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Ueno N, Sugiyama Y, Kobayashi Y, Murakami Y, Iwama T, Sasaki T, Kunogi T, Sakatani A, Takahashi K, Tanaka K, Serikawa S, Ando K, Kashima S, Muto M, Inaba Y, Moriichi K, Tanabe H, Okumura T, Fujiya M. Concomitant pharmacologic medications influence the clinical outcomes of granulocyte and monocyte adsorptive apheresis in patients with ulcerative colitis: A multicenter retrospective cohort study. J Clin Apher 2023. [PMID: 36636880 DOI: 10.1002/jca.22040] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/22/2022] [Revised: 09/20/2022] [Accepted: 12/27/2022] [Indexed: 01/14/2023]
Abstract
BACKGROUND Granulocyte and monocyte adsorptive apheresis (GMA) with Adacolumn has been used as a remission induction therapy for patients with active ulcerative colitis (UC). Herein, we investigated the influence of concomitant medications in the remission induction of GMA in patients with active UC. METHODS This multicenter retrospective cohort study included patients with UC underwent GMA in five independent institutions in Japan from January 2011 to July 2021. Factors including concomitant medications associated with clinical remission (CR) were analyzed statistically. RESULT A total of 133 patients were included. Seventy-four patients achieved a CR after GMA. The multivariable analysis revealed that concomitant medication with 5-aminosalicylic acid, Mayo endoscopic subscore (MES), and concomitant medication with immunosuppressors (IMs) remained as predictors of CR after GMA. In the subgroup analysis in patients with MES of 2, concomitant medication with IMs was demonstrated as a significant negative factor of CR after GMA (P = .042, OR 0.354). Seventy-four patients who achieved CR after GMA were followed up for 52 weeks. In the multivariable analysis, the maintenance therapy with IMs was demonstrated as a significant positive factor of sustained CR up to 52 weeks (P = .038, OR 2.214). Furthermore, the rate of sustained CR in patients with biologics and IMs was significantly higher than that in patients with biologics only (P = .002). CONCLUSION GMA was more effective for patients with active UC that relapsed under treatment without IMs. Furthermore, the addition of IMs should be considered in patients on maintenance therapy with biologics after GMA.
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Affiliation(s)
- Nobuhiro Ueno
- Division of Metabolism and Biosystemic Science, Gastroenterology, and Hematology/Oncology, Department of Medicine, Asahikawa Medical University, Asahikawa, Hokkaido, Japan
| | - Yuya Sugiyama
- Division of Metabolism and Biosystemic Science, Gastroenterology, and Hematology/Oncology, Department of Medicine, Asahikawa Medical University, Asahikawa, Hokkaido, Japan
| | - Yu Kobayashi
- Division of Metabolism and Biosystemic Science, Gastroenterology, and Hematology/Oncology, Department of Medicine, Asahikawa Medical University, Asahikawa, Hokkaido, Japan
| | - Yuki Murakami
- Division of Metabolism and Biosystemic Science, Gastroenterology, and Hematology/Oncology, Department of Medicine, Asahikawa Medical University, Asahikawa, Hokkaido, Japan
| | - Takuya Iwama
- Asahikawa City Hospital, Asahikawa, Hokkaido, Japan
| | - Takahiro Sasaki
- Division of Metabolism and Biosystemic Science, Gastroenterology, and Hematology/Oncology, Department of Medicine, Asahikawa Medical University, Asahikawa, Hokkaido, Japan
| | - Takehito Kunogi
- Division of Metabolism and Biosystemic Science, Gastroenterology, and Hematology/Oncology, Department of Medicine, Asahikawa Medical University, Asahikawa, Hokkaido, Japan
| | - Aki Sakatani
- Division of Metabolism and Biosystemic Science, Gastroenterology, and Hematology/Oncology, Department of Medicine, Asahikawa Medical University, Asahikawa, Hokkaido, Japan
| | - Keitaro Takahashi
- Division of Metabolism and Biosystemic Science, Gastroenterology, and Hematology/Oncology, Department of Medicine, Asahikawa Medical University, Asahikawa, Hokkaido, Japan
| | - Kazuyuki Tanaka
- Asahikawa Kosei General Hospital, Asahikawa, Hokkaido, Japan
| | | | - Katsuyoshi Ando
- Division of Metabolism and Biosystemic Science, Gastroenterology, and Hematology/Oncology, Department of Medicine, Asahikawa Medical University, Asahikawa, Hokkaido, Japan
| | - Shin Kashima
- Division of Metabolism and Biosystemic Science, Gastroenterology, and Hematology/Oncology, Department of Medicine, Asahikawa Medical University, Asahikawa, Hokkaido, Japan
| | | | - Yuhei Inaba
- Asahikawa City Hospital, Asahikawa, Hokkaido, Japan
| | - Kentaro Moriichi
- Division of Metabolism and Biosystemic Science, Gastroenterology, and Hematology/Oncology, Department of Medicine, Asahikawa Medical University, Asahikawa, Hokkaido, Japan
| | - Hiroki Tanabe
- Division of Metabolism and Biosystemic Science, Gastroenterology, and Hematology/Oncology, Department of Medicine, Asahikawa Medical University, Asahikawa, Hokkaido, Japan
| | - Toshikatsu Okumura
- Division of Metabolism and Biosystemic Science, Gastroenterology, and Hematology/Oncology, Department of Medicine, Asahikawa Medical University, Asahikawa, Hokkaido, Japan
| | - Mikihiro Fujiya
- Division of Metabolism and Biosystemic Science, Gastroenterology, and Hematology/Oncology, Department of Medicine, Asahikawa Medical University, Asahikawa, Hokkaido, Japan
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Tsuzuki Y, Shiomi R, Matsumoto H, Miyaguchi K, Kusano T, Ohgo H, Nakamoto H, Imaeda H. Combined effects of granulocyte and monocyte adsorption apheresis and corticosteroids on ulcerative colitis. J Clin Biochem Nutr 2023; 72:68-73. [PMID: 36777077 PMCID: PMC9899916 DOI: 10.3164/jcbn.22-52] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/11/2022] [Accepted: 07/26/2022] [Indexed: 11/06/2022] Open
Abstract
Several new treatments for ulcerative colitis have been developed recently. The depletion of leukocytes by granulocyte and monocyte adsorption apheresis (GMA) was developed and adapted for patients with ulcerative colitis with rare adverse events. We investigated whether treatment with GMA and prednisolone (GMA + PSL) is more effective than PSL alone for patients with moderate to severe ulcerative colitis. Forty-seven patients with moderate to severe ulcerative colitis were retrospectively analyzed. Among the 47 patients, 27 received PSL, while 20 received GMA + PSL. The clinical activity of ulcerative colitis was evaluated using the Lichtiger clinical activity index (CAI) and serum levels of C-reactive protein. Mayo endoscopic score (MES) was used to examine endoscopic activity. The clinical remission rate was significantly higher in the GMA + PSL group than in the PSL group (65% vs 29.6%, p = 0.0206). The mucosal healing rate was also significantly higher in the GMA + PSL group than in the PSL group (60% vs 26%, p = 0.0343). The combination of GMA and steroids may be more effective than steroids alone for inducing clinical remission and mucosal healing in patients with moderate to severe ulcerative colitis.
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Affiliation(s)
- Yoshikazu Tsuzuki
- Department of Gastroenterology, Saitama Medical University, 38 Morohongo, Moroyama-machi, Iruma-gun, Saitama 350-0495, Japan
- Department of General Internal Medicine, Saitama Medical University, 38 Morohongo, Moroyama-machi, Iruma-gun, Saitama 350-0495, Japan
| | - Rie Shiomi
- Department of General Internal Medicine, Saitama Medical University, 38 Morohongo, Moroyama-machi, Iruma-gun, Saitama 350-0495, Japan
| | - Hisashi Matsumoto
- Department of General Internal Medicine, Saitama Medical University, 38 Morohongo, Moroyama-machi, Iruma-gun, Saitama 350-0495, Japan
| | - Kazuya Miyaguchi
- Department of General Internal Medicine, Saitama Medical University, 38 Morohongo, Moroyama-machi, Iruma-gun, Saitama 350-0495, Japan
| | - Takeru Kusano
- Department of General Internal Medicine, Saitama Medical University, 38 Morohongo, Moroyama-machi, Iruma-gun, Saitama 350-0495, Japan
| | - Hideki Ohgo
- Department of Gastroenterology, Saitama Medical University, 38 Morohongo, Moroyama-machi, Iruma-gun, Saitama 350-0495, Japan
- Department of General Internal Medicine, Saitama Medical University, 38 Morohongo, Moroyama-machi, Iruma-gun, Saitama 350-0495, Japan
| | - Hidetomo Nakamoto
- Department of General Internal Medicine, Saitama Medical University, 38 Morohongo, Moroyama-machi, Iruma-gun, Saitama 350-0495, Japan
| | - Hiroyuki Imaeda
- Department of Gastroenterology, Saitama Medical University, 38 Morohongo, Moroyama-machi, Iruma-gun, Saitama 350-0495, Japan
- Department of General Internal Medicine, Saitama Medical University, 38 Morohongo, Moroyama-machi, Iruma-gun, Saitama 350-0495, Japan
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Dai YC, Qiao D, Fang CY, Chen QQ, Que RY, Xiao TG, Zheng L, Wang LJ, Zhang YL. Single-cell RNA-sequencing combined with bulk RNA-sequencing analysis of peripheral blood reveals the characteristics and key immune cell genes of ulcerative colitis. World J Clin Cases 2022; 10:12116-12135. [PMID: 36483809 PMCID: PMC9724533 DOI: 10.12998/wjcc.v10.i33.12116] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/26/2022] [Revised: 09/27/2022] [Accepted: 10/27/2022] [Indexed: 11/22/2022] Open
Abstract
BACKGROUND Ulcerative colitis (UC) is a complicated disease caused by the interaction between genetic and environmental factors that affects mucosal homeostasis and triggers an inappropriate immune response. Single-cell RNA sequencing (scRNA-seq) can be used to rapidly obtain the precise gene expression patterns of thousands of cells in the intestine, analyze the characteristics of cells with the same phenotype, and provide new insights into the growth and development of intestinal organs, the clonal evolution of cells, and immune cell changes. These findings can provide new ideas for the diagnosis and treatment of intestinal diseases. AIM To identify clinical phenotypes and biomarkers that can predict the response of UC patients to specific therapeutic drugs and thus aid the diagnosis and treatment of UC. METHODS Using the Gene Expression Omnibus (GEO) database, we analyzed peripheral blood cell subtypes of patients with UC by scRNA-seq combined with bulk RNA sequencing (RNA-seq) to reveal the core genes of UC. We then combined weighted gene correlation network analysis (WGCNA) and least absolute shrinkage and selection operator (LASSO) analysis to reveal diagnostic markers of UC. RESULTS After processing the scRNA-seq data, we obtained data from approximately 24340 cells and identified 17 cell types. Through intercellular communication analysis, we selected monocyte marker genes as the candidate gene set for the prediction model. Construction of a WGCNA coexpression network identified RhoB, cathepsin D (CTSD) and zyxin (ZYX) as core genes. Immune infiltration analysis showed that these three core genes were strongly correlated with immune cells. Functional enrichment analysis showed that the differentially expressed genes were closely related to immune and inflammatory responses, which are associated with many challenges in the diagnosis and treatment of UC. CONCLUSION Through scRNA-seq analysis, LASSO diagnostic model building and WGCNA, we identified RhoB, CTSD and ZYX as core genes of UC that are closely related to monocyte infiltration that may serve as diagnostic markers and molecular targets for UC therapeutic intervention.
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Affiliation(s)
- Yan-Cheng Dai
- Department of Gastroenterology, Shanghai Traditional Chinese Medicine-Integrated Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200082, China
| | - Dan Qiao
- Department of Gastroenterology, Shanghai Traditional Chinese Medicine-Integrated Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200082, China
| | - Chen-Ye Fang
- Department of Gastroenterology, Traditional Chinese Medicine Hospital of Ningbo, Ningbo 315000, Zhejiang Province, China
| | - Qiu-Qin Chen
- Department of Pathology, Shanghai Traditional Chinese Medicine-Integrated Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200082, China
| | - Ren-Ye Que
- Department of Gastroenterology, Shanghai Traditional Chinese Medicine-Integrated Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200082, China
| | - Tie-Gang Xiao
- Department of Gastroenterology, Shanghai Traditional Chinese Medicine-Integrated Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200082, China
| | - Lie Zheng
- Department of Gastroenterology, Traditional Chinese Medicine Hospital of Xi’an 730000, Shaanxi Province, China
| | - Li-Juan Wang
- Experimental Education Center, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China
| | - Ya-Li Zhang
- Institute of Digestive Diseases, LongHua Hospital Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China
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Bamias G, Zampeli E, Domènech E. Targeting neutrophils in inflammatory bowel disease: revisiting the role of adsorptive granulocyte and monocyte apheresis. Expert Rev Gastroenterol Hepatol 2022; 16:721-735. [PMID: 35833363 DOI: 10.1080/17474124.2022.2100759] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/04/2022] [Accepted: 07/08/2022] [Indexed: 11/09/2022]
Abstract
INTRODUCTION Inflammatory bowel disease (IBD) is a chronic immune-mediated disease of the gastrointestinal tract comprising Crohn's disease (CD) and ulcerative colitis (UC). While any part of the digestive tract can be affected in CD, mucosal inflammation in UC is limited to the colon. Differences and similarities between the two conditions are reflected by their pathophysiology. AREAS COVERED An overview of immunological aspects, pharmacological management, and biomarkers of IBD is provided. The role of adsorptive granulocyte and monocyte apheresis (GMA) is reviewed including its primary and secondary effects on the immune system, as well as clinical studies in IBD (mainly UC), and potential biomarkers for adsorptive GMA. EXPERT OPINION In UC, adsorptive GMA with Adacolumn (Adacolumn®, JIMRO Co., Ltd. Takasaki, Gunma, Japan) selectively depletes elevated myeloid lineage leukocytes and has a range of beneficial secondary immune effects. Adsorptive GMA is a safe and effective non-pharmacological treatment option for UC. Pilot studies have reported promising results for adsorptive GMA in combination with biological agents, although larger studies are required. Fecal calprotectin concentrations, neutrophil counts in histological samples and/or the neutrophil/lymphocyte ratio in peripheral blood may prove to be useful biomarkers for predicting GMA effectiveness in the future.
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Affiliation(s)
- Giorgos Bamias
- GI-Unit, 3rd Department of Internal Medicine National and Kapodistrian University of Athens, Sotiria Hospital, Athens, Greece
| | - Evanthia Zampeli
- Gastroenterology Department, Alexandra General Hospital, Athens, Greece
| | - Eugeni Domènech
- Gastroenterology Department, Hospital Universitari Germans Trias I Pujol, Badalona, Catalonia, Spain, and Centro de Investigación Biomédica En Red de Enfermedades Hepáticas Y Digestivas (CIBEREHD), Madrid, Spain
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Yamaguchi Y, Nakagawa M, Nakagawa S, Nagao K, Inoue S, Sugiyama T, Izawa S, Hijikata Y, Ebi M, Funaki Y, Ogasawara N, Sasaki M, Kasugai K. Rapidly Progressing Aseptic Abscesses in a Patient with Ulcerative Colitis. Intern Med 2021; 60:725-730. [PMID: 32999240 PMCID: PMC7990631 DOI: 10.2169/internalmedicine.5733-20] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/19/2023] Open
Abstract
Aseptic abscesses (AAs) are extraintestinal manifestations of inflammatory bowel disease (IBD). IBD-associated AAs are rare in Japan. We treated a 45-year-old man with ulcerative colitis (UC)-associated AAs. During remission, multiple progressive abscesses were detected in the spleen; he underwent splenectomy because an infectious disease was suspected. Although his condition improved temporarily after splenectomy, a large liver abscess was noted, and a diagnosis of UC-associated AAs was made. Granulocytapheresis (GCAP) and infliximab (IFX) administration resolved the abscess. This is the first reported case of UC-associated AAs in a Japanese patient treated by splenectomy, GCAP, and IFX.
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Affiliation(s)
- Yoshiharu Yamaguchi
- Department of Gastroenterology, Aichi Medical University School of Medicine, Japan
| | - Marie Nakagawa
- Department of Gastroenterology, Aichi Medical University School of Medicine, Japan
| | - Shoko Nakagawa
- Department of Gastroenterology, Aichi Medical University School of Medicine, Japan
| | - Kazuhiro Nagao
- Department of Gastroenterology, Aichi Medical University School of Medicine, Japan
| | - Satoshi Inoue
- Department of Gastroenterology, Aichi Medical University School of Medicine, Japan
| | - Tomoya Sugiyama
- Department of Gastroenterology, Aichi Medical University School of Medicine, Japan
| | - Shinya Izawa
- Department of Gastroenterology, Aichi Medical University School of Medicine, Japan
| | - Yasutaka Hijikata
- Department of Gastroenterology, Aichi Medical University School of Medicine, Japan
| | - Masahide Ebi
- Department of Gastroenterology, Aichi Medical University School of Medicine, Japan
| | - Yasushi Funaki
- Department of Gastroenterology, Aichi Medical University School of Medicine, Japan
| | - Naotaka Ogasawara
- Department of Gastroenterology, Aichi Medical University School of Medicine, Japan
| | - Makoto Sasaki
- Department of Gastroenterology, Aichi Medical University School of Medicine, Japan
| | - Kunio Kasugai
- Department of Gastroenterology, Aichi Medical University School of Medicine, Japan
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