{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T00:48:11Z","timestamp":1760143691309,"version":"build-2065373602"},"reference-count":59,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2024,2,23]],"date-time":"2024-02-23T00:00:00Z","timestamp":1708646400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Asahi Kasei Medical Co., Ltd."}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Immunoadsorption (IA) has proven to be clinically effective in the treatment of steroid-refractory multiple sclerosis (MS) relapses, but its mechanism of action remains unclear. We used miniaturized adsorber devices with a tryptophan-immobilized polyvinyl alcohol (PVA) gel sorbent to mimic the IA treatment of patients with MS in vitro. The plasma was screened before and after adsorption with regard to disease-specific mediators, and the effect of the IA treatment on the migration of neutrophils and the integrity of the endothelial cell barrier was tested in cell-based models. The in vitro IA treatment with miniaturized adsorbers resulted in reduced plasma levels of cytokines and chemokines. We also found a reduced migration of neutrophils towards patient plasma treated with the adsorbers. Furthermore, the IA-treated plasma had a positive effect on the endothelial cell barrier\u2019s integrity in the cell culture model. Our findings suggest that IA results in a reduced infiltration of cells into the central nervous system by reducing leukocyte transmigration and preventing blood\u2013brain barrier breakdown. This novel approach of performing in vitro blood purification therapies on actual patient samples with miniaturized adsorbers and testing their effects in cell-based assays that investigate specific hypotheses of the pathophysiology provides a promising platform for elucidating the mechanisms of action of those therapies in various diseases.<\/jats:p>","DOI":"10.3390\/ijms25052590","type":"journal-article","created":{"date-parts":[[2024,2,23]],"date-time":"2024-02-23T04:31:23Z","timestamp":1708662683000},"page":"2590","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["The Utility of Miniaturized Adsorbers in Exploring the Cellular and Molecular Effects of Blood Purification: A Pilot Study with a Focus on Immunoadsorption in Multiple Sclerosis"],"prefix":"10.3390","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6574-1753","authenticated-orcid":false,"given":"Andreas","family":"K\u00f6rtge","sequence":"first","affiliation":[{"name":"Department of Extracorporeal Therapy Systems, Fraunhofer Institute for Cell Therapy and Immunology IZI, 18057 Rostock, Germany"},{"name":"Division of Nephrology, Center for Internal Medicine, Rostock University Medical Center, 18057 Rostock, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anne","family":"Breitr\u00fcck","sequence":"additional","affiliation":[{"name":"Department of Extracorporeal Therapy Systems, Fraunhofer Institute for Cell Therapy and Immunology IZI, 18057 Rostock, Germany"},{"name":"Division of Nephrology, Center for Internal Medicine, Rostock University Medical Center, 18057 Rostock, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sandra","family":"Do\u00df","sequence":"additional","affiliation":[{"name":"Department of Extracorporeal Therapy Systems, Fraunhofer Institute for Cell Therapy and Immunology IZI, 18057 Rostock, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jacqueline","family":"Hofrichter","sequence":"additional","affiliation":[{"name":"Department of Extracorporeal Therapy Systems, Fraunhofer Institute for Cell Therapy and Immunology IZI, 18057 Rostock, Germany"},{"name":"Division of Nephrology, Center for Internal Medicine, Rostock University Medical Center, 18057 Rostock, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sophie-Charlotte","family":"Nelz","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Center for Internal Medicine, Rostock University Medical Center, 18057 Rostock, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Horst","family":"Kr\u00fcsemann","sequence":"additional","affiliation":[{"name":"Department of Extracorporeal Therapy Systems, Fraunhofer Institute for Cell Therapy and Immunology IZI, 18057 Rostock, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Reinhold","family":"Wasserkort","sequence":"additional","affiliation":[{"name":"Department of Extracorporeal Therapy Systems, Fraunhofer Institute for Cell Therapy and Immunology IZI, 18057 Rostock, Germany"},{"name":"Division of Nephrology, Center for Internal Medicine, Rostock University Medical Center, 18057 Rostock, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Brit","family":"Fitzner","sequence":"additional","affiliation":[{"name":"Division of Neuroimmunology, Department of Neurology, Rostock University Medical Center, 18147 Rostock, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7015-3094","authenticated-orcid":false,"given":"Michael","family":"Hecker","sequence":"additional","affiliation":[{"name":"Division of Neuroimmunology, Department of Neurology, Rostock University Medical Center, 18147 Rostock, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Steffen","family":"Mitzner","sequence":"additional","affiliation":[{"name":"Department of Extracorporeal Therapy Systems, Fraunhofer Institute for Cell Therapy and Immunology IZI, 18057 Rostock, Germany"},{"name":"Division of Nephrology, Center for Internal Medicine, Rostock University Medical Center, 18057 Rostock, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Uwe Klaus","family":"Zettl","sequence":"additional","affiliation":[{"name":"Division of Neuroimmunology, Department of Neurology, Rostock University Medical Center, 18147 Rostock, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,2,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"905","DOI":"10.1038\/s41573-019-0035-2","article-title":"Progressive multiple sclerosis: From pathophysiology to therapeutic strategies","volume":"18","author":"Faissner","year":"2019","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_2","unstructured":"Goodin, D.S. (2014). Handbook of Clinical Neurology: Multiple Sclerosis and Related Disorders, Elsevier."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1111\/ene.13819","article-title":"Multiple sclerosis\u2014A review","volume":"26","author":"Dobson","year":"2019","journal-title":"Eur. J. Neurol."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Hecker, M., B\u00fchring, J., Fitzner, B., Rommer, P.S., and Zettl, U.K. (2021). Genetic, Environmental and Lifestyle Determinants of Accelerated Telomere Attrition as Contributors to Risk and Severity of Multiple Sclerosis. Biomolecules, 11.","DOI":"10.3390\/biom11101510"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"507","DOI":"10.1038\/nrn3275","article-title":"Will the real multiple sclerosis please stand up?","volume":"13","author":"Stys","year":"2012","journal-title":"Nat. Rev. Neurosci."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"3770","DOI":"10.1016\/j.febslet.2011.04.066","article-title":"How do immune cells overcome the blood-brain barrier in multiple sclerosis?","volume":"585","author":"Larochelle","year":"2011","journal-title":"FEBS Lett."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"300","DOI":"10.1159\/000447059","article-title":"Escalation Therapy of Steroid Refractory Multiple Sclerosis Relapse with Tryptophan Immunoadsorption\u2014Observational Multicenter Study with 147 Patients","volume":"75","author":"Schimrigk","year":"2016","journal-title":"Eur. Neurol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1186\/1742-2094-9-80","article-title":"Immunoadsorption therapy in patients with multiple sclerosis with steroid-refractory optical neuritis","volume":"9","author":"Koziolek","year":"2012","journal-title":"J. Neuroinflamm."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"381","DOI":"10.1002\/jca.21686","article-title":"Immunoadsorption or plasma exchange in steroid-refractory multiple sclerosis and neuromyelitis optica","volume":"34","author":"Lipphardt","year":"2019","journal-title":"J. Clin. Apher."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1002\/jca.10034","article-title":"Development of an in vitro miniature model to simulate immunoadsorption in patients with systemic lupus erythematosus","volume":"17","author":"Avenhaus","year":"2002","journal-title":"J. Clin. Apher."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"865","DOI":"10.1136\/jnnp.52.7.865","article-title":"IgG immunoadsorption in experimental allergic neuritis: Effect on antibody levels and clinical course","volume":"52","author":"Harvey","year":"1989","journal-title":"J. Neurol. Neurosurg. Psychiatry"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"440","DOI":"10.1111\/j.1365-2249.1990.tb05468.x","article-title":"Extracorporeal immunoadsorption therapy on rats. In vivo depletion of specific antibodies","volume":"82","author":"Nilsson","year":"1990","journal-title":"Clin. Exp. Immunol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1026","DOI":"10.3389\/fnins.2019.01026","article-title":"Cerebrospinal Fluid and Blood Cytokines as Biomarkers for Multiple Sclerosis: A Systematic Review and Meta-Analysis of 226 Studies with 13,526 Multiple Sclerosis Patients","volume":"13","author":"Bai","year":"2019","journal-title":"Front. Neurosci."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1013933","DOI":"10.3389\/fnmol.2022.1013933","article-title":"New insight into neurological degeneration: Inflammatory cytokines and blood-brain barrier","volume":"15","author":"Yang","year":"2022","journal-title":"Front. Mol. Neurosci."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"375","DOI":"10.1007\/s11011-020-00648-6","article-title":"A comprehensive review on the role of chemokines in the pathogenesis of multiple sclerosis","volume":"36","author":"Honarmand","year":"2021","journal-title":"Metab. Brain Dis."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1016\/j.cyto.2015.01.030","article-title":"Interleukin 12 (IL-12) family cytokines: Role in immune pathogenesis and treatment of CNS autoimmune disease","volume":"75","author":"Sun","year":"2015","journal-title":"Cytokine"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1689","DOI":"10.1586\/1744666X.2014.973856","article-title":"Interleukin-15 in the treatment of cancer","volume":"10","author":"Waldmann","year":"2014","journal-title":"Expert Rev. Clin. Immunol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"4119","DOI":"10.4049\/jimmunol.1100885","article-title":"B cell-derived IL-15 enhances CD8 T cell cytotoxicity and is increased in multiple sclerosis patients","volume":"187","author":"Schneider","year":"2011","journal-title":"J. Immunol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"5693","DOI":"10.4049\/jimmunol.1002188","article-title":"Contribution of astrocyte-derived IL-15 to CD8 T cell effector functions in multiple sclerosis","volume":"185","author":"Saikali","year":"2010","journal-title":"J. Immunol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1016\/j.cyto.2008.01.003","article-title":"Interleukin-15 improves cytotoxicity of natural killer cells via up-regulating NKG2D and cytotoxic effector molecule expression as well as STAT1 and ERK1\/2 phosphorylation","volume":"42","author":"Zhang","year":"2008","journal-title":"Cytokine"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1255","DOI":"10.1084\/jem.181.3.1255","article-title":"Chemoattraction of human blood T lymphocytes by interleukin-15","volume":"181","author":"Wilkinson","year":"1995","journal-title":"J. Exp. Med."},{"key":"ref_22","first-page":"626","article-title":"Cytokine-Defined B Cell Responses as Therapeutic Targets in Multiple Sclerosis","volume":"6","author":"Li","year":"2015","journal-title":"Front. Immunol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1016\/j.cytogfr.2018.10.004","article-title":"Pathological roles of the homeostatic chemokine CXCL12","volume":"44","author":"Janssens","year":"2018","journal-title":"Cytokine Growth Factor Rev."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1038\/cmi.2017.107","article-title":"The unique structural and functional features of CXCL12","volume":"15","author":"Janssens","year":"2018","journal-title":"Cell. Mol. Immunol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1189\/jlb.1003479","article-title":"Synergy between proinflammatory ligands of G protein-coupled receptors in neutrophil activation and migration","volume":"76","author":"Gouwy","year":"2004","journal-title":"J. Leukoc. Biol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1583","DOI":"10.1002\/eji.200425753","article-title":"Chemokines synergize in the recruitment of circulating neutrophils into inflamed tissue","volume":"35","author":"Struyf","year":"2005","journal-title":"Eur. J. Immunol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1059","DOI":"10.7150\/thno.44364","article-title":"CXCL12-mediated monocyte transmigration into brain perivascular space leads to neuroinflammation and memory deficit in neuropathic pain","volume":"11","author":"Mai","year":"2021","journal-title":"Theranostics"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1002\/jca.21953","article-title":"Immunoadsorption and plasma exchange-Efficient treatment options for neurological autoimmune diseases","volume":"37","author":"Boedecker","year":"2022","journal-title":"J. Clin. Apher."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"220","DOI":"10.1186\/s12974-022-02583-y","article-title":"Immunoadsorption versus double-dose methylprednisolone in refractory multiple sclerosis relapses","volume":"19","author":"Pfeuffer","year":"2022","journal-title":"J. Neuroinflamm."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"360","DOI":"10.1111\/1744-9987.12467","article-title":"Removal Characteristics of Immunoadsorption With the Immusorba TR-350 Column Using Conventional and Selective Plasma Separators","volume":"20","author":"Ohkubo","year":"2016","journal-title":"Ther. Apher. Dial."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1111\/1744-9987.12820","article-title":"Removal Characteristics of Immunoadsorption with the Tryptophan-Immobilized Column Using Conventional and Selective Plasma Separators in the Treatment of Myasthenia Gravis","volume":"23","author":"Ohkubo","year":"2019","journal-title":"Ther. Apher. Dial."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"671","DOI":"10.1016\/j.transci.2017.08.013","article-title":"Immunoadsorption in neurological disorders","volume":"56","author":"Oji","year":"2017","journal-title":"Transfus. Apher. Sci."},{"key":"ref_33","first-page":"31","article-title":"Modulation of immunity in patients with autoimmune disease and cancer treated by extracorporeal immunoadsorption with PROSORBA columns","volume":"26","author":"Snyder","year":"1989","journal-title":"Semin. Hematol."},{"key":"ref_34","first-page":"283","article-title":"Immunoadsorption and plasma exchange in multiple sclerosis: Complement and plasma protein behaviour","volume":"19","author":"Palm","year":"1991","journal-title":"Biomater. Artif. Cells Immobil. Biotechnol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"338","DOI":"10.1212\/WNL.45.2.338","article-title":"Treatment of myasthenia gravis by immunoadsorption of plasma","volume":"45","author":"Grob","year":"1995","journal-title":"Neurology"},{"key":"ref_36","first-page":"309","article-title":"Increase in Peripheral Blood Leukocytes and Chemokines During Immunoadsorbent Therapy","volume":"16","author":"Ota","year":"1997","journal-title":"Jpn. J. Apher."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1002\/(SICI)1098-1101(1998)13:4<167::AID-JCA5>3.0.CO;2-N","article-title":"Identification of complement activators and elucidation of the fate of complement activation products during extracorporeal plasma purification therapy","volume":"13","author":"Fadul","year":"1998","journal-title":"J. Clin. Apher."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1016\/S0955-3886(97)00098-2","article-title":"Immunological effects of therapeutic immunoadsorption with respect to biocompatibility","volume":"19","author":"Kadar","year":"1998","journal-title":"Transfus. Sci."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1067","DOI":"10.1046\/j.1525-1594.1998.06170.x","article-title":"Complement activation as a cause of transient hypotension during plasmapheresis","volume":"22","author":"Shiga","year":"1998","journal-title":"Artif. Organs"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1016\/j.transci.2004.07.014","article-title":"Immunoadsorption therapy and complement activation","volume":"32","author":"Lochman","year":"2005","journal-title":"Transfus. Apher. Sci."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1401","DOI":"10.1177\/1352458512438238","article-title":"Systemic complement profiling in multiple sclerosis as a biomarker of disease state","volume":"18","author":"Ingram","year":"2012","journal-title":"Mult. Scler."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1016\/S1473-0502(01)00038-6","article-title":"Is complement activation combined with antibody removal the mystery of successful immunoadsorption in multiple sclerosis?","volume":"24","author":"Schneidewind","year":"2001","journal-title":"Transfus. Apher. Sci."},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Balasa, R., Barcutean, L., Mosora, O., and Manu, D. (2021). Reviewing the Significance of Blood-Brain Barrier Disruption in Multiple Sclerosis Pathology and Treatment. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22168370"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"894","DOI":"10.1016\/j.stemcr.2017.02.021","article-title":"Establishment of a Human Blood-Brain Barrier Co-culture Model Mimicking the Neurovascular Unit Using Induced Pluri- and Multipotent Stem Cells","volume":"8","author":"Cubukova","year":"2017","journal-title":"Stem Cell Rep."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"765","DOI":"10.1001\/jama.2020.26858","article-title":"Diagnosis and Treatment of Multiple Sclerosis: A Review","volume":"325","author":"McGinley","year":"2021","journal-title":"JAMA"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1146\/annurev-pathol-052920-040318","article-title":"The Immune Response in Multiple Sclerosis","volume":"17","author":"Farez","year":"2022","journal-title":"Annu. Rev. Pathol."},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Nguyen, K., Juillard, P., Hawke, S., Grau, G.E., and Marsh-Wakefield, F. (2022). Trans-Endothelial Migration of Memory T Cells Is Impaired in Alemtuzumab-Treated Multiple Sclerosis Patients. J. Clin. Med., 11.","DOI":"10.3390\/jcm11216266"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"577392","DOI":"10.1016\/j.jneuroim.2020.577392","article-title":"Selective modulation of trans-endothelial migration of lymphocyte subsets in multiple sclerosis patients under fingolimod treatment","volume":"349","author":"Hawke","year":"2020","journal-title":"J. Neuroimmunol."},{"key":"ref_49","first-page":"1015","article-title":"Interferon-beta inhibits activated leukocyte migration through human brain microvascular endothelial cell monolayer","volume":"79","author":"Lou","year":"1999","journal-title":"Lab. Investig. J. Tech. Methods Pathol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1016\/S0165-5728(02)00098-X","article-title":"Interferon-beta directly influences monocyte infiltration into the central nervous system","volume":"127","author":"Floris","year":"2002","journal-title":"J. Neuroimmunol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1016\/j.jaut.2005.01.004","article-title":"Th1 and Th2 lymphocyte migration across the human BBB is specifically regulated by interferon beta and copolymer-1","volume":"24","author":"Prat","year":"2005","journal-title":"J. Autoimmun."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"310","DOI":"10.1191\/1352458505ms1184oa","article-title":"Elevated endothelial microparticle-monocyte complexes induced by multiple sclerosis plasma and the inhibitory effects of interferon-beta 1b on release of endothelial microparticles, formation and transendothelial migration of monocyte-endothelial microparticle complexes","volume":"11","author":"Jimenez","year":"2005","journal-title":"Mult. Scler."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1370","DOI":"10.1093\/brain\/awh163","article-title":"Multiple sclerosis: Glatiramer acetate inhibits monocyte reactivity in vitro and in vivo","volume":"127","author":"Weber","year":"2004","journal-title":"Brain"},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Zhao, Y., Chen, C., Xiao, X., Fang, L., Cheng, X., Chang, Y., Peng, F., Wang, J., Shen, S., and Wu, S. (2023). Teriflunomide Promotes Blood-Brain Barrier Integrity by Upregulating Claudin-1 via the Wnt\/\u03b2-catenin Signaling Pathway in Multiple Sclerosis. Mol. Neurobiol., 1\u201317.","DOI":"10.1007\/s12035-023-03655-7"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"2438","DOI":"10.4049\/jimmunol.1400401","article-title":"Neutrophils mediate blood-spinal cord barrier disruption in demyelinating neuroinflammatory diseases","volume":"193","author":"Chamma","year":"2014","journal-title":"J. Immunol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"965169","DOI":"10.3389\/fnagi.2022.965169","article-title":"The role of neutrophils in the dysfunction of central nervous system barriers","volume":"14","author":"Pietronigro","year":"2022","journal-title":"Front. Aging Neurosci."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1016\/j.jneuroim.2008.05.026","article-title":"Effect of IgG immunoadsorption on serum cytokines in MG and LEMS patients","volume":"201\u2013202","author":"Baggi","year":"2008","journal-title":"J. Neuroimmunol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"4160","DOI":"10.1038\/srep04160","article-title":"A retinoic acid-enhanced, multicellular human blood-brain barrier model derived from stem cell sources","volume":"4","author":"Lippmann","year":"2014","journal-title":"Sci. Rep."},{"key":"ref_59","first-page":"897","article-title":"Recommendation for the determination of the catalytic concentration of lactate dehydrogenase at 37 degrees C. Standardization Committee of the German Society for Clinical Chemistry, Enzyme Working Group of the German Society for Clinical Chemistry","volume":"31","author":"Lorentz","year":"1993","journal-title":"Eur. J. Clin. Chem. Clin. Biochem. J. Forum Eur. Clin. Chem. Soc."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/5\/2590\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T14:03:36Z","timestamp":1760105016000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/5\/2590"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,2,23]]},"references-count":59,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2024,3]]}},"alternative-id":["ijms25052590"],"URL":"https:\/\/doi.org\/10.3390\/ijms25052590","relation":{},"ISSN":["1422-0067"],"issn-type":[{"type":"electronic","value":"1422-0067"}],"subject":[],"published":{"date-parts":[[2024,2,23]]}}}