99 results on '"Asashima H"'
Search Results
2. Neutrophils regulate ITPR2 levels in epithelia by direct injection of elastase
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Ogino, N, primary, Leite, M Fatima, additional, Kruglov, E, additional, Asashima, H, additional, Hafler, DA, additional, Ehrlich, BE, additional, and Nathanson, MH, additional
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- 2022
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3. cDNA microarray analysis identifies NR4A2 as a novel molecule involved in the pathogenesis of Sjögrenʼs syndrome
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Takahashi, H., Tsuboi, H., Asashima, H., Hirota, T., Kondo, Y., Moriyama, M., Matsumoto, I., Nakamura, S., and Sumida, T.
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- 2017
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4. RORγt antagonist suppresses M3 muscarinic acetylcholine receptor‐induced Sjögrenʼs syndrome‐like sialadenitis
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Tahara, M., Tsuboi, H., Segawa, S., Asashima, H., Iizuka‐Koga, M., Hirota, T., Takahashi, H., Kondo, Y., Matsui, M., Matsumoto, I., and Sumida, T.
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- 2017
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5. Pansclerotic morphea associated with hypohidrosis and anti-M3 muscarinic acetylcholine receptor antibodies
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Fujita-Tanaka, H., primary, Ogawa, Y., additional, Muro, Y., additional, Ogawa-Momohara, M., additional, Asashima, H., additional, Tsuboi, H., additional, Sumida, T., additional, and Akiyama, M., additional
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- 2018
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6. T FOLLICULAR HELPER CELLS IN BLOOD MIRROR SALIVARY GLAND-INFILTRATING T CELLS IN PRIMARY SJÖGREN'S SYNDROME.
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Abe, S., Tsuboi, H., Toko, H., Honda, F., Koido, A., Miki, H., Asashima, H., Kondo, Y., and Matsumoto, I.
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- 2023
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7. RORγt antagonist suppresses M3 muscarinic acetylcholine receptor-induced Sjögren's syndrome-like sialadenitis
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Tahara, M, primary, Tsuboi, H, additional, Segawa, S, additional, Asashima, H, additional, Iizuka-Koga, M, additional, Hirota, T, additional, Takahashi, H, additional, Kondo, Y, additional, Matsui, M, additional, Matsumoto, I, additional, and Sumida, T, additional
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- 2016
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8. Thermal changes of fingers after cold exposure
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Inokuma, S., Onishi, K., Kijima, Y., Natada, R., Matsubara, E., Asashima, H., Nakachi, S., Wakabayashi, N., Hagiwara, K., and Kobayashi, S.
- Published
- 2012
9. Magnetic resonance imaging can reveal fascial vasculitis in a patient with microscopic polyangiitis
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Takahashi, H, primary, Tsuboi, H, additional, Abe, S, additional, Yokosawa, M, additional, Hagiwara, S, additional, Asashima, H, additional, Hirota, T, additional, Umeda, N, additional, Kondo, Y, additional, Matsumoto, I, additional, and Sumida, T, additional
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- 2015
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10. [18F]fluorodeoxyglucose positron emission tomography/computed tomography can reveal subclinical prostatitis in a patient with IgG4-related disease
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Takahashi, H., primary, Tsuboi, H., additional, Ogishima, H., additional, Yokosawa, M., additional, Takahashi, H., additional, Yagishita, M., additional, Abe, S., additional, Hagiwara, S., additional, Asashima, H., additional, Hirota, T., additional, Umeda, N., additional, Kondo, Y., additional, Suzuki, T., additional, Matsumoto, I., additional, and Sumida, T., additional
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- 2015
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11. Predictors of the response to treatment in acute lupus hemophagocytic syndrome
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Takahashi, H, primary, Tsuboi, H, additional, Kurata, I, additional, Takahashi, H, additional, Inoue, S, additional, Ebe, H, additional, Yokosawa, M, additional, Hagiwara, S, additional, Hirota, T, additional, Asashima, H, additional, Kaneko, S, additional, Kawaguchi, H, additional, Kurashima, Y, additional, Miki, H, additional, Umeda, N, additional, Kondo, Y, additional, Ogishima, H, additional, Suzuki, T, additional, Matsumoto, I, additional, and Sumida, T, additional
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- 2014
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12. THU0044 The Suppressive Ability of Altered Peptide Ligands to M3R Induced Autoimmune Sialoadenitis in Vivo
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Asashima, H., primary, Tsuboi, H., additional, Iizuka, M., additional, Hagiya, C., additional, Hirota, T., additional, Kondo, Y., additional, Matsumoto, I., additional, and Sumida, T., additional
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- 2014
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13. THU0055 Interstitial pneumonitis associated with rheumatoid arthritis is more prevalent in aged male with a higher RF level, and frequently combined with emphysema
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Matsubara, E., primary, Okiyama, S., additional, Inokuma, S., additional, Onishi, K., additional, Nakachi, S., additional, Asashima, H., additional, Wakabayashi, K., additional, Hagiwara, K., additional, and Kobayashi, S., additional
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- 2013
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14. FRI0272 Analysis of molecular mechanism in igg4-related disease: comparison with sjögren’s syndrome
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Tsuboi, H., primary, Nakai, Y., additional, Iizuka, M., additional, Asashima, H., additional, Kondo, Y., additional, Tanaka, A., additional, Moriyama, M., additional, Matsumoto, I., additional, Yoshihara, T., additional, Nakamura, S., additional, Abe, K., additional, and Sumida, T., additional
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- 2013
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15. Predictors of the response to treatment in acute lupus hemophagocytic syndrome.
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Takahashi, H, Tsuboi, H, Kurata, I, Inoue, S, Ebe, H, Yokosawa, M, Hagiwara, S, Hirota, T, Asashima, H, Kaneko, S, Kawaguchi, H, Kurashima, Y, Miki, H, Umeda, N, Kondo, Y, Ogishima, H, Suzuki, T, Matsumoto, I, and Sumida, T
- Subjects
LUPUS erythematosus ,C-reactive protein ,HEMOGLOBINS ,ADRENOCORTICAL hormones ,FERRITIN ,PATIENTS ,THERAPEUTICS - Abstract
The article focuses on a study which aims to identify predictors for the response to the treatment of acute lupus hemophagocytic syndrome (ALHS). It states that patients treated with cyclosporine A (CsA), serum ferritn was higher in CsA responders. It mentions that low C-reactive protein (CRP) and high hemoglobin can predict positive response to corticosteroid monotherapy while high serum ferritin and low leukocyute count can predict response to CsA in patients with ALHS.
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- 2015
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16. Postpartum onset anti-MDA5 antibody-positive clinically amyopathic dermatomyositis; case-based review of perinatal onset anti-MDA5 antibody-positive dermatomyositis.
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Abe S, Tsuboi H, Toko H, Yagishita M, Ohyama A, Kitada A, Miki H, Asashima H, Kondo Y, and Matsumoto I
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- Female, Humans, Pregnancy, Postpartum Period, Autoantibodies blood, Dermatomyositis immunology, Dermatomyositis drug therapy, Dermatomyositis complications, Dermatomyositis diagnosis, Interferon-Induced Helicase, IFIH1 immunology
- Abstract
Anti-melanoma differentiation-associated protein 5 (MDA5) antibody positive clinically amyopathic dermatomyositis (CADM) is a subtype of inflammatory myopathy associated with a distinct clinical phenotype, characterized by rapidly progressing interstitial lung disease and limited muscle involvement. Although cases with onset of anti-MDA5 antibody positive CADM during pregnancy or the postpartum period are rare, they present unique challenges due to a potential pregnancy complications and the possible severity of the disease course. We present a case of anti-MDA5 antibody positive CADM that developed during the postpartum period following childbirth without any pregnancy complication. Additionally, we conducted a comprehensive review of case reports and series of similar cases to elucidate the clinical characteristics and outcomes. Our analysis revealed considerable variability in disease presentation, ranging from severe cases requiring multi-targeted therapy to well-controlled cases with less demanding treatments. The scarcity of evidence in this population underscores the importance of accumulating evidence from case series to inform treatment strategies. More precise prediction tools are needed to effectively manage this rare subset of patients., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)
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- 2024
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17. Mechanisms of age-related Treg dysfunction in an arthritic environment.
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Nishiyama T, Ohyama A, Miki H, Asashima H, Kondo Y, Tsuboi H, Ohno H, Shimano H, and Matsumoto I
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- Animals, Humans, Aged, Mice, Male, Middle Aged, Female, Signal Transduction, Adult, Arthritis, Experimental immunology, Interferon Type I immunology, Interferon Type I metabolism, Oxygen Consumption, Interferon-beta immunology, T-Lymphocytes, Regulatory immunology, Arthritis, Rheumatoid immunology, Aging immunology
- Abstract
Rheumatoid arthritis (RA) is an autoimmune disease characterized by a polyarticular synovitis. In recent years, elderly onset rheumatoid arthritis (EORA) has been increasing. Treg cells in RA have been reported to be dysfunctional, but the relationship between aging and their functional changes is unclear. Here, we found that Treg cells from EORA patients had increased percentages, but decreased activity compared to those from younger onset RA (YORA) patients. In experiments using arthritis model mice, decreased suppressive function and oxygen consumption rate (OCR) were observed in Treg cells only from old arthritic mice. Furthermore, type I interferon (IFN) signaling was upregulated in Treg cells from old GIA mice, and IFN-β decreased the suppressive function of Treg cells. Our findings demonstrate that increased type I IFN signaling in old Treg cells is induced only in the arthritic environment and relates to decreased suppressive function of Treg cells, gets involved in EORA., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2024 Elsevier Inc. All rights reserved.)
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- 2024
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18. Neutrophils insert elastase into hepatocytes to regulate calcium signaling in alcohol-associated hepatitis.
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Ogino N, Leite MF, Guerra MT, Kruglov E, Asashima H, Hafler DA, Ito T, Pereira JP, Peiffer BJ, Sun Z, Ehrlich BE, and Nathanson MH
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- Humans, Animals, Mice, Male, Cell Proliferation, Calcium Channels metabolism, Calcium Channels genetics, Female, Neutrophils metabolism, Neutrophils pathology, Hepatocytes metabolism, Hepatocytes pathology, Calcium Signaling, Hepatitis, Alcoholic metabolism, Hepatitis, Alcoholic pathology, Hepatitis, Alcoholic genetics, Pancreatic Elastase metabolism
- Abstract
Neutrophil infiltration occurs in a variety of liver diseases, but it is unclear how neutrophils and hepatocytes interact. Neutrophils generally use granule proteases to digest phagocytosed bacteria and foreign substances or neutralize them in neutrophil extracellular traps. In certain pathological states, granule proteases play a destructive role against the host as well. More recently, nondestructive actions of neutrophil granule proteins have been reported, such as modulation of tissue remodeling and metabolism. Here, we report a completely different mechanism by which neutrophils act nondestructively, by inserting granules directly into hepatocytes. Specifically, elastase-containing granules were transferred to hepatocytes where elastase selectively degraded intracellular calcium channels to reduce cell proliferation without cytotoxicity. In response, hepatocytes increased expression of Serpin E2 and A3, which inhibited elastase activity. Elastase insertion was seen in patient specimens of alcohol-associated hepatitis, and the relationship between elastase-mediated ITPR2 degradation and reduced cell proliferation was confirmed in mouse models. Moreover, neutrophils from patients with alcohol-associated hepatitis were more prone to degranulation and more potent in reducing calcium channel expression than neutrophils from healthy individuals. This nondestructive and reversible action on hepatocytes defines a previously unrecognized role for neutrophils in the transient regulation of epithelial calcium signaling mechanisms.
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- 2024
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19. Clinical importance of anti-Ro52 antibody for polymyositis and dermatomyositis.
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Sugita T, Tsuboi H, Sugita N, Akiyoshi R, Kuroda Y, Kawashima A, Kawashima F, Tabuchi D, Honda F, Ohyama A, Abe S, Kitada A, Asashima H, Miki H, Hagiwara S, Kondo Y, and Matsumoto I
- Abstract
Objectives: To clarify clinical features of anti-Ro52 antibody (Ab)-positive polymyositis (PM)/dermatomyositis (DM)., Patients and Methods: We retrospectively examined clinical features and status of anti-Ro52 Ab in patients with PM/DM admitted at the University of Tsukuba Hospital between January 2019 and February 2023. We compared anti-Ro52 Ab-positive and -negative groups., Results: A total of 40 patients were selected and analyzed. Median age at diagnosis was 61.5 (48.8-69.3) years and 34 cases were female. Twenty-three cases were PM and 17 cases were DM (including 6 clinically amyopathic dermatomyositis: CADM). Twenty-two cases were positive for anti-Ro52 Ab, 14 for anti-ARS Ab, and 6 for anti-MDA5 Ab. Interstitial lung disease (ILD) was detected in 29 cases, 9 of which were rapidly progressive. Glucocorticoid (GC)-resistant cardiomyopathy was detected in 6 cases, malignancy in 3 cases, and Sjögren's syndrome (SS) in 4 cases. Of the 22 anti-Ro52 Ab positive cases, only 3 were single-positive and the remaining 19 cases simultaneously had other autoantibodies. Comparing the anti-Ro52 Ab-positive and -negative groups, the frequencies of anti-ARS Ab positivity (63.6% vs. 0%), ILD (95.5% vs. 44.4%), GC-resistant cardiomyopathy (27.3% vs. 0%), concomitant use of immunosuppressants (95.5% vs. 55.6%), and levels of C-reactive protein (CRP) were significantly higher in the anti-Ro52 Ab-positive group (p<0.05). The frequencies of PM/DM, positivity of anti-MDA5 Ab, malignancies, and SS were comparable between groups., Conclusion: Anti-Ro52 Ab were frequently positive in PM/DM and anti-Ro52 Ab-positive patients showed significantly higher rates of anti-ARS Ab positivity and ILD, GC-resistant cardiomyopathy, concomitant use of immunosuppressants, and higher levels of CRP. Anti-Ro52 Ab may be useful as a severity marker in PM/DM., (© Japan College of Rheumatology 2024. Published by Oxford University Press. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site–for further information please contact journals.permissions@oup.com.)
- Published
- 2024
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20. An overlapping case of IgG4-related disease and systemic lupus erythematosus treated with belimumab: a case-based review.
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Iwamoto M, Asashima H, Sugita T, Kawashima F, Sugita N, Rai A, Kuroda Y, Kawashima A, Tabuchi D, Akao S, Sato R, Nishiyama T, Toko H, Honda F, Ohyama A, Kitada A, Abe S, Miki H, Hagiwara S, Kondo Y, Tsuboi H, and Matsumoto I
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- Male, Humans, Aged, Antibodies, Monoclonal, Humanized therapeutic use, Antibodies, Monoclonal therapeutic use, Glucocorticoids therapeutic use, Immunoglobulin G, Immunosuppressive Agents therapeutic use, Treatment Outcome, Immunoglobulin G4-Related Disease complications, Immunoglobulin G4-Related Disease diagnosis, Immunoglobulin G4-Related Disease drug therapy, Lupus Erythematosus, Systemic complications, Lupus Erythematosus, Systemic diagnosis, Lupus Erythematosus, Systemic drug therapy
- Abstract
IgG4-related disease (IgG4-RD) is a systemic condition in which IgG4
+ plasma cell infiltration and fibrosis cause organ swelling and lead to diverse clinical manifestations. Although IgG4-RD typically responds to glucocorticoids (GCs), relapse during tapering occurs and an early GC-sparing approach might therefore be beneficial. Systemic lupus erythematosus (SLE) is a chronic inflammatory disease with multiple symptoms that is also treated with GCs as a first-line therapy. Recently, belimumab, a recombinant human IgG-1λ monoclonal antibody that inhibits B-cell activating factor, was approved, but reports of use for IgG4-RD are scarce. Here, we present a rare case of IgG4-RD complicated with SLE which was successfully treated with belimumab. A 67-year-old man was diagnosed with IgG4-RD based on a high serum IgG4 level and histopathological findings. Furthermore, he had pericardial effusion on echocardiography, and laboratory tests revealed thrombocytopenia, autoimmune hemolysis, positive anti-nuclear antibodies, positive anti-DNA antibodies, and hypocomplementemia. These data led to an SLE diagnosis. Treatment was started with prednisolone at 40 mg/day, plus hydroxychloroquine, which initially improved both the SLE and IgG4-RD symptoms. During the GC tapering, belimumab was added and clinical symptoms resolved completely. Our case and the literature review summarize reported rare overlapping cases of IgG4-RD and SLE and suggest that belimumab is a promising candidate for the treatment of IgG4-RD., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)- Published
- 2024
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21. Multidrug-resistant IgA Vasculitis with Gastrointestinal Symptoms Successfully Treated with Intravenous Cyclophosphamide and Maintained with Mycophenolate Mofetil.
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Miki H, Tsuboi H, Kawashima F, Sugita T, Nishiyama T, Kuroda Y, Sawabe T, Uematsu N, Terasaki M, Kitada A, Honda F, Ohyama A, Yagishita M, Asashima H, Hagiwara S, Kondo Y, and Matsumoto I
- Subjects
- Female, Humans, Adolescent, Mycophenolic Acid therapeutic use, Immunosuppressive Agents therapeutic use, Cyclophosphamide therapeutic use, Azathioprine, Remission Induction, IgA Vasculitis, Lupus Nephritis
- Abstract
We present the case of a 17-year-old woman with IgA vasculitis (IgAV) who presented with relapsing gastrointestinal (GI) symptoms that were refractory to glucocorticoid and combination therapy with cyclosporine A, azathioprine or mycophenolate mofetil (MMF). The patient responded well to remission induction with intravenous cyclophosphamide (IVCY) and was successfully maintained with MMF. Remission induction with IVCY followed by maintenance therapy with MMF was effective in a patient with multidrug-resistant IgAV with GI lesions.
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- 2024
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22. Role of inter-alpha-trypsin inhibitor heavy chain 4 and its citrullinated form in experimental arthritis murine models.
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Iwai T, Ohyama A, Osada A, Nishiyama T, Shimizu M, Miki H, Asashima H, Kondo Y, Tsuboi H, Mizuno S, Takahashi S, Ishigami A, and Matsumoto I
- Subjects
- Animals, Humans, Mice, Disease Models, Animal, Mice, Inbred C57BL, Proteins, Alpha-Globulins, Arthritis, Experimental, Arthritis, Rheumatoid
- Abstract
Inter-α-trypsin inhibitor heavy chain 4 (ITIH4) is a major protein in serum and reported to be upregulated at the onset of rheumatoid arthritis (RA). Its citrullinated form, cit-ITIH4, is specifically found in the serum and synovial fluid of patients with RA. However, the detailed function of ITIH4 in arthritis remains unknown. The aim of this study was to clarify the role of ITIH4 and cit-ITIH4 using experimental arthritis models. ITIH4 and cit-ITIH4 expression was examined in steady-state mice and two different arthritis models, and their pathological effects were examined in Itih4-deficient mice. In naïve C57BL/6 (WT) mice, ITIH4 was expressed as mRNA in the liver and the lung and was expressed as protein in serum and hepatocytes. In K/BxN serum transferred arthritis (K/BxN-STA) and collagen-induced arthritis (CIA), ITIH4 and cit-ITIH4 in sera were increased before the onset of arthritis, and cit-ITIH4 was further increased at the peak of arthritis. In Itih4-deficient mice, citrullinated proteins in serum and joints, especially 120 kDa protein, were clearly diminished; however, there was no significant difference in arthritis severity between WT and itih-/- mice either in the K/BxN-STA or CIA model. CIA mice also exhibited pulmonary lesions and itih4-/- mice tended to show enhanced inflammatory cell aggregation compared to WT mice. Neutrophils in the lungs of itih4-/- mice were significantly increased compared to WT mice. In summary, ITIH4 itself did not alter the severity of arthritis but may inhibit autoimmune inflammation via suppression of neutrophil recruitment., (© The Author(s) 2024. Published by Oxford University Press on behalf of the British Society for Immunology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)
- Published
- 2024
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23. Microfluidic Immuno-Serolomic Assay Reveals Systems Level Association with COVID-19 Pathology and Vaccine Protection.
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Kim D, Biancon G, Bai Z, VanOudenhove J, Liu Y, Kothari S, Gowda L, Kwan JM, Buitrago-Pocasangre NC, Lele N, Asashima H, Racke MK, Wilson JE, Givens TS, Tomayko MM, Schulz WL, Longbrake EE, Hafler DA, Halene S, and Fan R
- Subjects
- Humans, Microfluidics, Immunoglobulin G, COVID-19 prevention & control, Vaccines, Hematologic Neoplasms
- Abstract
How to develop highly informative serology assays to evaluate the quality of immune protection against coronavirus disease-19 (COVID-19) has been a global pursuit over the past years. Here, a microfluidic high-plex immuno-serolomic assay is developed to simultaneously measure50 plasma or serum samples for50 soluble markers including 35proteins, 11 anti-spike/receptor binding domian (RBD) IgG antibodies spanningmajor variants, and controls. This assay demonstrates the quintuplicate test in a single run with high throughput, low sample volume, high reproducibilityand accuracy. It is applied to the measurement of 1012 blood samples including in-depth analysis of sera from 127 patients and 21 healthy donors over multiple time points, either with acute COVID infection or vaccination. The protein analysis reveals distinct immune mediator modules that exhibit a reduced degree of diversity in protein-protein cooperation in patients with hematologic malignancies or receiving B cell depletion therapy. Serological analysis identifies that COVID-infected patients with hematologic malignancies display impaired anti-RBD antibody response despite high level of anti-spike IgG, which can be associated with limited clonotype diversity and functional deficiency in B cells. These findings underscore the importance to individualize immunization strategies for these high-risk patients and provide an informative tool to monitor their responses at the systems level., (© 2023 The Authors. Small Methods published by Wiley-VCH GmbH.)
- Published
- 2023
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24. High-plex protein and whole transcriptome co-mapping at cellular resolution with spatial CITE-seq.
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Liu Y, DiStasio M, Su G, Asashima H, Enninful A, Qin X, Deng Y, Nam J, Gao F, Bordignon P, Cassano M, Tomayko M, Xu M, Halene S, Craft JE, Hafler D, and Fan R
- Subjects
- Animals, Mice, Humans, Epitopes, RNA, Messenger, Gene Expression Profiling methods, Transcriptome genetics, Single-Cell Analysis
- Abstract
In this study, we extended co-indexing of transcriptomes and epitopes (CITE) to the spatial dimension and demonstrated high-plex protein and whole transcriptome co-mapping. We profiled 189 proteins and whole transcriptome in multiple mouse tissue types with spatial CITE sequencing and then further applied the method to measure 273 proteins and transcriptome in human tissues, revealing spatially distinct germinal center reactions in tonsil and early immune activation in skin at the Coronavirus Disease 2019 mRNA vaccine injection site., (© 2023. The Author(s).)
- Published
- 2023
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25. Prior cycles of anti-CD20 antibodies affect antibody responses after repeated SARS-CoV-2 mRNA vaccination.
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Asashima H, Kim D, Wang K, Lele N, Buitrago-Pocasangre NC, Lutz R, Cruz I, Raddassi K, Ruff WE, Racke MK, Wilson JE, Givens TS, Grifoni A, Weiskopf D, Sette A, Kleinstein SH, Montgomery RR, Shaw AC, Li F, Fan R, Hafler DA, Tomayko MM, and Longbrake EE
- Subjects
- Humans, Aged, SARS-CoV-2, BNT162 Vaccine, Vaccination, Antibodies, Monoclonal, Antilymphocyte Serum, RNA, Messenger, Antibody Formation, COVID-19 prevention & control
- Abstract
BACKGROUNDWhile B cell depletion is associated with attenuated antibody responses to SARS-CoV-2 mRNA vaccination, responses vary among individuals. Thus, elucidating the factors that affect immune responses after repeated vaccination is an important clinical need.METHODSWe evaluated the quality and magnitude of the T cell, B cell, antibody, and cytokine responses to a third dose of BNT162b2 or mRNA-1273 mRNA vaccine in patients with B cell depletion.RESULTSIn contrast with control individuals (n = 10), most patients on anti-CD20 therapy (n = 48) did not demonstrate an increase in spike-specific B cells or antibodies after a third dose of vaccine. A third vaccine elicited significantly increased frequencies of spike-specific non-naive T cells. A small subset of B cell-depleted individuals effectively produced spike-specific antibodies, and logistic regression models identified time since last anti-CD20 treatment and lower cumulative exposure to anti-CD20 mAbs as predictors of those having a serologic response. B cell-depleted patients who mounted an antibody response to 3 vaccine doses had persistent humoral immunity 6 months later.CONCLUSIONThese results demonstrate that serial vaccination strategies can be effective for a subset of B cell-depleted patients.FUNDINGThe NIH (R25 NS079193, P01 AI073748, U24 AI11867, R01 AI22220, UM 1HG009390, P01 AI039671, P50 CA121974, R01 CA227473, U01CA260507, 75N93019C00065, K24 AG042489), NIH HIPC Consortium (U19 AI089992), the National Multiple Sclerosis Society (CA 1061-A-18, RG-1802-30153), the Nancy Taylor Foundation for Chronic Diseases, Erase MS, and the Claude D. Pepper Older Americans Independence Center at Yale (P30 AG21342).
- Published
- 2023
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26. PD-1 high CXCR5 - CD4 + peripheral helper T cells promote CXCR3 + plasmablasts in human acute viral infection.
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Asashima H, Mohanty S, Comi M, Ruff WE, Hoehn KB, Wong P, Klein J, Lucas C, Cohen I, Coffey S, Lele N, Greta L, Raddassi K, Chaudhary O, Unterman A, Emu B, Kleinstein SH, Montgomery RR, Iwasaki A, Dela Cruz CS, Kaminski N, Shaw AC, Hafler DA, and Sumida TS
- Subjects
- Humans, CD4-Positive T-Lymphocytes, T-Lymphocytes, Helper-Inducer, Plasma Cells metabolism, Receptors, CXCR5, Receptors, CXCR3 metabolism, Programmed Cell Death 1 Receptor metabolism, COVID-19 metabolism
- Abstract
T cell-B cell interaction is the key immune response to protect the host from severe viral infection. However, how T cells support B cells to exert protective humoral immunity in humans is not well understood. Here, we use COVID-19 as a model of acute viral infections and analyze CD4
+ T cell subsets associated with plasmablast expansion and clinical outcome. Peripheral helper T cells (Tph cells; denoted as PD-1high CXCR5- CD4+ T cells) are significantly increased, as are plasmablasts. Tph cells exhibit "B cell help" signatures and induce plasmablast differentiation in vitro. Interestingly, expanded plasmablasts show increased CXCR3 expression, which is positively correlated with higher frequency of activated Tph cells and better clinical outcome. Mechanistically, Tph cells help B cell differentiation and produce more interferon γ (IFNγ), which induces CXCR3 expression on plasmablasts. These results elucidate a role for Tph cells in regulating protective B cell response during acute viral infection., Competing Interests: Declaration of interests D.A.H. has received research funding from Bristol-Myers Squibb, Novartis, Sanofi, and Genentech. He has been a consultant for Bayer Pharmaceuticals, Bristol Myers Squibb, Compass Therapeutics, EMD Serono, Genentech, Juno Therapeutics, Novartis Pharmaceuticals, Proclara Biosciences, Sage Therapeutics, and Sanofi Genzyme. Further information regarding funding is available at https://openpaymentsdata.cms.gov/physician/166753/general-payments. N.K. reports personal fees from Boehringer Ingelheim, Third Rock, Pliant, Samumed, NuMedii, Indalo, Theravance, LifeMax, Three Lake Partners, and RohBar in the last 36 months and Equity in Pliant. N.K. is also a recipient of a grant from Veracyte and non-financial support from Miragen. In addition, N.K. has patents on New Therapies in Pulmonary Fibrosis and ARDS (unlicensed) and Peripheral Blood Gene Expression as biomarkers in IPF (licensed to biotech), all outside the submitted work. S.H.K. receives consulting fees from Northrop Grumman. K.B.H. receives consulting fees from Prellis Biologics., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)- Published
- 2023
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27. Impaired TIGIT expression on B cells drives circulating follicular helper T cell expansion in multiple sclerosis.
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Asashima H, Axisa PP, Pham THG, Longbrake EE, Ruff WE, Lele N, Cohen I, Raddassi K, Sumida TS, and Hafler DA
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- CD40 Ligand, Cell Proliferation, Humans, Ligands, Receptors, Immunologic genetics, T Follicular Helper Cells, T-Lymphocytes, Helper-Inducer, Transcription Factors, B-Lymphocytes, Interleukin-17, Multiple Sclerosis genetics, Multiple Sclerosis pathology
- Abstract
B cell depletion in patients with relapsing-remitting multiple sclerosis (RRMS) markedly prevents new MRI-detected lesions and disease activity, suggesting the hypothesis that altered B cell function leads to the activation of T cells driving disease pathogenesis. Here, we performed comprehensive analyses of CD40 ligand- (CD40L-) and IL-21-stimulated memory B cells from patients with MS and healthy age-matched controls, modeling the help of follicular helper T cells (Tfh cells), and found a differential gene expression signature in multiple B cell pathways. Most striking was the impaired TIGIT expression on MS-derived B cells mediated by dysregulation of the transcription factor TCF4. Activated circulating Tfh cells (cTfh cells) expressed CD155, the ligand of TIGIT, and TIGIT on B cells revealed their capacity to suppress the proliferation of IL-17-producing cTfh cells via the TIGIT/CD155 axis. Finally, CCR6+ cTfh cells were significantly increased in patients with MS, and their frequency was inversely correlated with that of TIGIT+ B cells. Together, these data suggest that the dysregulation of negative feedback loops between TIGIT+ memory B cells and cTfh cells in MS drives the activated immune system in this disease.
- Published
- 2022
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28. Microfluidic immuno-serology assay revealed a limited diversity of protection against COVID-19 in patients with altered immunity.
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Kim D, Biancon G, Bai Z, VanOudenhove J, Liu Y, Kothari S, Gowda L, Kwan JM, Buitrago-Pocasangre NC, Lele N, Asashima H, Racke MK, Wilson JE, Givens TS, Tomayko MM, Schulz WL, Longbrake EE, Hafler DA, Halene S, and Fan R
- Abstract
The immune response to SARS-CoV-2 for patients with altered immunity such as hematologic malignancies and autoimmune disease may differ substantially from that in general population. These patients remain at high risk despite wide-spread adoption of vaccination. It is critical to examine the differences at the systems level between the general population and the patients with altered immunity in terms of immunologic and serological responses to COVID-19 infection and vaccination. Here, we developed a novel microfluidic chip for high-plex immuno-serological assay to simultaneously measure up to 50 plasma or serum samples for up to 50 soluble markers including 35 plasma proteins, 11 anti-spike/RBD IgG antibodies spanning all major variants, and controls. Our assay demonstrated the quintuplicate test in a single run with high throughput, low sample volume input, high reproducibility and high accuracy. It was applied to the measurement of 1,012 blood samples including in-depth analysis of sera from 127 patients and 21 healthy donors over multiple time points, either with acute COVID infection or vaccination. The protein association matrix analysis revealed distinct immune mediator protein modules that exhibited a reduced degree of diversity in protein-protein cooperation in patients with hematologic malignancies and patients with autoimmune disorders receiving B cell depletion therapy. Serological analysis identified that COVID infected patients with hematologic malignancies display impaired anti-RBD antibody response despite high level of anti-spike IgG, which could be associated with limited clonotype diversity and functional deficiency in B cells and was further confirmed by single-cell BCR and transcriptome sequencing. These findings underscore the importance to individualize immunization strategy for these high-risk patients and provide an informative tool to monitor their responses at the systems level.
- Published
- 2022
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29. Combining Cellular Immunology With RNAseq to Identify Novel Chlamydia T-Cell Subset Signatures.
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Johnson RM, Asashima H, Mohanty S, and Shaw AC
- Subjects
- Animals, B-Lymphocytes, CD4-Positive T-Lymphocytes, Chlamydia trachomatis, Genitalia pathology, Mice, Mice, Inbred C57BL, T-Lymphocyte Subsets, Chlamydia Infections microbiology
- Abstract
Chlamydia trachomatis serovars A-L cause important diseases of the eyes and reproductive tract by infecting epithelium lining those organs. A major hurdle for vaccine trials is finding a surrogate biomarker for protective immunity. Investigational data argues for T-cell biomarker(s) reflecting mucosal adaption, cytokine polarization, B-cell help, antibacterial effector mechanisms, or some combination thereof. A human investigation and 2 mouse studies link IL-13 to protection from infection/immunopathology. We performed RNAseq on T cells resident in spleens and genital tracts of naturally immune mice. CD4 signatures were consistent with helper function that differed by site including a genital tract-specific Fgl2 signal. The genital tract CD8 signature featured IL-10 and promotion of healing/scarring with a unique transcription of granzyme A. The RNAseq data was used to refine previously published CD4γ13 and CD8γ13 transcriptomes derived from protective T-cell clones, potentially identifying practicable T-cell subset signatures for assessing Chlamydia vaccine candidates., (© The Author(s) 2022. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)
- Published
- 2022
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30. Spatial-CITE-seq: spatially resolved high-plex protein and whole transcriptome co-mapping.
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Liu Y, DiStasio M, Su G, Asashima H, Enninful A, Qin X, Deng Y, Bordignon P, Cassano M, Tomayko M, Xu M, Halene S, Craft JE, Hafler D, and Fan R
- Abstract
We present spatial-CITE-seq for high-plex protein and whole transcriptome co-mapping, which was firstly demonstrated for profiling 198 proteins and transcriptome in multiple mouse tissue types. It was then applied to human tissues to measure 283 proteins and transcriptome that revealed spatially distinct germinal center reaction in tonsil and early immune activation in skin at the COVID-19 mRNA vaccine injection site. Spatial-CITE-seq may find a range of applications in biomedical research.
- Published
- 2022
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31. Single-cell multi-omics reveals dyssynchrony of the innate and adaptive immune system in progressive COVID-19.
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Unterman A, Sumida TS, Nouri N, Yan X, Zhao AY, Gasque V, Schupp JC, Asashima H, Liu Y, Cosme C Jr, Deng W, Chen M, Raredon MSB, Hoehn KB, Wang G, Wang Z, DeIuliis G, Ravindra NG, Li N, Castaldi C, Wong P, Fournier J, Bermejo S, Sharma L, Casanovas-Massana A, Vogels CBF, Wyllie AL, Grubaugh ND, Melillo A, Meng H, Stein Y, Minasyan M, Mohanty S, Ruff WE, Cohen I, Raddassi K, Niklason LE, Ko AI, Montgomery RR, Farhadian SF, Iwasaki A, Shaw AC, van Dijk D, Zhao H, Kleinstein SH, Hafler DA, Kaminski N, and Dela Cruz CS
- Subjects
- Adaptive Immunity drug effects, Adaptive Immunity genetics, Aged, Antibodies, Monoclonal, Humanized therapeutic use, CD4-Positive T-Lymphocytes drug effects, CD4-Positive T-Lymphocytes immunology, CD4-Positive T-Lymphocytes metabolism, CD8-Positive T-Lymphocytes drug effects, CD8-Positive T-Lymphocytes immunology, CD8-Positive T-Lymphocytes metabolism, COVID-19 genetics, Cells, Cultured, Female, Gene Expression Regulation drug effects, Gene Expression Regulation immunology, Humans, Immunity, Innate drug effects, Immunity, Innate genetics, Male, RNA-Seq methods, Receptors, Antigen, B-Cell genetics, Receptors, Antigen, B-Cell immunology, Receptors, Antigen, T-Cell genetics, Receptors, Antigen, T-Cell immunology, SARS-CoV-2 drug effects, SARS-CoV-2 physiology, COVID-19 Drug Treatment, Adaptive Immunity immunology, COVID-19 immunology, Gene Expression Profiling methods, Immunity, Innate immunology, SARS-CoV-2 immunology, Single-Cell Analysis methods
- Abstract
Dysregulated immune responses against the SARS-CoV-2 virus are instrumental in severe COVID-19. However, the immune signatures associated with immunopathology are poorly understood. Here we use multi-omics single-cell analysis to probe the dynamic immune responses in hospitalized patients with stable or progressive course of COVID-19, explore V(D)J repertoires, and assess the cellular effects of tocilizumab. Coordinated profiling of gene expression and cell lineage protein markers shows that S100A
hi /HLA-DRlo classical monocytes and activated LAG-3hi T cells are hallmarks of progressive disease and highlights the abnormal MHC-II/LAG-3 interaction on myeloid and T cells, respectively. We also find skewed T cell receptor repertories in expanded effector CD8+ clones, unmutated IGHG+ B cell clones, and mutated B cell clones with stable somatic hypermutation frequency over time. In conclusion, our in-depth immune profiling reveals dyssynchrony of the innate and adaptive immune interaction in progressive COVID-19., (© 2022. The Author(s).)- Published
- 2022
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32. T-bet represses collagen-induced arthritis by suppressing Th17 lineage commitment through inhibition of RORγt expression and function.
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Shimizu M, Kondo Y, Tanimura R, Furuyama K, Yokosawa M, Asashima H, Tsuboi H, Matsumoto I, and Sumida T
- Subjects
- Animals, Base Sequence, CD4-Positive T-Lymphocytes cytology, Cell Differentiation, Cell Lineage, Cell Separation, Coculture Techniques, Collagen chemistry, Dendritic Cells cytology, Flow Cytometry, Gene Expression Regulation, Immunoglobulin G chemistry, Interleukin-17 biosynthesis, Male, Mice, Mice, Inbred C57BL, Mice, Knockout, Rheumatology, Thymus Gland metabolism, Transcriptome, Arthritis, Experimental immunology, Nuclear Receptor Subfamily 1, Group F, Member 3 metabolism, Th17 Cells cytology
- Abstract
T-bet is a key transcription factor for the T helper 1 lineage and its expression level is negatively correlated to inflammation in patients with rheumatoid arthritis (RA). Our previous study using T-bet transgenic mice revealed over-expression of T-bet completely suppressed collagen-induced arthritis (CIA), a murine model of RA, indicating a potential suppressive role of T-bet in the pathogenesis of autoimmune arthritis. Here, we show T-bet-deficiency exacerbated CIA. T-bet in CD4 + T cells, but not in CD11c + dendritic cells, was critical for regulating the production of IL-17A, IL-17F, IL-22, and TNFα from CD4 + T cells. T-bet-deficient CD4 + T cells showed higher RORγt expression and increased IL-17A production in RORγt-positive cells after CII immunization. In addition, T-bet-deficient naïve CD4 + T cells showed accelerated Th17 differentiation in vitro. CIA induced in CD4-Cre T-bet
fl/fl (cKO) mice was more severe and T-bet-deficient CD4 + T cells in the arthritic joints of cKO mice showed higher RORγt expression and increased IL-17A production. Transcriptome analysis of T-bet-deficient CD4 + T cells revealed that expression levels of Th17-related genes were selectively increased. Our results indicate that T-bet in CD4 + T cells repressed RORγt expression and function resulting in suppression of arthritogenic Th17 cells and CIA., (© 2021. The Author(s).)- Published
- 2021
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33. Cutting Edge: Distinct B Cell Repertoires Characterize Patients with Mild and Severe COVID-19.
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Hoehn KB, Ramanathan P, Unterman A, Sumida TS, Asashima H, Hafler DA, Kaminski N, Dela Cruz CS, Sealfon SC, Bukreyev A, and Kleinstein SH
- Subjects
- Cohort Studies, Humans, SARS-CoV-2 immunology, B-Lymphocytes immunology, COVID-19 immunology
- Abstract
Protective immunity against COVID-19 likely depends on the production of SARS-CoV-2-specific plasma cells and memory B cells postinfection or postvaccination. Previous work has found that germinal center reactions are disrupted in severe COVID-19. This may adversely affect long-term immunity against reinfection. Consistent with an extrafollicular B cell response, patients with severe COVID-19 have elevated frequencies of clonally expanded, class-switched, unmutated plasmablasts. However, it is unclear whether B cell populations in individuals with mild COVID-19 are similarly skewed. In this study, we use single-cell RNA sequencing of B cells to show that in contrast to patients with severe COVID-19, subjects with mildly symptomatic COVID-19 have B cell repertoires enriched for clonally diverse, somatically hypermutated memory B cells ∼30 d after the onset of symptoms. This provides evidence that B cell responses are less disrupted in mild COVID-19 and result in the production of memory B cells., (Copyright © 2021 by The American Association of Immunologists, Inc.)
- Published
- 2021
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34. Immune dysregulation and autoreactivity correlate with disease severity in SARS-CoV-2-associated multisystem inflammatory syndrome in children.
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Ramaswamy A, Brodsky NN, Sumida TS, Comi M, Asashima H, Hoehn KB, Li N, Liu Y, Shah A, Ravindra NG, Bishai J, Khan A, Lau W, Sellers B, Bansal N, Guerrerio P, Unterman A, Habet V, Rice AJ, Catanzaro J, Chandnani H, Lopez M, Kaminski N, Dela Cruz CS, Tsang JS, Wang Z, Yan X, Kleinstein SH, van Dijk D, Pierce RW, Hafler DA, and Lucas CL
- Subjects
- Adolescent, Alarmins immunology, Autoantibodies immunology, CD8-Positive T-Lymphocytes immunology, Child, Child, Preschool, Cytotoxicity, Immunologic genetics, Endothelium immunology, Endothelium pathology, Humans, Killer Cells, Natural immunology, Myeloid Cells immunology, Plasma Cells immunology, Receptors, Antigen, T-Cell genetics, Receptors, Antigen, T-Cell immunology, Severity of Illness Index, COVID-19 immunology, COVID-19 pathology, SARS-CoV-2 immunology, Systemic Inflammatory Response Syndrome immunology, Systemic Inflammatory Response Syndrome pathology
- Abstract
Multisystem inflammatory syndrome in children (MIS-C) is a life-threatening post-infectious complication occurring unpredictably weeks after mild or asymptomatic SARS-CoV-2 infection. We profiled MIS-C, adult COVID-19, and healthy pediatric and adult individuals using single-cell RNA sequencing, flow cytometry, antigen receptor repertoire analysis, and unbiased serum proteomics, which collectively identified a signature in MIS-C patients that correlated with disease severity. Despite having no evidence of active infection, MIS-C patients had elevated S100A-family alarmins and decreased antigen presentation signatures, indicative of myeloid dysfunction. MIS-C patients showed elevated expression of cytotoxicity genes in NK and CD8
+ T cells and expansion of specific IgG-expressing plasmablasts. Clinically severe MIS-C patients displayed skewed memory T cell TCR repertoires and autoimmunity characterized by endothelium-reactive IgG. The alarmin, cytotoxicity, TCR repertoire, and plasmablast signatures we defined have potential for application in the clinic to better diagnose and potentially predict disease severity early in the course of MIS-C., Competing Interests: Declaration of interests D.A.H. has received research funding from Bristol-Myers Squibb, Novartis, Sanofi, and Genentech. He has been a consultant for Bayer Pharmaceuticals, Bristol Myers Squibb, Compass Therapeutics, EMD Serono, Genentech, Juno Therapeutics, Novartis Pharmaceuticals, Proclara Biosciences, Sage Therapeutics, and Sanofi Genzyme. Further information regarding funding is available on: https://openpaymentsdata.cms.gov/physician/166753/general-payments. N.K. reports personal fees from Boehringer Ingelheim, Third Rock, Pliant, Samumed, NuMedii, Indalo, Theravance, LifeMax, Three Lake Partners, RohBar in the last 36 months, and Equity in Pliant. N.K. is also a recipient of a grant from Veracyte and non-financial support from Miragen. All outside the submitted work; In addition, N.K. has patents on New Therapies in Pulmonary Fibrosis and ARDS (unlicensed) and Peripheral Blood Gene Expression as biomarkers in IPF (licensed to biotech). S.H.K. receives consulting fees from Northrop Grumman. K.B.H. receives consulting fees from Prellis Biologics. B.S. is a former SomaLogic, Inc. (Boulder, CO, USA) employee and a company shareholder. All other authors declared that they have no competing interests., (Copyright © 2021 Elsevier Inc. All rights reserved.)- Published
- 2021
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35. Post-infectious inflammatory disease in MIS-C features elevated cytotoxicity signatures and autoreactivity that correlates with severity.
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Ramaswamy A, Brodsky NN, Sumida TS, Comi M, Asashima H, Hoehn KB, Li N, Liu Y, Shah A, Ravindra NG, Bishai J, Khan A, Lau W, Sellers B, Bansal N, Guerrerio P, Unterman A, Habet V, Rice AJ, Catanzaro J, Chandnani H, Lopez M, Kaminski N, Dela Cruz CS, Tsang JS, Wang Z, Yan X, Kleinstein SH, van Dijk D, Pierce RW, Hafler DA, and Lucas CL
- Abstract
Multisystem inflammatory syndrome in children (MIS-C) is a life-threatening post-infectious complication occurring unpredictably weeks after mild or asymptomatic SARS-CoV2 infection in otherwise healthy children. Here, we define immune abnormalities in MIS-C compared to adult COVID-19 and pediatric/adult healthy controls using single-cell RNA sequencing, antigen receptor repertoire analysis, unbiased serum proteomics, and in vitro assays. Despite no evidence of active infection, we uncover elevated S100A-family alarmins in myeloid cells and marked enrichment of serum proteins that map to myeloid cells and pathways including cytokines, complement/coagulation, and fluid shear stress in MIS-C patients. Moreover, NK and CD8 T cell cytotoxicity genes are elevated, and plasmablasts harboring IgG1 and IgG3 are expanded. Consistently, we detect elevated binding of serum IgG from severe MIS-C patients to activated human cardiac microvascular endothelial cells in culture. Thus, we define immunopathology features of MIS-C with implications for predicting and managing this SARS-CoV2-induced critical illness in children.
- Published
- 2021
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36. Transgenic rice seeds expressing altered peptide ligands against the M3 muscarinic acetylcholine receptor suppress experimental sialadenitis-like Sjögren's syndrome.
- Author
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Kudo H, Tsuboi H, Asashima H, Takahashi H, Ono Y, Abe S, Honda F, Kondo Y, Wakasa Y, Takaiwa F, Takano M, Matsui M, Matsumoto I, and Sumida T
- Subjects
- Animals, Humans, Ligands, Mice, Oryza chemistry, Oryza genetics, Peptides administration & dosage, Peptides chemistry, Plants, Genetically Modified chemistry, Plants, Genetically Modified genetics, Protein Binding, Seeds chemistry, Sialadenitis immunology, Sjogren's Syndrome immunology, Spleen immunology, T-Lymphocytes, Regulatory immunology, Peptides therapeutic use, Plant Proteins chemistry, Receptor, Muscarinic M3 metabolism, Sialadenitis drug therapy, Sjogren's Syndrome drug therapy
- Abstract
Objective: We previously reported that Rag1
-/- mice inoculated with splenocytes from M3 muscarinic acetylcholine receptor (M3R) knockout mice immunized with an M3R peptide mixture developed sialadenitis-like Sjögren's syndrome (M3R-induced sialadenitis [MIS]). We also found that intravenous administration of altered peptide ligand (APL) of N-terminal 1 (N1), which is one of the T-cell epitopes of M3R, suppressed MIS. In this study, we aimed to evaluate the suppressive ability and its mechanisms of rice seeds expressing N1-APL7 against MIS. Methods: Rice seeds expressing N1 and N1-APL7 were orally administered to MIS mice for 2 weeks. The changes in saliva flow and sialadenitis (salivary gland inflammation) were analyzed. The M3R-specific T-cell response in the spleen and the expression of regulatory molecules in the cervical lymph nodes and mesenteric lymph nodes were also analyzed. Results: Oral administration of N1-APL7-expressing rice seeds significantly recovered reduction in saliva flow and suppressed sialadenitis when compared with treatment with nontransgenic rice seeds and N1 rice seeds. IFNγ production from M3R-reactive T cells tended to decline in the N1-APL7 rice-treated group as compared with those in the other groups. In the N1-APL7 rice-treated group, the mRNA expression levels of Foxp3 in the cervical-lymph-node CD4+ T cells were higher than those in the other groups. Conclusion: Oral administration of N1-APL7-expressing rice suppressed MIS via suppression of M3R-specific IFNγ and IL-17 production and via enhancement of regulatory molecule expression.Key messagesWe generated N1-peptide- or N1-APL7-expressing rice seeds. Oral administration of N1-APL7-expressing rice seeds significantly recovered the reduction of saliva flow and suppressed sialadenitis via the suppression of M3R specific IFNγ and IL-17 production and via enhancement of regulatory T (Treg) cells.- Published
- 2020
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37. M3 muscarinic acetylcholine receptor-reactive Th17 cells in primary Sjögren's syndrome.
- Author
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Abe S, Tsuboi H, Kudo H, Asashima H, Ono Y, Honda F, Takahashi H, Yagishita M, Hagiwara S, Kondo Y, Matsumoto I, and Sumida T
- Subjects
- Adult, Aged, Case-Control Studies, Epitopes, T-Lymphocyte immunology, Female, Follow-Up Studies, Humans, Male, Middle Aged, Prognosis, Receptor, Muscarinic M3 metabolism, Sjogren's Syndrome metabolism, Sjogren's Syndrome pathology, Autoantibodies immunology, Autoantigens immunology, Receptor, Muscarinic M3 immunology, Sjogren's Syndrome immunology, Th17 Cells immunology
- Abstract
M3 muscarinic acetylcholine receptor (M3R) is one of the autoantigens associated with Sjögren's syndrome (SS) and is localized in exocrine glands where disease-specific inflammation occurs. The inflammatory lesion is characterized by infiltration of CD4+ T cells, including clonally expanded Th17 cells. We undertook this study to identify circulating M3R-specific Th17 cells and to determine functional properties of those cells. Using the enzyme-linked immunospot assay (ELISpot) method, we identified M3R-reactive Th17 cells in the peripheral blood of patients with primary SS (pSS). Among 10 examined pSS patients, 10 healthy subjects (HS), and 5 IgG4-related disease (IgG4-RD) patients, M3R-reactive IL-17 secreting cells were significantly increased in 5 pSS patients specifically. The most common T cell epitope, which was analyzed and confirmed by coculture of isolated CD4+ T cells with antigen presenting cells plus M3R peptides in vitro, was peptide 83-95 of M3R. Peptide recognition was partly in an HLA-DR-restricted manner, confirmed by blocking assay. M3R-reactive Th17 cells positivity correlated with higher titers of anti-M3R antibodies, whose systemic disease activity score tended to be higher. Our studies highlight the role of tissue-specific autoantigen-derived circulating Th17 cells in pSS, for which further work might lead to antigen-specific targeted therapy.
- Published
- 2020
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38. Upregulation and pathogenic roles of CCL18-CCR8 axis in IgG4-related disease.
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Tsuboi H, Iizuka-Koga M, Asashima H, Takahashi H, Kudo H, Ono Y, Honda F, Iizuka A, Segawa S, Abe S, Yagishita M, Yokosawa M, Kondo Y, Moriyama M, Matsumoto I, Nakamura S, and Sumida T
- Subjects
- Adult, Chemokines, CC metabolism, Female, Humans, Immunoglobulin G4-Related Disease blood, Leukocytes metabolism, Male, Middle Aged, Receptors, CCR8 metabolism, Salivary Glands, Minor metabolism, Up-Regulation, Chemokines, CC blood, Immunoglobulin G4-Related Disease metabolism, Receptors, CCR8 blood
- Abstract
Objectives: To determine the protein expression level, expressing cell types, and pathogenic roles of chemokine (C-C motif) ligand 18 (CCL18) and its receptor chemokine (C-C motif) receptor 8 (CCR8) in affected tissues of patients with IgG4-related disease (IgG4-RD). Methods: The protein expression levels of CCL18 in labial salivary glands (LSGs) assessed by immunofluorescence (IF) staining were compared among patients with IgG4-RD ( n = 3), primary Sjögren's syndrome (pSS; n = 4), and control subjects ( n = 5). CCL18 expression levels in macrophages, CD11c
+ cells, B cells, and plasmacytes in LSGs were examined by double IF staining. The protein expression levels of CCR8 and expressing cells (T, B cells, and plasmacytes) in LSGs were also compared among patients with IgG4-RD, pSS, and control subjects by double IF staining. The effects of the CCL18-CCR8 axis on total IgG, IgG2, and IgG4 production by peripheral blood mononuclear cells (PBMCs) stimulated with CD40L, IL-4, IL-10, and IL-21 were examined by in vitro assays. Results: CCL18 was specifically upregulated in LSGs of patients with IgG4-RD, compared with only a few cells in pSS patients and none of the controls. The numbers of CCL18-producing macrophages, CD11c+ cells, and plasmacytes in LSGs were significantly higher in IgG4-RD patients than in pSS patients and control ( p < .05, each). Many T and B cells and some plasmacytes expressed CCR8 in LSGs of IgG4-RD and pSS patients. CCL18 specifically enhanced IgG4 production by stimulated PBMCs. Conclusion: CCL18-CCR8 axis was upregulated in LSGs of patients with IgG4-RD, suggesting possible roles of this axis in the pathogenesis of IgG4-RD.Key messagesThe CCL18-CCR8 axis in labial salivary glands (LSGs) and lacrimal glands of IgG4-RD patients was specifically upregulated compared with primary Sjögren's syndrome and control subjects.This axis might be a potentially novel therapeutic target in IgG4-RD, based on its important etiopathogenic roles, such as chemotaxis of various cells, induction of fibrosis, and enhancement of IgG4 production.- Published
- 2020
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39. RORγt antagonist improves Sjögren's syndrome-like sialadenitis through downregulation of CD25.
- Author
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Ono Y, Tsuboi H, Moriyama M, Asashima H, Kudo H, Takahashi H, Honda F, Abe S, Kondo Y, Takahashi S, Matsumoto I, Nakamura S, and Sumida T
- Subjects
- Animals, CD4-Positive T-Lymphocytes immunology, Down-Regulation, Humans, Mice, Mice, Transgenic, Salivary Glands, Aminopyridines therapeutic use, Interleukin-2 Receptor alpha Subunit genetics, Nuclear Receptor Subfamily 1, Group F, Member 3 antagonists & inhibitors, Sialadenitis drug therapy, Sjogren's Syndrome drug therapy, Sulfonamides therapeutic use
- Abstract
Objective: We reported previously that T-cell-specific RORγt-transgenic mice under human CD2 promoter (RORγt-Tg mice) developed severe spontaneous Sjögren's syndrome (SS)-like sialadenitis, induced by RORγt-overexpressing CD4
+ T cells and reduced regulatory T cells. The purpose of this study was to clarify the effectiveness and mechanisms of action of A213, a RORγt antagonist, in RORγt-Tg mice with SS-like sialadenitis., Methods: Six-week-old RORγt-Tg mice were administered orally of A213 or phosphate-buffered saline every 3 days for 2 weeks. We analyzed saliva volume, histopathology of salivary glands, populations of T cells in splenocytes and cervical lymph nodes (cLNs), and the protein expression levels of CD69 on CD4+ CD25+ Foxp3- and CD4+ CD25+ Foxp3+ cells in cLNs. We also investigated in vitro the potential immunomechanisms of action of A213., Results: A213 significantly increased saliva volume, reduced mononuclear cell infiltration in salivary glands, and reduced the focus score of sialadenitis. Analysis of the immunomechanisms using cLNs showed A213 significantly reduced the proportion of CD4+ CD25+ /CD4+ T cells and the protein expression levels of CD69 on CD4+ CD25+ Foxp3- cells. In vitro experiments showed that A213 suppressed CD25 expression on CD4+ T cells and reduced IL-2 production from CD4+ T cells derived from RORγt-Tg mice., Conclusion: A213 improves SS-like sialadenitis through the inhibition of CD4+ CD25+ cells in cLNs., (© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd. All rights reserved.)- Published
- 2020
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40. Renal Sarcoidosis With Multiple Organ Involvement.
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Shimizu M, Asashima H, Terasaki M, Toko H, Honda F, Ohyama A, Yagishita M, Takahashi H, Hagiwara S, Kondo Y, Tsuboi H, Matsumoto I, and Sumida T
- Subjects
- Female, Humans, Kidney Diseases etiology, Lung Diseases, Interstitial drug therapy, Lung Diseases, Interstitial etiology, Middle Aged, Sarcoidosis complications, Sarcoidosis drug therapy, Adrenal Cortex Hormones therapeutic use, Lung Diseases, Interstitial diagnostic imaging, Sarcoidosis diagnostic imaging
- Published
- 2020
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41. Association of anti-cyclic citrullinated peptide antibody with clinical features in patients with psoriatic arthritis.
- Author
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Hagiwara S, Tsuboi H, Terasaki T, Terasaki M, Toko H, Shimizu M, Honda F, Yagishita M, Ohyama A, Takahashi H, Yokosawa M, Asashima H, Kondo Y, Matsumoto I, and Sumida T
- Subjects
- Adult, Aged, Antirheumatic Agents therapeutic use, Arthritis, Psoriatic drug therapy, Arthritis, Psoriatic pathology, Biomarkers blood, Drug Resistance, Female, Humans, Male, Middle Aged, Tumor Necrosis Factor-alpha antagonists & inhibitors, Anti-Citrullinated Protein Antibodies blood, Arthritis, Psoriatic blood
- Abstract
Background: Although anti-cyclic citrullinated peptide antibody (anti-CCP Ab) is reported to be found in 5-20% of patients with psoriatic arthritis (PsA), its clinical significance has not been elucidated. Objective: To clarify the association of anti-CCP Ab with clinical features in PsA. Methods: Patients were enrolled who fulfilled the classification criteria for psoriatic arthritis (CASPAR) criteria and visited our hospital. We retrospectively compared clinical characteristics between those who were positive and negative for anti-CCP Ab and further compared changes in disease activity in the patients treated with biological disease-modifying anti-rheumatic drugs (DMARDs). Results: We examined 41 patients (11 females), seven were anti-CCP Ab-positive and 34 were negative. Age (55.0 ± 15.1 years old) and frequency of lung involvements (71.4%) in the anti-CCP Ab-positive group were significantly higher than those (40.0 ± 16.0 and 0%, respectively) in the negative group ( p < .05). Rheumatoid factor (RF) titer (749.4 ± 860.7 U/mL) and MMP-3 (604.8 ± 1060.6) in the anti-CCP Ab-positive group was significantly higher than that (3.6 ± 4.4 U/mL and 111.2 ± 77.4, respectively) in the negative group ( p < .05). Five patients were treated with tumor necrosis factor (TNF) inhibitors (infliximab (IFX): 3 and adalimumab (ADA): 2) in the anti-CCP Ab-positive group, while in the negative group there were 11 (IFX: 6, ADA: 4, and etanercept (ETN): 1). Within 6 months of treatment, arthritis did not improve with TNF inhibitors in the anti-CCP Ab-positive group, whereas it improved significantly in the negative group. Conclusion: In patients with PsA, anti-CCP Ab might be related to lung involvements, elderly onset, RF and MMP-3 titers, and resistance to TNF inhibitor.
- Published
- 2020
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42. Contrast Enhanced Computed Tomography Revealed Gallbladder Hemorrhage Due to Active Vasculitis in a Patient With Microscopic Polyangiitis.
- Author
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Honda F, Tsuboi H, Toko H, Terasaki T, Terasaki M, Shimizu M, Ohyama A, Yagishita M, Takahashi H, Yokosawa M, Asashima H, Hagiwara S, Kondo Y, Matsumoto I, and Sumida T
- Subjects
- Abdominal Pain diagnosis, Abdominal Pain etiology, Adrenal Cortex Hormones therapeutic use, Aged, Biopsy, Needle, Emergency Treatment, Gallbladder Diseases diagnostic imaging, Gallbladder Diseases etiology, Hemorrhage diagnostic imaging, Hemorrhage etiology, Humans, Immunohistochemistry, Male, Microscopic Polyangiitis diagnosis, Microscopic Polyangiitis drug therapy, Prognosis, Rare Diseases, Severity of Illness Index, Treatment Outcome, Cholecystectomy, Laparoscopic methods, Contrast Media, Gallbladder Diseases surgery, Hemorrhage surgery, Microscopic Polyangiitis complications, Tomography, X-Ray Computed methods
- Published
- 2019
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43. Effect of Biological Disease-modifying Anti-rheumatic Drugs on Airway and Interstitial Lung Disease in Patients with Rheumatoid Arthritis.
- Author
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Kurata I, Tsuboi H, Terasaki M, Shimizu M, Toko H, Honda F, Ohyama A, Yagishita M, Osada A, Ebe H, Kawaguchi H, Takahashi H, Hagiwara S, Asashima H, Kondo Y, Matsumoto I, and Sumida T
- Subjects
- Abatacept therapeutic use, Aged, Antibodies, Monoclonal, Humanized therapeutic use, Antirheumatic Agents administration & dosage, Antirheumatic Agents adverse effects, Arthritis, Rheumatoid physiopathology, Disease Progression, Female, Humans, Male, Middle Aged, Prognosis, Retrospective Studies, Risk Factors, Tomography, X-Ray Computed, Tumor Necrosis Factor-alpha therapeutic use, Antirheumatic Agents therapeutic use, Arthritis, Rheumatoid drug therapy, Arthritis, Rheumatoid epidemiology, Lung Diseases, Interstitial epidemiology, Lung Diseases, Interstitial physiopathology
- Abstract
Objective Biological disease-modifying anti-rheumatic drugs (bDMARDs) represent an important advance in alleviating rheumatoid arthritis (RA), but their effect on rheumatic airway disease (AD) and interstitial lung disease (ILD) is still unclear. This study was performed to evaluate the association of the use of different bDMARDs with new-onset or worsening of RA-AD/ILD. Methods We performed a retrospective cohort study of RA patients who received bDMARDs and assessed their AD/ILD before and after drug initiation in our hospital over the past 10 years. We evaluated the serial changes in computed tomography (CT), classified patients according to AD/ILD progression, and analyzed associations between clinical characteristics and outcomes. Results We enrolled 49 patients. Thirty patients received tumor necrosis factor inhibitors (TNFis), 12 received abatacept (ABT), and the remaining 7 received tocilizumab (TCZ). Seventeen patients had ILD, 10 had AD, and 6 had both AD and ILD before the initiation of bDMARDs. New emergence or exacerbation of AD/ILD was observed in 18 patients after drug initiation, while the remaining 31 remained stable or improved. Multiple logistic regression analyses revealed that pre-existing AD was an independent risk factor against the emergence or exacerbation of RA-AD/ILD, and ABT use was a protective factor against it. Conclusion Our study showed that pre-existing RA-AD is associated with future worsening of RA-AD/ILD, and ABT over other bDMARDs was associated with a better prognosis. Future studies to confirm our results are needed.
- Published
- 2019
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44. Associations between maternal clinical features and fetal outcomes in pregnancies of mothers with connective tissue diseases.
- Author
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Ohyama A, Tsuboi H, Noma H, Terasaki M, Shimizu M, Toko H, Honda F, Yagishita M, Takahashi H, Asashima H, Hagiwara S, Kondo Y, Matsumoto I, and Sumida T
- Subjects
- Adult, Female, Humans, Japan epidemiology, Pregnancy, Pregnancy Outcome epidemiology, Prognosis, Retrospective Studies, Risk Factors, Symptom Flare Up, Abortion, Spontaneous epidemiology, Abortion, Spontaneous etiology, Autoantibodies blood, Autoantibodies classification, Connective Tissue Diseases diagnosis, Connective Tissue Diseases epidemiology, Connective Tissue Diseases immunology, Connective Tissue Diseases therapy, Glucocorticoids therapeutic use, Pregnancy Complications diagnosis, Pregnancy Complications epidemiology, Pregnancy Complications immunology, Pregnancy Complications therapy
- Abstract
Objectives: The purpose of this study is to clarify associations between maternal clinical features and adverse pregnancy outcomes (APOs) in mothers with connective tissue diseases (CTDs)., Methods: We retrospectively examined maternal clinical features including backgrounds, autoantibodies, CTD flare-ups, and therapies during pregnancies as well as fetal outcomes in 90 pregnancies (66 mothers) at our hospital from January 2006 to September 2016., Results: Underlying CTDs were SLE (N = 41), MCTD (N = 10), RA (N = 15), SS (N = 10), and others (N = 14). Anti-SS-A antibody was detected in 60.3%, lupus anticoagulant (LAC) was in 11.4%, and anti-cardiolipin-β2glycoprotein1 antibody was in 18.5%. Flare-ups of CTDs occurred in 20 pregnancies (22.2%). Corticosteroids (CS) was administered in 73 pregnancies, immunosuppressants in four, and biologics in one. Among the 85 pregnancies other than five early abortions within 12 weeks of gestational age, 33 cases had APOs while the remaining 52 cases were normal. Although disease duration, MCTD, high dose of CS, flare-ups of CTDs, and positive LAC significantly correlated with APOs by univariate analysis, only MCTD was a significant independent predictor for APOs by multivariate analysis., Conclusion: Disease duration, MCTD, high dose of CS, flare-ups of CTDs, and LAC might be possible predictive risk factors for APOs in pregnancies with CTDs. Of these, MCTD was a significant independent risk factor.
- Published
- 2019
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45. Intractable Hemophagocytic Syndrome Associated with Systemic Lupus Erythematosus Resistant to Corticosteroids and Intravenous Cyclophosphamide That Was Successfully Treated with Cyclosporine A.
- Author
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Toko H, Tsuboi H, Umeda N, Honda F, Ohyama A, Takahashi H, Abe S, Yokosawa M, Asashima H, Hagiwara S, Hirota T, Kondo Y, Matsumoto I, and Sumida T
- Subjects
- Administration, Intravenous, Adrenal Cortex Hormones therapeutic use, Cyclophosphamide therapeutic use, Dermatologic Agents therapeutic use, Humans, Lupus Vasculitis, Central Nervous System drug therapy, Male, Methylprednisolone therapeutic use, Young Adult, Cyclosporine therapeutic use, Immunosuppressive Agents therapeutic use, Lupus Vasculitis, Central Nervous System complications, Lymphohistiocytosis, Hemophagocytic complications, Lymphohistiocytosis, Hemophagocytic drug therapy
- Abstract
Hemophagocytic syndrome (HPS) associated with systemic lupus erythematosus (SLE), dubbed acute lupus hemophagocytic syndrome (ALHS), is an intractable complication of SLE. A 24-year-old man who had been diagnosed with SLE three months previously, presented with fever, rash, hallucination, and pancytopenia accompanied with hyperferritinemia and bone marrow hemophagocytosis. He was diagnosed with ALHS and neuropsychiatric (NP)-SLE. Although 4 courses of methylprednisolone pulse therapy and 1 course of intravenous cyclophosphamide (IVCY) improved his NP-SLE, his ALHS did not respond. However, the addition of cyclosporine A (CsA) led to a rapid remission from ALHS. This suggests the usefulness of CsA in the treatment of intractable, corticosteroid- and IVCY-resistant ALHS.
- Published
- 2018
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46. Clinically Amyopathic Dermatomyositis with Interstitial Pneumonia That Was Successfully Treated with Plasma Exchange.
- Author
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Yagishita M, Kondo Y, Terasaki T, Terasaki M, Shimizu M, Honda F, Oyama A, Takahashi H, Yokosawa M, Asashima H, Hagiwara S, Tsuboi H, Matsumoto I, and Sumida T
- Subjects
- Humans, Male, Middle Aged, Dermatomyositis complications, Dermatomyositis therapy, Lung Diseases, Interstitial classification, Lung Diseases, Interstitial therapy, Plasma Exchange methods
- Abstract
Patients with clinically amyopathic dermatomyositis (CADM), a subset of dermatomyositis characterized by a lack of muscle involvement, frequently develop rapidly progressive and treatment-resistant interstitial lung disease. We report the case of a 49-year-old man who was diagnosed with CADM. He developed interstitial pneumonia, which did not respond to combination therapy with methylprednisolone pulse therapy, cyclophosphamide, and cyclosporine. We therefore attempted plasma exchange. After 7 courses of therapeutic plasma exchange, the interstitial pneumonia gradually improved. This case suggests that plasma exchange might be an effective therapeutic option for patients with progressive interstitial lung disease in steroid- and immunosuppressive therapy-refractive CADM.
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- 2018
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47. Clinical practice guideline for Sjögren's syndrome 2017.
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Sumida T, Azuma N, Moriyama M, Takahashi H, Asashima H, Honda F, Abe S, Ono Y, Hirota T, Hirata S, Tanaka Y, Shimizu T, Nakamura H, Kawakami A, Sano H, Ogawa Y, Tsubota K, Ryo K, Saito I, Tanaka A, Nakamura S, Takamura E, Tanaka M, Suzuki K, Takeuchi T, Yamakawa N, Mimori T, Ohta A, Nishiyama S, Yoshihara T, Suzuki Y, Kawano M, Tomiita M, and Tsuboi H
- Subjects
- Disease Management, Humans, Japan, Sjogren's Syndrome therapy, Practice Guidelines as Topic, Practice Patterns, Physicians' standards, Sjogren's Syndrome diagnosis
- Abstract
Objectives: The objective of this study is to develop clinical practice guideline (CPG) for Sjögren's syndrome (SS) based on recently available clinical and therapeutic evidences., Methods: The CPG committee for SS was organized by the Research Team for Autoimmune Diseases, Research Program for Intractable Disease of the Ministry of Health, Labor and Welfare (MHLW), Japan. The committee completed a systematic review of evidences for several clinical questions and developed CPG for SS 2017 according to the procedure proposed by the Medical Information Network Distribution Service (Minds). The recommendations and their strength were checked by the modified Delphi method. The CPG for SS 2017 has been officially approved by both Japan College of Rheumatology and the Japanese Society for SS., Results: The CPG committee set 38 clinical questions for clinical symptoms, signs, treatment, and management of SS in pediatric, adult and pregnant patients, using the PICO (P: patients, problem, population, I: interventions, C: comparisons, controls, comparators, O: outcomes) format. A summary of evidence, development of recommendation, recommendation, and strength for these 38 clinical questions are presented in the CPG., Conclusion: The CPG for SS 2017 should contribute to improvement and standardization of diagnosis and treatment of SS.
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- 2018
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48. Severe Adult-onset Still Disease with Constrictive Pericarditis and Pleuritis That Was Successfully Treated with Tocilizumab in Addition to Corticosteroids and Cyclosporin A.
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Kawaguchi H, Tsuboi H, Yagishita M, Terasaki T, Terasaki M, Shimizu M, Honda F, Ohyama A, Takahashi H, Miki H, Yokosawa M, Asashima H, Hagiwara S, Kondo Y, Matsumoto I, and Sumida T
- Subjects
- Adult, Asian People, Humans, Male, Pericarditis, Constrictive etiology, Pleurisy etiology, Treatment Outcome, Adrenal Cortex Hormones therapeutic use, Antibodies, Monoclonal, Humanized therapeutic use, Antirheumatic Agents therapeutic use, Cyclosporine therapeutic use, Pericarditis, Constrictive drug therapy, Pleurisy drug therapy, Still's Disease, Adult-Onset complications, Still's Disease, Adult-Onset drug therapy
- Abstract
Adult-onset Still disease (AOSD) is a systemic inflammatory disease characterized by fever, arthritis and rash. Corticosteroids represent a promising therapeutic option for AOSD; however, some resistant cases require immunosuppressants and biologic agents. We herein report the case of a 29-year-old Japanese man with severe AOSD, accompanied by constrictive pericarditis (CP) and pleuritis. Although 2 courses of steroid pulse and subsequent high-dose of prednisolone and cyclosporine A improved the patient's CP and pleuritis, his fever and inflammatory responses persisted. Tocilizumab (TCZ) was added to his treatment, which resulted in a rapid remission. This case suggests the usefulness of TCZ in the treatment of severe AOSD with CP and pleuritis.
- Published
- 2018
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49. Diffusion-weighted magnetic resonance imaging of parotid glands before and after abatacept therapy in patients with Sjögren's syndrome associated with rheumatoid arthritis: Utility to evaluate and predict response to treatment.
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Takahashi H, Tsuboi H, Yokosawa M, Asashima H, Hirota T, Kondo Y, Matsumoto I, and Sumida T
- Subjects
- Adult, Aged, Arthritis, Rheumatoid drug therapy, Arthritis, Rheumatoid pathology, Female, Humans, Magnetic Resonance Imaging standards, Middle Aged, Parotid Gland pathology, Sensitivity and Specificity, Sjogren's Syndrome complications, Sjogren's Syndrome drug therapy, Abatacept therapeutic use, Antirheumatic Agents therapeutic use, Arthritis, Rheumatoid diagnostic imaging, Magnetic Resonance Imaging methods, Parotid Gland diagnostic imaging, Sjogren's Syndrome diagnostic imaging
- Abstract
Objective: To compare parotid diffusion-weighted images (DWIs) taken before and after abatacept therapy in patients with Sjögren's syndrome (SS) associated with rheumatoid arthritis (RA) and to examine the utility in evaluation and prediction of response to therapy., Methods: DWIs of the parotid glands taken at baseline and 52 weeks after initiation of abatacept were analyzed in nine SS patients with RA using relative standard deviation (RSD) of the entire glands and signal intensity ratio (SIR) within the residual parenchyma. The correlation between changes in RSD and SIR and changes in salivary secretion based on Saxon's test was examined. Furthermore, baseline characteristics were compared in patients with increased and decreased salivary secretion after treatment. The predictive power of the parameter at baseline was examined using receiver operating characteristic (ROC) analysis., Results: Abatacept improved salivary secretion from 2076 ± 1535 at baseline to 2857 ± 1431 mg/2 min at 52 weeks (n = 9, p = .05). Increase of salivary secretion was significantly higher in patients with decreased RSD (n = 6) than increased RSD (n = 3) (1241 ± 713, -137 ± 142 mg/2 min, p = .02). The increase and decrease in RSD completely accorded with those of salivary secretion. Furthermore, SIR was the only parameter that was significantly different between patients with posttreatment increase and decrease in salivary secretion (p = .04). ROC analysis showed the sensitivity and specificity of SIR at baseline of ≥13.0 × 10
-2 for the prediction of the response to abatacept were 75.0% and 83.3%, respectively., Conclusions: Parotid DWI seems to be useful for evaluating and predicting the response in salivary secretion to abatacept in SS patients with RA.- Published
- 2018
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50. Recurrent Kikuchi-Fujimoto Disease Successfully Treated by the Concomitant Use of Hydroxychloroquine and Corticosteroids.
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Honda F, Tsuboi H, Toko H, Ohyama A, Takahashi H, Abe S, Yokosawa M, Asashima H, Hagiwara S, Hirota T, Kondo Y, Matsumoto I, and Sumida T
- Subjects
- Adult, Dose-Response Relationship, Drug, Drug Therapy, Combination, Female, Humans, Hydroxychloroquine administration & dosage, Immunosuppressive Agents administration & dosage, Prednisolone administration & dosage, Recurrence, Histiocytic Necrotizing Lymphadenitis drug therapy, Hydroxychloroquine therapeutic use, Immunosuppressive Agents therapeutic use, Prednisolone therapeutic use
- Abstract
Kikuchi-Fujimoto disease (KFD) is a benign disease of unknown etiology characterized by lymphadenopathy and a fever. For the majority of patients with KFD, the course is self-limited; however, the optimum method of managing recurrent cases has not yet been established. We herein report a case of a 42-year-old Japanese woman with KFD (confirmed by a lymph node biopsy). Although high-dose prednisolone (PSL) rapidly induced remission, she experienced four recurrences on treatment tapering. Concomitant use of hydroxychloroquine (HCQ) with low-dose PSL induced continuous remission. This is the first case to suggest the effectiveness of HCQ for recurrent KFD in a Japanese patient.
- Published
- 2017
- Full Text
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