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Article ; Online: The monocyte-to-osteoclast transition in rheumatoid arthritis: Recent findings.

Iwamoto, Naoki / Kawakami, Atsushi

2022 Volume 13, Page(s) 998554

Abstract: Rheumatoid arthritis (RA) is an autoimmune disease characterized by joint inflammation leading to joint destruction and deformity. The crucial role of osteoclasts in the bone erosion in RA has been demonstrated. Deregulated osteoclastogenesis which is ... ...

Abstract	Rheumatoid arthritis (RA) is an autoimmune disease characterized by joint inflammation leading to joint destruction and deformity. The crucial role of osteoclasts in the bone erosion in RA has been demonstrated. Deregulated osteoclastogenesis which is affected by environmental factors including the inflammatory state, as well as genetic and epigenetic factors, is one of hallmarks of RA pathogenesis. An enhanced-monocyte-to-osteoclast transition plays an important role in osteoclast upregulation in RA because under specific stimuli, circulating monocytes might migrate to a specific location in the bones and fuse with each other to become mature multinucleated osteoclasts. To understand the mechanism of bone damage in RA and to develop novel treatments targeting osteoclast upregulation, it is important to clarify our understanding of the monocyte-to-osteoclast transition in RA. Several potential targets which inhibit both inflammation and osteoclastogenesis, as well as regulators that affect the monocyte-to-osteoclast transition have been revealed by recent studies. Here, we review the factors affecting osteoclastogenesis in RA, summarize the anti-osteoclastogenic effects of current RA treatments, and identify promising therapeutic targets relating to both inflammation and osteoclastogenesis.
MeSH term(s)	Arthritis, Rheumatoid ; Humans ; Inflammation/pathology ; Monocytes/pathology ; Osteoclasts/pathology ; Osteogenesis
Language	English
Publishing date	2022-09-12
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2606827-8
ISSN	1664-3224 ; 1664-3224
ISSN (online)	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2022.998554
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Article ; Online: Editorial: The role of monocytes/macrophages in autoimmunity and autoinflammation.

Kawakami, Atsushi / Iwamoto, Naoki / Fujio, Keishi

Frontiers in immunology

2022 Volume 13, Page(s) 1093430

MeSH term(s)	Autoimmunity ; Leukocytes
Language	English
Publishing date	2022-11-22
Publishing country	Switzerland
Document type	Editorial
ZDB-ID	2606827-8
ISSN	1664-3224 ; 1664-3224
ISSN (online)	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2022.1093430
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Article ; Online: Recent findings regarding the effects of microRNAs on fibroblast-like synovial cells in rheumatoid arthritis.

Iwamoto, Naoki / Kawakami, Atsushi

Immunological medicine

2019 Volume 42, Issue 4, Page(s) 156–161

Abstract: Rheumatoid arthritis (RA) is a systemic autoimmune disease with severe joint inflammation and destruction characterized by marked hyperplasia of the lining layer of the synovium. Fibroblast-like synovial cells (FLS) is a key cellular component within the ...

Abstract	Rheumatoid arthritis (RA) is a systemic autoimmune disease with severe joint inflammation and destruction characterized by marked hyperplasia of the lining layer of the synovium. Fibroblast-like synovial cells (FLS) is a key cellular component within the synovia; it plays pivotal roles in RA pathogenesis by unfavorable behaviors such as producing inflammatory cytokines and chemokines, and hyperproliferation. MicroRNAs are evolutionarily conserved small non-coding RNAs (length is 18-25 nucleotides) that regulate gene expression at the post-transcriptional level. There is increasing interest in the involvement of microRNAs in autoimmune diseases including RA. Recent studies revealed the regulation of the function of FLS by microRNAs. Here, we review the known functional microRNAs in RA and summarize the potential uses of these small molecules in the treatment of RA.
MeSH term(s)	Arthritis, Rheumatoid/genetics ; Cytokines ; Eukaryotic Initiation Factors ; Fibroblasts ; Gene Expression Regulation ; Humans ; Hyperplasia ; Inflammation Mediators ; MicroRNAs ; Mitochondrial Proteins ; Saccharomyces cerevisiae Proteins ; Synovial Membrane/cytology ; Synovial Membrane/pathology ; Synovial Membrane/physiology
Chemical Substances	Cytokines ; Eukaryotic Initiation Factors ; IFM1 protein, S cerevisiae ; Inflammation Mediators ; MicroRNAs ; Mitochondrial Proteins ; Saccharomyces cerevisiae Proteins
Language	English
Publishing date	2019-11-26
Publishing country	England
Document type	Journal Article ; Review
ISSN	2578-5826
ISSN (online)	2578-5826
DOI	10.1080/25785826.2019.1695490
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Article ; Online: Anti-melanoma Differentiation-associated Gene 5 Antibody-positive Dermatomyositis Presenting as Refractory Gingivitis at the First Clinical Manifestation.

Kawakami, Eiko / Uchida, Tomohisa / Iwamoto, Naoki / Hara, Kazusato / Egashira, Kazuhiro / Kawakami, Atsushi

Internal medicine (Tokyo, Japan)

2023 Volume 63, Issue 1, Page(s) 131–134

Abstract: We herein report a case of melanoma differentiation-associated gene 5 (MDA5) antibody-positive dermatomyositis that developed in a patient with refractory gingivitis. The diagnosis of anti-MDA5 antibody-positive dermatomyositis was made based on a ... ...

Abstract	We herein report a case of melanoma differentiation-associated gene 5 (MDA5) antibody-positive dermatomyositis that developed in a patient with refractory gingivitis. The diagnosis of anti-MDA5 antibody-positive dermatomyositis was made based on a characteristic skin rash, weakness of proximal muscles, interstitial pneumonia, and positivity for anti-MDA5 antibody. The patient was started on triple therapy with high-dose prednisolone, tacrolimus, and intravenous cyclophosphamide. After treatment, the refractory gingivitis disappeared, and the other skin rash and interstitial lung disease also improved. In the diagnosis and treatment of anti-MDA5 antibody-positive dermatomyositis, it is necessary to pay attention to the intraoral findings, including the gingiva.
MeSH term(s)	Humans ; Dermatomyositis/complications ; Dermatomyositis/diagnosis ; Dermatomyositis/drug therapy ; Interferon-Induced Helicase, IFIH1 ; Autoantibodies ; Lung Diseases, Interstitial/diagnosis ; Lung Diseases, Interstitial/drug therapy ; Lung Diseases, Interstitial/etiology ; Gingivitis/diagnosis ; Gingivitis/etiology ; Exanthema
Chemical Substances	Interferon-Induced Helicase, IFIH1 (EC 3.6.4.13) ; Autoantibodies
Language	English
Publishing date	2023-05-17
Publishing country	Japan
Document type	Case Reports ; Journal Article
ZDB-ID	32371-8
ISSN	1349-7235 ; 0021-5120 ; 0918-2918
ISSN (online)	1349-7235
ISSN	0021-5120 ; 0918-2918
DOI	10.2169/internalmedicine.1621-23
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Article ; Online: Association of denosumab with serum cytokines, chemokines, and bone-related factors in patients with rheumatoid arthritis: A post hoc analysis of a multicentre, open-label, randomised, parallel-group study.

Iwamoto, Naoki / Sato, Shuntaro / Furukawa, Kaori / Michitsuji, Toru / Shiraishi, Kazuteru / Watanabe, Kounosuke / Chiba, Ko / Osaki, Makoto / Kawakami, Atsushi

Modern rheumatology

2024

Abstract: Objectives: To clarify changes in serum cytokines, chemokines, and bone-related factors during denosumab treatment in rheumatoid arthritis (RA) patients.: Methods: This was a post hoc analysis of a multicentre, open-label, randomised, parallel-group ... ...

Abstract	Objectives: To clarify changes in serum cytokines, chemokines, and bone-related factors during denosumab treatment in rheumatoid arthritis (RA) patients. Methods: This was a post hoc analysis of a multicentre, open-label, randomised, parallel-group study. Patients were randomly assigned to continue treatment with conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs) plus receive treatment with denosumab (csDMARDs plus denosumab group) or to continue treatment with csDMARD therapy alone for 12 months. Serum biomarker levels were measured at baseline and 6 and 12 months. Results: Baseline and 6-month data from the csDMARDs plus denosumab (n = 22) and csDMARD therapy alone (n = 22) groups were analysed. Statistically significant changes from baseline were seen: dickkopf-related protein 1 decreased at 6 and 12 months (both groups); osteopontin decreased at 6 months in the csDMARDs plus denosumab group; osteopontin and soluble CD40 ligand increased at 6 and 12 months in the csDMARD therapy alone group; osteocalcin decreased at 6 and 12 months, epidermal growth factor decreased at 12 months, and macrophage-derived chemokine decreased at 6 months in the csDMARDs plus denosumab group; and interferon gamma-induced protein-10 increased at 12 months in the csDMARD therapy alone group. Conclusions: Denosumab may inhibit bone destruction by suppressing bone-related factors/chemokines.
Language	English
Publishing date	2024-01-13
Publishing country	England
Document type	Journal Article
ZDB-ID	2078157-X
ISSN	1439-7609 ; 1439-7595
ISSN (online)	1439-7609
ISSN	1439-7595
DOI	10.1093/mr/roae002
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Article ; Online: Denosumab improves bone mineral density and microarchitecture in rheumatoid arthritis: randomized controlled trial by HR-pQCT.

Chiba, Ko / Iwamoto, Naoki / Watanabe, Kounosuke / Shiraishi, Kazuteru / Saito, Kengo / Okubo, Naoki / Kawakami, Atsushi / Osaki, Makoto

Journal of bone and mineral metabolism

2023 Volume 41, Issue 6, Page(s) 797–806

Abstract: Introduction: This pre-specified exploratory analysis investigated the effect of denosumab on bone mineral density (BMD) and bone microarchitecture in patients with rheumatoid arthritis (RA) treated with conventional synthetic disease-modifying anti- ... ...

Abstract	Introduction: This pre-specified exploratory analysis investigated the effect of denosumab on bone mineral density (BMD) and bone microarchitecture in patients with rheumatoid arthritis (RA) treated with conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs). Materials and methods: In this open-label, parallel-group study, patients were randomly assigned (1:1) to continuous treatment with csDMARDs plus denosumab or continuous treatment with csDMARD therapy alone for 12 months. BMD and bone microarchitecture were measured by dual-energy X-ray absorptiometry (DXA) and high-resolution peripheral quantitative computed tomography (HR-pQCT). Results: Of 46 patients enrolled in the primary study, 43 were included in the full analysis set. The mean age was 65.3 years, 88.4% were female, and 60.5% had osteoporosis. Areal BMD of the lumbar spine increased from baseline to 6 and 12 months in both groups, but the increase was higher in the csDMARDs plus denosumab group. Areal BMD of the total hip and femoral neck increased from baseline to 6 and 12 months only in the csDMARDs plus denosumab group. Cortical volumetric BMD and cortical thickness of the distal tibia increased in the csDMARDs plus denosumab group at 6 and 12 months but decreased in the csDMARD therapy alone group. Trabecular bone parameters of the distal tibia improved only in the csDMARDs plus denosumab group at 12 months. Conclusion: Denosumab may be recommended for patients with RA treated with csDMARDs to increase BMD and improve bone microarchitecture.
MeSH term(s)	Humans ; Female ; Aged ; Male ; Bone Density ; Denosumab/therapeutic use ; Absorptiometry, Photon ; Arthritis, Rheumatoid/diagnostic imaging ; Arthritis, Rheumatoid/drug therapy ; Osteoporosis
Chemical Substances	Denosumab (4EQZ6YO2HI)
Language	English
Publishing date	2023-07-22
Publishing country	Japan
Document type	Randomized Controlled Trial ; Journal Article
ZDB-ID	1295123-7
ISSN	1435-5604 ; 0914-8779
ISSN (online)	1435-5604
ISSN	0914-8779
DOI	10.1007/s00774-023-01452-9
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Zs.A 4894: Show issues

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Article ; Online: Impact of SARS-CoV-2 mRNA vaccine on arthritis condition in rheumatoid arthritis.

Takatani, Ayuko / Iwamoto, Naoki / Koto, Serina / Aramaki, Toshiyuki / Terada, Kaoru / Ueki, Yukitaka / Kawakami, Atsushi / Eguchi, Katsumi

Frontiers in immunology

2023 Volume 14, Page(s) 1256655

Abstract: Background: The SARS-CoV-2 mRNA vaccine has been reported to cause various adverse reactions, including the development or exacerbation of autoimmune diseases, but the adverse reactions and the effects of the vaccines on disease activity in patients ... ...

Abstract	Background: The SARS-CoV-2 mRNA vaccine has been reported to cause various adverse reactions, including the development or exacerbation of autoimmune diseases, but the adverse reactions and the effects of the vaccines on disease activity in patients with rheumatoid arthritis (RA) remain unknown. We therefore investigated the arthritis condition in RA patients after SARS-CoV-2 vaccination. Methods: RA patients who visited our hospital from January to April 2022 completed a questionnaire regarding adverse reactions to the SARS-CoV-2 vaccine. We compared the frequency and duration of post-vaccination arthralgia between RA patients and health care workers in our hospital. For the RA patients who reported post-vaccination arthralgia, we collected medical records for the 6 months after vaccination. Results: Of the 1198 vaccinated RA patients, 256 (21.4%) had systemic inflammatory symptoms, 18 (1.5%) had allergies including urticaria and asthma, and 37 (3.1%) had arthralgia. A few patients had extra-articular manifestations such as acute exacerbation of interstitial lung disease. Compared with health care workers, RA patients more frequently developed arthralgia, and the arthralgia was longer lasting than that in controls: only 9 (0.8%) of the 1117 health care workers reported arthralgia, and all cases resolved within 3 days. Data from 31 of the 37 RA patients with post-vaccination arthralgia were further analyzed; in these patients, disease activity was highest after 2 months, and 10 patients required additional DMARDs within 6 months. The proportion of concomitant use of PSL at vaccination was higher in these patients. No patients on biological DMARDs or targeted synthetic DMARDs prior to vaccination needed additional DMARDs or a change of regimen. Conclusion: RA patients had more frequent and longer-lasting arthralgia after vaccination than healthy subjects, and one-third of patients with post-vaccination arthralgia required additional DMARDs. Although the SARS-CoV-2 mRNA vaccine was administered safely in most RA patients, in some patients RA symptoms may worsen after vaccination.
MeSH term(s)	Humans ; COVID-19 Vaccines/adverse effects ; SARS-CoV-2 ; COVID-19/prevention & control ; Arthritis, Rheumatoid/drug therapy ; Antirheumatic Agents/adverse effects ; Arthralgia/etiology ; Urticaria ; mRNA Vaccines
Chemical Substances	COVID-19 Vaccines ; Antirheumatic Agents ; mRNA Vaccines
Language	English
Publishing date	2023-08-25
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2606827-8
ISSN	1664-3224 ; 1664-3224
ISSN (online)	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2023.1256655
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Article ; Online: Evaluation of a renal risk score for Japanese patients with ANCA-associated glomerulonephritis in a multi-center cohort study.

Uchida, Tomohisa / Ichinose, Kunihiro / Yamashita, Ayuko / Muta, Kumiko / Kitamura, Mineaki / Sato, Shuntaro / Iwamoto, Naoki / Nishino, Tomoya / Kawakami, Atsushi

Frontiers in immunology

2023 Volume 14, Page(s) 1141407

Abstract: Background: In patients with anti-neutrophil cytoplasmic antibody (ANCA)-associated glomerulonephritis, prediction of renal survival should guide the choice of therapy, but a prediction of the histological classification has inconsistencies.: ... ...

Abstract	Background: In patients with anti-neutrophil cytoplasmic antibody (ANCA)-associated glomerulonephritis, prediction of renal survival should guide the choice of therapy, but a prediction of the histological classification has inconsistencies. Objectives: To evaluate the usefulness of renal risk score (RRS) for Japanese patients with ANCA-associated glomerulonephritis (AAGN) and compare the prediction for end-stage renal disease (ESRD) between RRS and the histological classification. Methods: We retrospectively analyzed 96 patients with AAGN who underwent a renal biopsy. Renal survival was categorized by RRS, and the histological classification was assessed separately. We compared the predictive values for RRS and the histological classification. Results: The median observational period was 37.5 (interquartile range [IQR] 21.5-77.0) months. The median RRS point at the time of renal biopsy was 2 (IQR 0-7.8), and the patients were categorized into low- (n = 29), medium- (n = 43), and high-risk groups (n = 24) using RRS. As expected, the renal prognosis was the worst in the "high-risk" group and the best in the "low-risk" group. In the histological classification, the survival deteriorated progressively from "focal" (best) to "mixed," "crescentic," and "sclerotic" (worst) classes, different from the order in the original proposal for this system. Multivariable Cox regression analysis revealed that RRS was independently associated with ESRD. The difference in prediction for renal survival between RRS and the histological classification was not significant using area under receiver-operating-characteristic curves. Conclusion: We evaluated the usefulness of RRS in Japanese patients with AAGN and found it a stable predictor of renal survival in such patients.
MeSH term(s)	Humans ; Antibodies, Antineutrophil Cytoplasmic ; Retrospective Studies ; East Asian People ; Follow-Up Studies ; Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis ; Glomerulonephritis ; Kidney Failure, Chronic/etiology ; Kidney Failure, Chronic/complications ; Risk Factors
Chemical Substances	Antibodies, Antineutrophil Cytoplasmic
Language	English
Publishing date	2023-02-28
Publishing country	Switzerland
Document type	Multicenter Study ; Journal Article
ZDB-ID	2606827-8
ISSN	1664-3224 ; 1664-3224
ISSN (online)	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2023.1141407
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Article ; Online: The double shared epitope: Its impact on clinical features and ultrasound findings in rheumatoid arthritis.

Michitsuji, Tohru / Fukui, Shoichi / Nishino, Ayako / Endo, Yushiro / Furukawa, Kaori / Shimizu, Toshimasa / Umeda, Masataka / Sumiyoshi, Remi / Koga, Tomohiro / Iwamoto, Naoki / Origuchi, Tomoki / Kawakami, Atsushi / Kawashiri, Shin-Ya

International journal of rheumatic diseases

2024 Volume 27, Issue 1, Page(s) e15030

Abstract: Objectives: The link between the HLA-DRB1 locus and the risk of rheumatoid arthritis (RA) shown in genome-wide association studies strengthens the shared epitope (SE) hypothesis. We aimed to assess the impact of the double dose of the SE (double SE) on ... ...

Abstract	Objectives: The link between the HLA-DRB1 locus and the risk of rheumatoid arthritis (RA) shown in genome-wide association studies strengthens the shared epitope (SE) hypothesis. We aimed to assess the impact of the double dose of the SE (double SE) on RA and explore its clinical associations, including the response to abatacept. Methods: We evaluated RA patients treated with csDMARDs or abatacept for HLA-DRB1 typing, clinical characteristics at baseline, and disease activity and ultrasound findings over 12 months. Results: Patients with the double SE (n = 12) had significantly higher anti-citrullinated protein antibody (ACPA) titers, higher total grayscale (GS) score, and power Doppler (PD) score at baseline than patients without the double SE. Patients with the double SE exhibited reduced rates of SDAI remission and pronounced improvements in multiple disease activity between baseline and 12 months, including SDAI, CDAI, total GS score, and total PD score. When focusing on abatacept-treated patients, the decreases in SDAI, CDAI, and total PD score between baseline and 12 months were significantly larger in patients with the double SE. Conclusions: Patients with the double SE exhibited distinct characteristics, increased disease activity, and improved response to abatacept treatment.
MeSH term(s)	Humans ; HLA-DRB1 Chains/genetics ; Abatacept/therapeutic use ; Epitopes ; Genome-Wide Association Study ; Arthritis, Rheumatoid/diagnostic imaging ; Arthritis, Rheumatoid/drug therapy ; Alleles
Chemical Substances	HLA-DRB1 Chains ; Abatacept (7D0YB67S97) ; Epitopes
Language	English
Publishing date	2024-01-30
Publishing country	England
Document type	Journal Article
ZDB-ID	2426924-4
ISSN	1756-185X ; 1756-1841
ISSN (online)	1756-185X
ISSN	1756-1841
DOI	10.1111/1756-185X.15030
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Article: [Abatacept].

Iwamoto, Naoki / Kawakami, Atsushi

Nihon rinsho. Japanese journal of clinical medicine

2016 Volume 74, Issue 6, Page(s) 968–973

Abstract: Abatacept (ABT) is a recombinant fusion protein comprising the extracellular domain of human CTLA4, which inhibits the activation of T cells. Several clinical trials have provided evidence of efficacy and safety of ABT in the patients with rheumatoid ... ...

Abstract	Abatacept (ABT) is a recombinant fusion protein comprising the extracellular domain of human CTLA4, which inhibits the activation of T cells. Several clinical trials have provided evidence of efficacy and safety of ABT in the patients with rheumatoid athritis (RA) with various clinical characteristics such as MTX inadequate responders (IR), TNF inhibitor-IR. Moreover, indirect comparison of ABT to other biologics reported in Cochrane review revealed that ABT has better safety profile in serious adverse events and serious infection Thus the features of ABT in the treatment of RA have gradually become apparent and knowledge of these features is helpful for better use of biologics. In this review we will discuss the efficacy and safety of ABT in the management of RA.
MeSH term(s)	Abatacept/administration & dosage ; Abatacept/adverse effects ; Abatacept/pharmacology ; Antirheumatic Agents/administration & dosage ; Antirheumatic Agents/adverse effects ; Antirheumatic Agents/pharmacology ; Arthritis, Rheumatoid/drug therapy ; Arthritis, Rheumatoid/immunology ; Biological Products/administration & dosage ; Biological Products/adverse effects ; Biological Products/pharmacology ; CTLA-4 Antigen ; Clinical Trials as Topic ; Disease Progression ; Drug Therapy, Combination ; Humans ; Lymphocyte Activation/drug effects ; Methotrexate/administration & dosage ; Molecular Targeted Therapy ; Product Surveillance, Postmarketing ; T-Lymphocytes/immunology
Chemical Substances	Antirheumatic Agents ; Biological Products ; CTLA-4 Antigen ; CTLA4 protein, human ; Abatacept (7D0YB67S97) ; Methotrexate (YL5FZ2Y5U1)
Language	Japanese
Publishing date	2016-06
Publishing country	Japan
Document type	English Abstract ; Journal Article ; Review
ZDB-ID	390903-7
ISSN	0047-1852
ISSN	0047-1852
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