A5033993023- Systemic Lupus Erythematosus Research
- Rheumatoid Arthritis Research and Therapies
- Inflammasome and immune disorders
- Vasculitis and related conditions
- T-cell and B-cell Immunology
- Autoimmune and Inflammatory Disorders Research
- Eosinophilic Disorders and Syndromes
- Immune Cell Function and Interaction
- Inflammatory Myopathies and Dermatomyositis
- IgG4-Related and Inflammatory Diseases
- Atherosclerosis and Cardiovascular Diseases
- interferon and immune responses
- Systemic Sclerosis and Related Diseases
- Viral Infections and Immunology Research
- IL-33, ST2, and ILC Pathways
- Renal Diseases and Glomerulopathies
- Musculoskeletal synovial abnormalities and treatments
- Monoclonal and Polyclonal Antibodies Research
- Neuroendocrine Tumor Research Advances
- Immunodeficiency and Autoimmune Disorders
- Bone and Joint Diseases
- Sarcoidosis and Beryllium Toxicity Research
- Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis
- Cytokine Signaling Pathways and Interactions
- Urticaria and Related Conditions
Nagasaki University
2016-2025
Nagasaki University Hospital
2015-2024
Beth Israel Deaconess Medical Center
2019-2024
Harvard University
2019-2024
Education Development Center
2019
Center for Rheumatology
2015-2018
Nagasaki Medical Center
2011-2018
Japan Agency for Medical Research and Development
2018
Yale University
2018
American College of Rheumatology
2018
We investigated the relationships among M1 monocytes, M2 osteoclast (OC) differentiation ability, and clinical characteristics in patients with rheumatoid arthritis (RA).Peripheral blood mononuclear cells (PBMCs) were isolated from RA healthy donors, we then number of monocytes or by fluorescence-activated cell sorting. also obtained cultured CD14-positive PBMCs donors to investigate OC vitro.Forty 20 included. Twenty-two (55%) anticitrullinated protein antibody (ACPA) positive. The median...
Th1 and Th17 are important in the pathogenesis of autoimmune diseases they depend on glycolysis as a source energy. T cell antigen receptor signaling phosphorylates serine/threonine kinase, calcium/calmodulin-dependent protein kinase IV (CaMK4), promotes glycolysis. Based these findings we hypothesized that CaMK4 Camk4-deficient CD4+ cells treated with inhibitor had less compared their counterparts. Pull-down mass spectrometry identified pyruvate muscle isozyme (PKM), final rate-limiting...
The aim of this study was to evaluate the clinical manifestations and prevalence familial Mediterranean fever (FMF) in Japanese patients with unexplained rheumatic manifestations. We enrolled 601 or suspected FMF throughout Japan between 2009 2015. Patients were divided into three groups according Tel Hashomer criteria: sure FMF, probable non-FMF patients, including definitive diseases. Mutation detection exons 1, 2, 3, 10 gene MEFV performed by direct sequencing. A total 192 (31.9 %)...
To clarify the significance of immunometabolism in systemic lupus erythematosus (SLE), and to determine effect calcium/calmodulin-dependent protein kinase 4 (CaMK4) on T cell metabolism.Metabolomic profiling was performed using capillary electrophoresis mass spectrometry naive cells from MRL/lpr mice treated with anti-CD3/CD28 antibodies absence or presence a CaMK4 inhibitor (KN-93). The expression GLUT1 CD4+ healthy controls (n = 16), patients inactive SLE 13), active 14) examined by flow...
The precise cytokine networks in the serum of individuals with familial Mediterranean fever (FMF) that are associated its pathogenesis have been unknown. Here, we attempted to identify specific biomarkers diagnose or assess disease activity FMF patients. We measured levels 45 cytokines 75 patients and 40 age-matched controls by multisuspension array. "attack" "remission" was classified Japan College Rheumatology-certified rheumatologists according Tel Hashomer criteria. Cytokines were ranked...
Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by defective regulatory T (T reg ) cells. Here, we demonstrate that a cell–specific deletion of calcium/calmodulin-dependent protein kinase 4 (CaMK4) improves in B6. lpr lupus-prone mice and expands Mechanistically, CaMK4 phosphorylates the glycolysis rate-limiting enzyme 6-phosphofructokinase, platelet type (PFKP) promotes aerobic glycolysis, while its end product fructose-1,6-biphosphate suppresses oxidative...
The recruitment of interleukin-17 (IL-17)-producing T helper (Th17) cells to inflammatory sites has been implicated in the development organ damage and autoimmune diseases including systemic lupus erythematosus (SLE). To define mechanism calcium/calmodulin-dependent kinase IV (CaMKIV) activation Th17 cell target tissues, we performed anti-glomerular basement membrane antibody-induced glomerulonephritis (AIGN) experiments mice studied samples from patients with SLE.We induced experimental...
Polymyositis/dermatomyositis (PM/DM) is an autoimmune disease that sometimes complicated with rapidly progressive interstitial lung (RPILD). However, serum and biomarkers can predict RPILD development remain unclear.To determine potential in patients PM/DM-ILD.In total, 49 PM/DM-ILD were enrolled. We measured the levels of 41 cytokines/chemokines, ferritin anti-MDA5 antibody, compared them between (n = 23) non-RPILD 26) groups, ranked by their importance through random forest analysis. To...
A relationship between antineutrophilic cytoplasmic antibody (ANCA)-associated vasculitis (AAV) and complement has been shown, an important role in the pathogenesis of AAV. The clinical characteristics AAV with hypocomplementemia still remain unclear. We conducted observational study 81 patients (median onset age 71 years; 58% female). Using medical records, we analyzed patients' baseline variables, laboratory data, symptoms, therapeutic outcomes after treatments including episodes relapses,...
Fibroblast-like synovial cells (FLS) have multilineage differentiation potential including osteoblasts. We aimed to investigate the role of microRNAs during osteogenic rheumatoid arthritis (RA)-FLS. RA-FLS were differentiated in medium for 21 days. Osteogenic was evaluated by alkaline phosphatase (ALP) staining and Alizarin Red staining. MicroRNA (miRNA) array analysis performed differentially expressed miRNAs differentiation. Expression miR-218-5p (miR-218) determined quantitative real-time...
HLA-DRB1 alleles are major determinants of genetic predisposition to rheumatic diseases. We assessed whether DRB1 associated with susceptibility particular clinical features adult onset Still's disease (AOSD) in a Japanese population by determining the allele distributions.DRB1 genotyping 96 patients AOSD and 1,026 healthy controls was performed. Genomic DNA samples from were also genotyped for MEFV exons 1, 2, 3, 10 direct sequencing.In AOSD, we observed predisposing association DRB1*15:01...
Rationale: As the initial treatment of rapidly progressive interstitial lung disease (RPILD) with antimelanoma differentiation-associated gene 5 antibody (anti-MDA5 Ab)-positive dermatomyositis (DM) patients, a combination corticosteroids, cyclophosphamide, and calcineurin inhibitor is recommended. However, some these patients have poor prognoses despite such intensive treatment. Other more effective treatments are desired. We report case an anti-MDA5 Ab-positive DM patient who had developed...
Relapsing epiglottitis has rarely been reported, and its etiology is not well established. A 44‐year‐old previously healthy Japanese man presented with a quickly progressing choking sensation. He had experiencing refractory relapsing laryngeal edema probably acute (three episodes within 2 weeks), rash elevated pancreatic amylase. The patient required immediate intubation. After the initial extubation, he reintubation subsequent tracheostomy. Antibiotics, glucocorticoid, antihistamines were...
Objectives To evaluate the potential of clinical factors, ultrasound findings, serum autoantibodies, and cytokine chemokine profiles as predictors outcomes in rheumatoid arthritis (RA). Patients methods We included 200 patients with RA treated biological targeted synthetic disease-modifying antirheumatic drugs a prospective multicentre cohort study. Their levels multiple cytokines chemokines, autoantibodies (anti-cyclic citrullinated peptide-2 (anti-CCP2) anti-carbamylated protein...
It is not known whether autonomic neuropathy a feature of Sjögren's syndrome (SS) or it related to circulating antiganglionic acetylcholine receptor (gAChR) antibodies. The goal the present study was investigate dysfunction in patients with SS and associations between dysfunction, anti-gAChR antibodies, clinical features SS.(1) first observational tested for presence gAChR antibodies serum samples from 39 (absent information regarding symptoms) healthy volunteers. (2) In second study,...
The aim of this study was to determine the expressions Toll-like receptors (TLRs) 7-9 and type I interferon (IFN) signal in labial salivary glands (LSGs) cultured gland epithelial cells (SGECs) from primary Sjögren's syndrome (pSS) patients. We performed an immunohistochemistry analysis LSGs 11 patients with pSS as defined by American-European Consensus Group classification criteria five healthy subjects. patients' SGECs were analyzed immunofluorescence western blotting. IFN-α expression...
We sought to identify the microRNA (miRNA) profile and potential biomarkers in FMF clarify their gene targets elucidate pathogenesis of FMF.We performed an miRNA microarray using serum from patients attack remission. then examined expression miRNAs macrophages derived THP-1 cells stimulated with toll-like receptor (TLR) ligands. Macrophages transfected pre-miRNA were lipopolysaccharides (LPSs) for quantification inflammatory cytokine production. To target genes, we overexpressed a...
Objective: We investigated clinical outcomes in patients with remitting seronegative symmetrical synovitis pitting edema (RS3PE) syndrome. Methods: This is a retrospective multicenter study conducted Nagasaki, Japan. consecutively diagnosed total of 41 RS3PE syndrome between October 2003 and September 2012 evaluated their from medical records the first year follow-up. Results: Although an excellent initial response to corticosteroids was noted all patients, 34 (82.9%) were still receiving 13...
We evaluated the efficacy and safety of tofacitinib in patients with rheumatoid arthritis (RA) a real-world setting.Seventy consecutive patients, for whom was initiated between November 2013 May 2016, were enrolled. All fulfilled 2010 ACR/EULAR classification criteria RA. received 5 mg twice daily followed 24 weeks. Clinical disease activity indicated by score (DAS)28-ESR, simplified index, clinical index as well adverse events (AEs) evaluated. Statistical analysis performed to determine...
To identify potential biomarkers to distinguish adult-onset Still's disease (AOSD) from sepsis.We recruited 70 patients diagnosed with AOSD according the Yamaguchi criteria, 22 sepsis, and 118 age-matched controls. Serum levels of 40 cytokines were analyzed using multi-suspension cytokine array. We performed a cluster analysis each in sepsis groups order specific molecular networks. Further, multivariate classification (random forest analysis) logistic regression used rank by their...
We showed previously that Japanese individuals with familial Mediterranean fever (FMF) have a more atypical phenotype compared to endemic areas. The clinical differences between young-onset FMF (YOFMF), adult-onset (AOFMF), and late-onset (LOFMF) in Japan are unclear.We enrolled 395 consecutive patients. defined YOFMF, AOFMF, LOFMF as the onset of at < 20, 20-39, ≥ 40 years age, respectively. manifestations MEFV mutations patterns among these groups.Median ages were YOFMF 12.5 (n = 182),...