Cell-free concentrated ascites reinfusion therapy enables removal of extracellular vesicles and circulating immune complexes in ascites
Yu Yamaji
Department of Internal Medicine and Rheumatology, Juntendo University School of Medicine, Tokyo, Japan
Search for more papers by this authorCorresponding Author
Goh Murayama
Department of Internal Medicine and Rheumatology, Juntendo University School of Medicine, Tokyo, Japan
Correspondence
Goh Murayama, Department of Internal Medicine and Rheumatology, Juntendo University School of Medicine Graduate School of Medicine, 1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, Japan.
Email: [email protected]
Search for more papers by this authorMoeko Inoue
Department of Internal Medicine and Rheumatology, Juntendo University School of Medicine, Tokyo, Japan
Search for more papers by this authorTakuya Urita
Clinical Engineering Department, Juntendo University Hospital, Tokyo, Japan
Search for more papers by this authorTakashi Hirayama
Department of Obstetrics and Gynecology, Faculty of Medicine, Juntendo University School of Medicine, Tokyo, Japan
Search for more papers by this authorAkira Uchiyama
Department of Gastroenterology, Juntendo University School of Medicine, Tokyo, Japan
Search for more papers by this authorMasaki Nojima
Department of Internal Medicine and Rheumatology, Juntendo University School of Medicine, Tokyo, Japan
Search for more papers by this authorYukitomo Hagiwara
Department of Internal Medicine and Rheumatology, Juntendo University School of Medicine, Tokyo, Japan
Search for more papers by this authorTakumi Saito
Department of Internal Medicine and Rheumatology, Juntendo University School of Medicine, Tokyo, Japan
Search for more papers by this authorTaiga Kuga
Department of Internal Medicine and Rheumatology, Juntendo University School of Medicine, Tokyo, Japan
Search for more papers by this authorTomoko Miyashita
Department of Internal Medicine and Rheumatology, Juntendo University School of Medicine, Tokyo, Japan
Search for more papers by this authorMakio Kusaoi
Department of Internal Medicine and Rheumatology, Juntendo University School of Medicine, Tokyo, Japan
Search for more papers by this authorYasuhisa Terao
Department of Obstetrics and Gynecology, Faculty of Medicine, Juntendo University School of Medicine, Tokyo, Japan
Search for more papers by this authorAtsuo Itakura
Department of Obstetrics and Gynecology, Faculty of Medicine, Juntendo University School of Medicine, Tokyo, Japan
Search for more papers by this authorKenichi Ikejima
Department of Gastroenterology, Juntendo University School of Medicine, Tokyo, Japan
Search for more papers by this authorNaoto Tamura
Department of Internal Medicine and Rheumatology, Juntendo University School of Medicine, Tokyo, Japan
Search for more papers by this authorKen Yamaji
Department of Internal Medicine and Rheumatology, Juntendo University School of Medicine, Tokyo, Japan
Search for more papers by this authorYu Yamaji
Department of Internal Medicine and Rheumatology, Juntendo University School of Medicine, Tokyo, Japan
Search for more papers by this authorCorresponding Author
Goh Murayama
Department of Internal Medicine and Rheumatology, Juntendo University School of Medicine, Tokyo, Japan
Correspondence
Goh Murayama, Department of Internal Medicine and Rheumatology, Juntendo University School of Medicine Graduate School of Medicine, 1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, Japan.
Email: [email protected]
Search for more papers by this authorMoeko Inoue
Department of Internal Medicine and Rheumatology, Juntendo University School of Medicine, Tokyo, Japan
Search for more papers by this authorTakuya Urita
Clinical Engineering Department, Juntendo University Hospital, Tokyo, Japan
Search for more papers by this authorTakashi Hirayama
Department of Obstetrics and Gynecology, Faculty of Medicine, Juntendo University School of Medicine, Tokyo, Japan
Search for more papers by this authorAkira Uchiyama
Department of Gastroenterology, Juntendo University School of Medicine, Tokyo, Japan
Search for more papers by this authorMasaki Nojima
Department of Internal Medicine and Rheumatology, Juntendo University School of Medicine, Tokyo, Japan
Search for more papers by this authorYukitomo Hagiwara
Department of Internal Medicine and Rheumatology, Juntendo University School of Medicine, Tokyo, Japan
Search for more papers by this authorTakumi Saito
Department of Internal Medicine and Rheumatology, Juntendo University School of Medicine, Tokyo, Japan
Search for more papers by this authorTaiga Kuga
Department of Internal Medicine and Rheumatology, Juntendo University School of Medicine, Tokyo, Japan
Search for more papers by this authorTomoko Miyashita
Department of Internal Medicine and Rheumatology, Juntendo University School of Medicine, Tokyo, Japan
Search for more papers by this authorMakio Kusaoi
Department of Internal Medicine and Rheumatology, Juntendo University School of Medicine, Tokyo, Japan
Search for more papers by this authorYasuhisa Terao
Department of Obstetrics and Gynecology, Faculty of Medicine, Juntendo University School of Medicine, Tokyo, Japan
Search for more papers by this authorAtsuo Itakura
Department of Obstetrics and Gynecology, Faculty of Medicine, Juntendo University School of Medicine, Tokyo, Japan
Search for more papers by this authorKenichi Ikejima
Department of Gastroenterology, Juntendo University School of Medicine, Tokyo, Japan
Search for more papers by this authorNaoto Tamura
Department of Internal Medicine and Rheumatology, Juntendo University School of Medicine, Tokyo, Japan
Search for more papers by this authorKen Yamaji
Department of Internal Medicine and Rheumatology, Juntendo University School of Medicine, Tokyo, Japan
Search for more papers by this authorAbstract
Introduction
Cell-free and concentrated ascites reinfusion therapy (CART) is used for ascites in decompensated cirrhosis and malignant tumors. We investigated extracellular vesicles (EVs) and circulating immune complexes (CICs) as potential inflammatory inducers in ascites and verified whether they can be removed through CART treatment.
Methods
Ascites from 10 patients, including those with cancer, undergoing CART were analyzed. We compared the inflammatory inducers in untreated ascites, ascites processed using AHF-MO (conventional CART filter), and those filtered with EC20W (double-filtration plasmapheresis filter). A cell-based reporter assay measured biological activity.
Results
AHF-MO significantly lowered EV and CIC levels along with physiological activity in the treated ascites. EC20W was superior in terms of EV removal but showed no significant difference from AHF-MO in CIC removal. AHF-MO showed a greater reduction in physiological activity.
Conclusion
The CART process with AHF-MO effectively removes EVs and CICs, reducing physiological activity and demonstrating its safety in ascites treatment.
CONFLICT OF INTEREST STATEMENT
The authors declare no competing interests.
Open Research
DATA AVAILABILITY STATEMENT
All data necessary to evaluate the conclusions of this study are provided. Additional data or methods related to this study can be obtained by contacting the authors if required.
Supporting Information
Filename | Description |
---|---|
tap70022-sup-0001-supinfo.docxWord 2007 document , 51.1 KB | Data S1 Supporting Information. |
Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
REFERENCES
- 1Ito T, Hanafusa N, Iwase S, Noiri E, Nangaku M, Nakagawa K, et al. Effects of cell-free and concentrated ascites reinfusion therapy (CART) on symptom relief of malignancy-related ascites. Int J Clin Oncol. 2015; 20(3): 623–628.
- 2Yamada Y, Inui K, Hara Y, Fuji K, Sonoda K, Hashimoto K, et al. Verification of serum albumin elevating effect of cell-free and concentrated ascites reinfusion therapy for ascites patients: a retrospective controlled cohort study. Sci Rep. 2019; 9(1):10195. https://doi.org/10.1038/s41598-019-46774-9
- 3Orimi S, Mizuno K, Narahara M, Umakosi H, Kaihara M, Hashimoto M. A study of appropriate flow rate settings for cell-free and concentrated ascites reinfusion therapy and change of cytokine concentrations in ascites. Ther Apher Dial. 2011; 15(4): 411–414.
- 4Beck S, Hochreiter B, Schmid JA. Extracellular vesicles linking inflammation, cancer and thrombotic risks. Front Cell Dev Biol. 2022; 10:859863.
- 5Hoshino A, Costa-Silva B, Shen TL, Rodrigues G, Hashimoto A, Tesic Mark M, et al. Tumour exosome integrins determine organotropic metastasis. Nature. 2015; 527(7578): 329–335.
- 6Natsui K, Tsuchiya A, Imamiya R, Osada-Oka M, Ishii Y, Koseki Y, et al. Escherichia coli-derived outer-membrane vesicles induce immune activation and progression of cirrhosis in mice and humans. Liver Int. 2023; 43(5): 1126–1140.
- 7Kolb P, Giese S, Voll RE, Hengel H, Falcone V. Immune complexes as culprits of immunopathology in severe COVID-19. Med Microbiol Immunol. 2023; 212(2): 185–191. https://doi.org/10.1007/s00430-022-00743-8
- 8Sansonno D, Dammacco F. Hepatitis C virus, cryoglobulinaemia, and vasculitis: immune complex relations. Lancet Infect Dis. 2005; 5(4): 227–236. https://doi.org/10.1016/S1473-3099(05)70053-0
- 9Connelly-Smith L, Alquist CR, Aqui NA, Hofmann JC, Klingel R, Onwuemene OA, et al. Guidelines on the use of therapeutic apheresis in clinical practice – evidence-based approach from the Writing Committee of the American Society for Apheresis: the ninth special issue. J Clin Apher. 2023; 38(2): 77–278. https://doi.org/10.1002/jca.22043
- 10Saito T, Takatsuji R, Murayama G, Yamaji Y, Hagiwara Y, Nishioka Y, et al. Double-filtration plasmapheresis reduces type I interferon bioavailability and inducing activity in systemic lupus erythematosus. Immunol Med. 2024; 47(4): 264–274. https://doi.org/10.1080/25785826.2024.2372918
- 11Runyon BA, Montano AA, Akriviadis EA, Antillon MR, Irving MA, McHutchison JG. The serum-ascites albumin gradient is superior to the exudate-transudate concept in the differential diagnosis of ascites. Ann Intern Med. 1992; 117(3): 215–220.
- 12Tsuchiya S, Yamabe M, Yamaguchi Y, Kobayashi Y, Konno T, Tada K. Establishment and characterization of a human acute monocytic leukemia cell line (THP-1). Int J Cancer. 1980; 26(2): 171–176. https://doi.org/10.1002/ijc.2910260208
- 13Kalluri R. The biology and function of exosomes in cancer. J Clin Invest. 2016; 126(4): 1208–1215. https://doi.org/10.1172/JCI81135
- 14Bebelman MP, Smit MJ, Pegtel DM, Baglio SR. Biogenesis and function of extracellular vesicles in cancer. Pharmacol Ther. 2018; 188: 1–11. https://doi.org/10.1016/j.pharmthera.2018.02.013
- 15Nawaz M, Fatima F, Nazarenko I, Ekström K, Murtaza I, Anees M, et al. Extracellular vesicles in ovarian cancer: applications to tumor biology, immunotherapy and biomarker discovery. Expert Rev Proteomics. 2016; 13(4): 395–409. https://doi.org/10.1586/14789450.2016.1165613
- 16Jeppesen DK, Zhang Q, Franklin JL, Coffey RJ. Extracellular vesicles and nanoparticles: emerging complexities. Trends Cell Biol. 2023; 33(8): 667–681. https://doi.org/10.1016/j.tcb.2023.01.002
- 17Gottschalk TA, Tsantikos E, Hibbs ML. Pathogenic inflammation and its therapeutic targeting in systemic lupus erythematosus. Front Immunol. 2015; 6: 550. https://doi.org/10.3389/fimmu.2015.00550 eCollection 2015.
- 18Cramer DW, O'Rourke DJ, Vitonis AF, Matulonis UA, Dijohnson DA, Sluss PM, et al. CA125 immune complexes in ovarian cancer patients with low CA125 concentrations. Clin Chem. 2010; 56(12): 1889–1892. https://doi.org/10.1373/clinchem.2010.153122
- 19Oldstone MB. Immune complexes in cancer: demonstration of complexes in mice bearing neuroblastomas. J Natl Cancer Inst. 1975; 54(1): 223–228. https://doi.org/10.1093/jnci/54.1.223
- 20Namisaki T, Tsuji Y, Kitade M, Yorioka N, Fujinaga Y, Sawada Y, et al. Endotoxin activity reflects an increase in body temperature in cirrhotic patients with ascites undergoing cell-free and concentrated ascites reinfusion therapy. In Vivo. 2022; 36(3): 1477–1484. https://doi.org/10.21873/invivo.12854
- 21Ohara T, Setsuhara C, Nakao S, Noguchi Y, Shimazu K, Komura K, et al. Investigation of endotoxin positivity in ascites at the time of cell-free and concentrated ascites re-infusion therapy. Intern Med. 2023; 62(21): 3119–3123. https://doi.org/10.2169/internalmedicine.0994-22
- 22Ito T, Hanafusa N, Iwase S, Noiri E, Nangaku M, Nakagawa K, et al. Ascitic IL-10 concentration predicts prognosis of patients undergoing cell-free and concentrated ascites reinfusion therapy. Ther Apher Dial. 2020; 24(1): 90–95. https://doi.org/10.1111/1744-9987.12863
- 23Kaps L, Medina-Montano C, Bros M, Grabbe S, Gairing SJ, Schleicher EM, et al. Comparison of inflammatory cytokine levels in hepatic and jugular veins of patients with cirrhosis. Mediat Inflamm. 2023; 2023:9930902. https://doi.org/10.1155/2023/9930902
- 24Nakajima F, Shibahara N, Oka H, Sakaguchi M, Amemoto K, Ueda H, et al. Relationship between IL-6 levels and fever during ascites reinfusion therapy (in Japanese). J Jpn Soc Dial Ther. 2001; 34(5): 335–338.
10.4009/jsdt.34.335 Google Scholar
- 25Iwanaszko M, Kimmel M. NF-κB and IRF pathways: cross-regulation on target genes promoter level. BMC Genomics. 2015; 16(1): 307. https://doi.org/10.1186/s12864-015-1511-7
- 26Tsubokura M, Adegawa Y, Kojima M, Tanosaki R, Ohtake R, Kase Y, et al. Adverse effects of cell-free and concentrated ascites reinfusion therapy for malignant ascites: a single-institute experience. BMC Cancer. 2022; 22(1): 268. https://doi.org/10.1186/s12885-022-09298-6