Michihito Kono

Michihito Kono
Hokkaido University | Hokudai · Department of Rheumatology, Endocrinology and Nephrology

MD, PhD

About

83
Publications
4,992
Reads
How we measure 'reads'
A 'read' is counted each time someone views a publication summary (such as the title, abstract, and list of authors), clicks on a figure, or views or downloads the full-text. Learn more
699
Citations

Publications

Publications (83)
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...
Article
Background Systemic lupus erythematosus (SLE) often affects women in their childbearing years, and pregnancy may affect SLE disease activity during pregnancy and post-partum (1,2). Limited data assessing the likelihood and characteristics of SLE activity in an extended time period post-partum which may be relevant as patients may wish further pregn...
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
Aberrant IL-17A expression together with reduced IL-2 production by effector CD4+ T cells contributes to the pathogenesis of systemic lupus erythematosus (SLE). Here, we report that Sirtuin 2 (SIRT2), a member of the family of NAD+-dependent histone deacetylases, suppresses IL-2 production by CD4+ T cells while promoting their differentiation into...
Article
Background: Sjögren's syndrome is a chronic autoimmune disorder that predominantly affects exocrine organs. It is characterized by an organ-specific infiltration of lymphocytes. The involvement of the major cerebral arteries in Sjögren's syndrome has rarely been reported. A recent study reported a case of successful extracranial‒intracranial (EC‒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
Objective: Glutaminase (GLS) isoenzymes GLS1 and GLS2 catalyze the first step of glutaminolysis. GLS1 is requisite for Th17 differentiation and its inhibition suppresses autoimmune disease in animals but the function of GLS2 is not known. The aim of this study was to investigate the role of GLS2 in CD4+ T cell function and systemic lupus erythemat...
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
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
The a disintegrin and metalloproteinase (ADAM) family of proteinases alter the extracellular environment and are involved in the development of T cells and autoimmunity. The role of ADAM family members in Th17 cell differentiation is unknown. We identified ADAM9 to be specifically expressed and to promote Th17 differentiation. Mechanistically, we f...
Article
Full-text available
T cell metabolism is central to cell proliferation, survival, differentiation, and aberrations have been linked to the pathophysiology of systemic autoimmune diseases. Besides glycolysis and fatty acid oxidation/synthesis, amino acid metabolism is also crucial in T cell metabolism. It appears that each T cell subset favors a unique metabolic proces...
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
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
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
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
Protein phosphatase 2A (PP2A), a serine/threonine phosphatase, has been shown to control T cell function. We found that in vitro-activated B cells and B cells from various lupus-prone mice and patients with systemic lupus erythematosus display increased PP2A activity. To understand the contribution of PP2A to B cell function, we generated a Cd19Cre...
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
Full-text available
Abnormal T cell responses are central to the development of autoimmunity and organ damage in systemic lupus erythematosus. Following stimulation, naïve T cells undergo rapid proliferation, differentiation and cytokine production. Since the initial report, approximately two decades ago, that engagement of CD28 enhances glycolysis but PD-1 and CTLA-4...
Article
Purpose of review: Th1, Th17, and Treg cells play distinct roles in autoimmune diseases, including systemic lupus erythematosus, multiple sclerosis, and rheumatoid arthritis. During the last 5 years we have learned that T-cell metabolism affects cell survival, differentiation and fate of T cells. Recent findings: We highlight recent studies whic...
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
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
Objective: Glutaminase 1 (Gls1) is the first enzyme in glutaminolysis. The selective Gls1 inhibitor Bis-2-(5-phenylacetamido-1,3,4-thiadiazol-2-yl)ethyl sulfide (BPTES) suppresses Th17 development and ameliorates experimental autoimmune encephalomyelitis (EAE). However, whether inhibition of glutaminolysis is beneficial for the treatment of system...
Article
Th1 and Th17 are important in the pathogenesis of autoimmune diseases and they depend on glycolysis as a source of energy. T cell antigen receptor signaling phosphorylates a serine/threonine kinase, calcium/calmodulin-dependent protein kinase IV (CaMK4), and promotes glycolysis. Based on these findings we hypothesized that CaMK4 promotes glycolysis...
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
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
Th17 cells favor glycolytic metabolism, and pyruvate dehydrogenase (PDH) is the key bifurcation enzyme, which in its active dephosphorylated form advances the oxidative phosphorylation from glycolytic pathway. The transcriptional factor, inducible cAMP early repressor/cAMP response element modulator (ICER/CREM), has been shown to be induced in Th17...
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
Full-text available
Podocyte malfunction occurs in autoimmune and nonautoimmune kidney disease. Calcium signaling is essential for podocyte injury, but the role of Ca2+/calmodulin-dependent kinase (CaMK) signaling in podocytes has not been fully explored. We report that podocytes from patients with lupus nephritis and focal segmental glomerulosclerosis and lupus-prone...
Article
Objective SLAMF1 homophilic interactions promote immunoglobulin production and T cell‐B cell (T‐B) cross‐talk. SLAMF1 is overexpressed on T and B cells in patients with SLE. We conducted studies to determine the role of SLAMF1 monoclonal antibody in modulating T‐B cell interaction and B cell activation. Materials Anti‐IgM pre‐stimulated naïve or t...
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...
Article
Background: Synovitis, which is a hallmark of rheumatoid arthritis (RA), needs to be precisely quantified to determine the treatment plan. Time-intensity curve (TIC) shape analysis is an objective assessment method for characterizing the pixels as artery, inflamed synovium, or other tissues using dynamic contrast-enhanced MRI (DCE-MRI). Purpose/h...
Article
Full-text available
Glutaminolysis is a well-known source of energy for effector T cells but its contribution to each T cell subset and the mechanisms which are responsible for the control of involved metabolic enzymes are not fully understood. We report that Th17 but not Th1, Th2, or Treg cell induction in vitro depends on glutaminolysis and the up-regulation of glut...
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...
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...
Article
Full-text available
RATIONALE: Palisaded neutrophilic and granulomatous dermatitis (PNGD) is a benign, inflammatory dermatosis with distinct histopathological features often observed in patients with systemic diseases. There were no reports of PNGD without underlying systemic diseases as an underlying cause of hypercalcemia. Herein, we report a case of a 62-year-old m...
Conference Paper
Background and aims Ras activation as well as MAP kinase (MAPK) phosphorylation is known in the synovial tissues from patients with rheumatoid arthritis (RA). RasGRP4 is a guanine nucleotide exchange factor for small GTPase Ras and is expressed predominantly in the mast cells, monocytes and neutrophils. We previously identified ectopic expression o...
Article
Objectives: To evaluate the scoring of whole-body magnetic resonance imaging (WBMRI) for efficacy assessment in rheumatoid arthritis (RA) patients receiving biological disease-modifying anti-rheumatic drugs (bDMARDs). Methods: Thirty consecutive RA patients receiving bDMARDs were included in this retrospective study. Contrast WBMRI was performed be...
Article
Background Despite the advantages of ultrasound (US) in the management of rheumatoid arthritis (RA) patients, power Doppler (PD) US may be highly dependent on the type of US machine used. Purpose To present a method to calibrate the PD signal of two models of US machines by use of a flow phantom and finger joints of patients with RA. Material and...
Article
Full-text available
Valosin containing protein (p97) is a chaperone implicated in a large number of biological processes including endoplasmic reticulum (ER)-associated protein degradation and autophagy. Silencing of p97 in rheumatoid arthritis (RA) synovial fibroblasts (RASFs) increased the amount of polyubiquitinated proteins, whereas silencing of its interaction pa...
Article
Full-text available
Inducible cAMP early repressor (ICER) has been described as a transcriptional repressor isoform of the cAMP response element modulator (CREM). Here we report that ICER is predominantly expressed in Th17 cells through the IL-6-STAT3 pathway and binds to the Il17a promoter, where it facilitates the accumulation of the canonical enhancer RORγt. In vit...
Data
Full-text available
Supplementary Figures 1-5 and Supplementary Tables 1-2
Article
Objectives: Pulmonary arterial hypertension (PAH) associated with systemic sclerosis (SSc) has a poor prognosis compared to PAH associated with other connective tissue diseases (CTD). The objective of this study was to examine the difference in hemodynamic state between SSc-PAH and other CTD-PAH by performing cardiac magnetic resonance (CMR) imagi...
Article
Full-text available
Signaling lymphocytic activation molecule family 3 (SLAMF3/Ly9) is a coregulatory molecule implicated in T-cell activation and differentiation. Systemic lupus erythematosus (SLE) is characterized by aberrant T-cell activation and compromised IL-2 production, leading to abnormal regulatory T-cell (Treg) development/function. Here we show that SLAMF3...
Article
Treatment of organ involvements accompanied by systemic autoimmune diseases is still challenging for clinicians, reminding the existence of unmet needs. Among them, lupus nephritis (LN), neuropsychiatric lupus, interstitial lung diseases (ILD) complicated with polymyositis/dermatomyositis (PM/DM) or systemic sclerosis (SSc) are the most severe cond...
Article
Full-text available
We examined the capability of a gray-scale arterial spin labeling blood flow pattern variation (BFPV) map with two different post labeling delay (PLD) times to discriminate pannus in patients with rheumatoid arthritis (RA) at 3T. There was a statistically significant difference in the BFPV values between artery, pannus, and surrounding tissue. Furt...
Article
Objectives: To improve on the reproducibility and sensitivity of the assessment of rheumatoid arthritis (RA) patients, two semi-automated measurement methods of the area of enhancing pannus (AEP), based on thresholding (AEP_THRES) and pixel-by-pixel time-intensity curve analysis (AEP_TIC), were evaluated as an alternative for the gold standard man...
Article
Objective: Phosphatidylserine-dependent, also called aPS-PT, recognizes the phosphatidylserine-prothrombin complex, which is associated with APS. We have previously reported that aPS-PT induces tissue factor (TF) expression on monocytes through the p38 mitogen-activated protein kinase pathway. However, the cell surface interaction between prothrom...
Article
Background Valosin containing protein (p97/VCP) is an ATPase implicated in the degradation of ubiquitin-labelled proteins through the proteasome. We recently described a resistance to apoptotic cell death induced by proteasome inhibition and a hypersensitivity to autophagy-associated cell death under conditions of severe endoplasmic reticulum (ER)...
Article
Background Damage to bones is accelerated massively during the first two years after developing rheumatoid arthritis (RA), thus the patients with poor response to csDMARDs need early intervention by biological agents (Bio). However, few markers have been established for the prediction of future use of Bio on the diagnosis as RA. Objectives To clari...
Article
Background Pulmonary arterial hypertension (PAH) is of great clinical significance in connective tissue diseases (CTD) because of its high mortality. In particular, prognosis of PAH associated with systemic sclerosis (PAH-SSc) is extremely poor compared with PAH associated with other CTD (PAH-non-SSc). The reason, however, remains to be elucidated....