheumatoid arthritis (RA) is an autoimmune polyarthritis, in which fibroblast-like synoviocytes (FLS) play a key role in cartilage and bone destruction through tumour-like proliferation and invasiveness. Considering still unsatisfactory remission rate in RA even under treatment with biological disease-modifying antirheumatic drugs, novel...
Article
Objective T cells from SLE patients have reduced protein levels of RasGRP1, a guanine nucleotide exchange factor for Ras, and increased transcript of alternatively spliced (AS) forms lacking exon 11. Serine/arginine‐rich splicing factor 1 (SRSF1) binds pre‐mRNA to regulate AS forms of several genes, including CD3ζ in SLE T cells. This study aimed t...
Conference Paper
Full-text available
Background Subclinical and overt lung diseases associated with rheumatoid arthritis (RA-LD) are present in 30%–50% of the patients. Early and effective intervention improved joint prognosis in RA. By contrast, lung complications are still the primary contributors to premature deaths in patients with RA. Lung complication in RA can be due to a varie...
Conference Paper
Background Antiphospholipid antibodies (aPL) as pathogenic autoantibodies in systemic lupus erythematosus (SLE) and antiphospholipid syndrome (APS) are supported by a number of clinical, ex vivo and animal studies. Nevertheless, aPL are not eliminated by corticosteroid administration or immunosuppression. Novel therapy targeting aPL production is c...
Conference Paper
Background Adult-onset Still’s disease (AOSD) is a systemic inflammatory disorder generally responsive to corticosteroid therapy, whereas refractory AOSD is often encountered that not controlled by corticosteroid monotherapy. In such cases, methotrexate and biologics including TNF-α, IL-1, or IL-6 inhibitors are used.¹ However, more treatment optio...
Article
Introduction: Although complement activation has been proposed as a possible thrombophilic mechanism in antiphospholipid syndrome (APS), the origin of complement activation in APS remains unclear. Here, we focused on complement regulatory factors (CRF), which control the complement system to prevent damage to host tissue. We evaluated the function...
Article
Objectives: To elucidate the efficacy and safety of autologous haematopoietic stem cell transplantation (HSCT) for Japanese patients with systemic sclerosis (SSc). Methods: A phase II clinical trial included SSc patients diagnosed within the last three years having at least one of the following clinical features: diffuse skin sclerosis with modi...
Article
Objectives: Presepsin (PSEP: soluble CD14 subtype) is produced from bacteria-stimulated monocytes or neutrophils, thus recognized as a biomarker of sepsis. Aberrant functions in monocyte or neutrophils are increasingly recognized in systemic lupus erythematosus (SLE). We investigated whether plasma PSEP reflects disease activity in patients with SL...
Article
Objectives: The aim of this study was to clarify the consequences of Mx1, one of the IFN-inducible proteins, in the peripheral blood as well as in renal tissues in patients with systemic lupus erythematosus (SLE). Patients and methods: Mx1 protein concentrations in (PBMCs) from 18 SLE patients mostly in their stable disease status, 11 IgA nephropat...
Article
Objective: DWEYS-IgG cross-reactive with DNA and the N-methyl-D-aspartate receptor subunits GluN2A/GluN2B has been associated with neuropsychiatric systemic lupus erythematosus (NPSLE). DWEYS-IgG has not been investigated in demyelinating NPSLE (dNPSLE) or in another demyelinating disorder, Neuromyelitis Optica Spectrum Disorder (NMOSD), which is...
Article
Full-text available
We investigated the serum haptoglobin levels in patients with pulmonary arterial hypertension (PAH) based on the hypothesis that haptoglobin levels would reflect subclinical hemolysis due to microangiopathy in pulmonary arterioles. This cross-sectional study included 3 groups of patients attending Hokkaido University Hospital: PAH, chronic thromboe...
Article
Objective: The aim of this study was to assess the value of a combination of anti-beta2-glycoprotein I domain I antibodies (aDI) and phosphatidylserine-dependent antiprothrombin antibodies (aPS/PT) tests for the diagnosis of antiphospholipid syndrome (APS). Methods: This cross-sectional study involved a cohort of the patients who visited our cli...
Article
Background: Thrombocytopenia is a non-criteria clinical manifestation of antiphospholipid syndrome (APS). However, it remains to be elucidated whether thrombocytopenia increases thrombotic risk in antiphospholipid antibody (aPL) carriers. Objectives: To investigate the impact of platelet count in terms of predicting thrombotic events in aPL carr...
Conference Paper
Background In recurrent pregnancy loss (RPL), the pathogenesis of the majority of cases remains to be explained. Antiphospholipid, syndrome (APS) is one of the disorder responsible for causing RPL and its overwhelmed complement activation recognized as a major pathogenic mechanism. Autoantibodies against complement component 1q subcomponent (aC1q)...
Conference Paper
Background Pulmonary arterial hypertension (PAH) is of great clinical significance as a life-threatening complication of connective tissue diseases (CTD). Pulmonary artery thrombotic microangiopathy (PATM) is an important pathophysiology of PAH. The concept of PATM refers to localized thrombotic microangiopathy to be defined histologically and shou...
Conference Paper
Background Systemic lupus erythematosus (SLE) patients are prone to develop idiopathic osteonecrosis (ION) compared to other connective tissue disease patients or healthy subjects. ION has been shown to occur as a result of ischemia, however, the involvement of antiphospholipid antibodies (aPL) in its pathophysiology remains to be elucidated. In th...
Conference Paper
Background and Aims Our group introduced a quantitative marker of antiphospholipid antibodies (aPL) ‘‘antiphospholipid score (aPL-S)’’, which well reflected the risk of developing thrombosis (Otomo K, et al. Arthritis Rheum 2012). Idiopathic osteonecrosis (ION) has been shown to occur as a result of ischemia, however, the involvement of aPL in its...
Conference Paper
Neuropsychiatric lupus manifestations, especially the common disorders of mood and cognition, can be mediated by cytokines or by antibodies. In particular, a subset of anti-DNA antibodies has been shown to bind the N-methyl d-aspartate receptor. The antibodies preferentially bind the active configuration of the receptor, augmenting the effects of l...