{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T09:47:39Z","timestamp":1785577659859,"version":"3.56.0"},"reference-count":49,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2020,6,27]],"date-time":"2020-06-27T00:00:00Z","timestamp":1593216000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000265","name":"Medical Research Council","doi-asserted-by":"publisher","award":["MR\/P008399\/1"],"award-info":[{"award-number":["MR\/P008399\/1"]}],"id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>The inflammatory neuropathies are disabling conditions with diverse immunological mechanisms. In some, a pathogenic role for immunoglobulin G (IgG)-class autoantibodies is increasingly appreciated, and immunoadsorption (IA) may therefore be a useful therapeutic option. We reviewed the use of and response to IA or plasma exchange (PLEx) in a cohort of 41 patients with nodal\/paranodal antibodies identified from a total of 573 individuals with suspected inflammatory neuropathies during the course of routine diagnostic testing (PNAb cohort). 20 patients had been treated with PLEx and 4 with IA. Following a global but subjective evaluation by their treating clinicians, none of these patients were judged to have had a good response to either of these treatment modalities. Sequential serology of one PNAb+ case suggests prolonged suppression of antibody levels with frequent apheresis cycles or adjuvant therapies, may be required for effective treatment. We further retrospectively evaluated the serological status of 40 patients with either Guillain-Barr\u00e9 syndrome (GBS) or chronic inflammatory demyelinating polyneuropathy (CIDP), and a control group of 20 patients with clinically-isolated syndrome\/multiple sclerosis (CIS\/MS), who had all been treated with IgG-depleting IA (IA cohort). 32 of these patients (8\/20 with CIDP, 13\/20 with GBS, 11\/20 with MS) were judged responsive to apheresis despite none of the serum samples from this cohort testing positive for IgG antibodies against glycolipids or nodal\/paranodal cell-adhesion molecules. Although negative on antigen specific assays, three patients\u2019 pre-treatment sera and eluates were reactive against different components of myelinating co-cultures. In summary, preliminary evidence suggests that GBS\/CIDP patients without detectable IgG antibodies on routine diagnostic tests may nevertheless benefit from IA, and that an unbiased screening approach using myelinating co-cultures may assist in the detection of further autoantibodies which remain to be identified in such patients.<\/jats:p>","DOI":"10.3390\/jcm9072025","type":"journal-article","created":{"date-parts":[[2020,6,30]],"date-time":"2020-06-30T14:24:24Z","timestamp":1593527064000},"page":"2025","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":34,"title":["Immunoadsorption and Plasma Exchange in Seropositive and Seronegative Immune-Mediated Neuropathies"],"prefix":"10.3390","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0072-1708","authenticated-orcid":false,"given":"Alexander J.","family":"Davies","sequence":"first","affiliation":[{"name":"Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford OX3 9DU, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janev","family":"Fehmi","sequence":"additional","affiliation":[{"name":"Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford OX3 9DU, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2737-7495","authenticated-orcid":false,"given":"Makbule","family":"Senel","sequence":"additional","affiliation":[{"name":"Department of Neurology, University of Ulm, 89081 Ulm, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hayrettin","family":"Tumani","sequence":"additional","affiliation":[{"name":"Department of Neurology, University of Ulm, 89081 Ulm, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johannes","family":"Dorst","sequence":"additional","affiliation":[{"name":"Department of Neurology, University of Ulm, 89081 Ulm, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2039-3457","authenticated-orcid":false,"given":"Simon","family":"Rinaldi","sequence":"additional","affiliation":[{"name":"Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford OX3 9DU, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,6,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"541","DOI":"10.1097\/WCO.0000000000000137","article-title":"Pathogenic mechanisms in inflammatory and paraproteinaemic peripheral neuropathies","volume":"27","author":"Rinaldi","year":"2014","journal-title":"Curr. Opin. Neurol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1111\/j.1085-9489.2005.0010202.x","article-title":"The immunobiology of Guillain-Barre syndromes","volume":"10","author":"Willison","year":"2005","journal-title":"J. Peripher. Nerv. Syst."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1136\/jnnp-2016-315480","article-title":"Nodes, paranodes and neuropathies","volume":"89","author":"Fehmi","year":"2017","journal-title":"J. Neurol. Neurosurg. Psychiatry"},{"key":"ref_4","first-page":"CD001798","article-title":"Plasma exchange for Guillain-Barr\u00e9 syndrome","volume":"2017","author":"Chevret","year":"2017","journal-title":"Cochrane Database Syst. Rev."},{"key":"ref_5","first-page":"CD003906","article-title":"Plasma exchange for chronic inflammatory demyelinating polyradiculoneuropathy","volume":"2015","author":"Mehndiratta","year":"2015","journal-title":"Cochrane Database Syst. Rev."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Eftimov, F., Winer, J.B., Vermeulen, M., De Haan, R., and Van Schaik, I.N. (2013). Intravenous immunoglobulin for chronic inflammatory demyelinating polyradiculoneuropathy. Cochrane Database Syst. Rev., CD001797.","DOI":"10.1002\/14651858.CD001797.pub3"},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Hughes, R.A.C., Rapha\u00ebl, J.C., Swan, A.V., and A Doorn, P. (2004). Intravenous immunoglobulin for Guillain-Barr\u00e9 syndrome. Cochrane Database Syst. Rev., CD002063.","DOI":"10.1002\/14651858.CD002063.pub2"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"486","DOI":"10.1002\/jca.21546","article-title":"A prospective study comparing tryptophan immunoadsorption with therapeutic plasma exchange for the treatment of chronic inflammatory demyelinating polyneuropathy","volume":"32","author":"Lieker","year":"2017","journal-title":"J. Clin. Apher."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1016\/j.transci.2005.07.010","article-title":"A pilot study to compare the use of the Excorim staphylococcal protein immunoadsorption system and IVIG in chronic inflammatory demyelinating polyneuropathy","volume":"33","author":"Zinman","year":"2005","journal-title":"Transfus. Apher. Sci."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"644","DOI":"10.1136\/jnnp.72.5.644","article-title":"Immunoadsorption inferior to plasma exchange in a patient with chronic inflammatory demyelinating polyradiculoneuropathy","volume":"72","author":"Hadden","year":"2002","journal-title":"J. Neurol. Neurosurg. Psychiatry"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1016\/S0955-3886(97)00100-8","article-title":"Chronic inflammatory demyelinating polyradiculoneuropathy: Superiority of protein A immunoadsorption over plasma exchange treatment","volume":"19","author":"Ullrich","year":"1998","journal-title":"Transfus. Sci."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1159\/000331011","article-title":"Immunoadsorption in Patients with Chronic Inflammatory Demyelinating Polyradiculoneuropathy with Unsatisfactory Response to First-Line Treatment","volume":"66","author":"Galldiks","year":"2011","journal-title":"Eur. Neurol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"348","DOI":"10.1111\/j.1744-9987.1997.tb00053.x","article-title":"Can immunoadsorption plasmapheresis be used as the first choice therapy for neuroimmunological disorders?","volume":"1","author":"Yamawaki","year":"1997","journal-title":"Ther. Apher."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"310","DOI":"10.1111\/j.1744-9987.2009.00730.x","article-title":"Guillain-Barr\u00e9 Syndrome Treated by Membrane Plasma Exchange and\/or Immunoadsorption","volume":"13","author":"Pernat","year":"2009","journal-title":"Ther. Apher. Dial."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"431","DOI":"10.1016\/j.braindev.2004.09.013","article-title":"Immunoadsorption therapy for a child with Guillain-Barre syndrome subsequent to Mycoplasma infection: A case study","volume":"27","author":"Arakawa","year":"2005","journal-title":"Brain Dev."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1111\/j.1526-0968.2004.00138.x","article-title":"Tryptophan-immobilized Column-based Immunoadsorption as the Choice Method for Plasmapheresis in Guillain-Barre Syndrome","volume":"8","author":"Okamiya","year":"2004","journal-title":"Ther. Apher. Dial."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1046\/j.1526-0968.2000.00183.x","article-title":"Immunoadsorption in Guillain-Barr\u00e9 syndrome and myasthenia gravis","volume":"4","author":"Haupt","year":"2000","journal-title":"Ther. Apher."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"340","DOI":"10.1111\/j.1744-9987.1997.tb00051.x","article-title":"Two Patients with Acute Guillain-Barr\u00e9 Syndrome Treated with Different Apheresis Methods","volume":"1","author":"Uetakagaito","year":"1997","journal-title":"Ther. Apher."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1016\/S0887-8994(98)00010-1","article-title":"Immunoadsorption Therapy in Guillain-Barr\u00e9 Syndrome","volume":"19","author":"Hirai","year":"1998","journal-title":"Pediatric  Neurol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1136\/jnnp.64.3.399","article-title":"Development of facial palsy during immunoadsorption plasmapheresis in Miller Fisher syndrome: A clinical report of two cases","volume":"64","author":"Chida","year":"1998","journal-title":"J. Neurol. Neurosurg. Psychiatry"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"574","DOI":"10.1002\/ana.410310522","article-title":"Treatment of Guillain-Barr\u00e9 syndrome with protein-A immunoadsorption: Report of two cases","volume":"31","author":"Ruiz","year":"1992","journal-title":"Ann. Neurol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"557","DOI":"10.1272\/jnms.69.557","article-title":"Plasma Immunoadsorption Therapy for Guillain-Barr\u00e9 Syndrome: Critical Day for Initiation","volume":"69","author":"Takei","year":"2002","journal-title":"J. Nippon. Med. Sch."},{"key":"ref_23","first-page":"CD003280","article-title":"Immunomodulatory treatment other than corticosteroids, immunoglobulin and plasma exchange for chronic inflammatory demyelinating polyradiculoneuropathy","volume":"2017","author":"Brassington","year":"2017","journal-title":"Cochrane Database Syst. Rev."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Rolfes, L., Pfeuffer, S., Ruck, T., Melzer, N., Pawlitzki, M., Heming, M., Brand, M., Wiendl, H., and Meuth, S. (2019). Ruck Therapeutic Apheresis in Acute Relapsing Multiple Sclerosis: Current Evidence and Unmet Needs\u2014A Systematic Review. J. Clin. Med., 8.","DOI":"10.3390\/jcm8101623"},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Lipphardt, M., Wallbach, M., and Koziolek, M.J. (2020). Plasma Exchange or Immunoadsorption in Demyelinating Diseases: A Meta-Analysis. J. Clin. Med., 9.","DOI":"10.3390\/jcm9051597"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"2591","DOI":"10.1093\/brain\/awf272","article-title":"Peripheral neuropathies and anti-glycolipid antibodies","volume":"125","author":"Willison","year":"2002","journal-title":"Brain"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1016\/S0022-510X(98)00067-7","article-title":"Ability to remove immunoglobulins and anti-ganglioside antibodies by plasma exchange, double-filtration plasmapheresis and immunoadsorption","volume":"157","author":"Tagawa","year":"1998","journal-title":"J. Neurol. Sci."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"2241","DOI":"10.1212\/WNL.0b013e31827689ad","article-title":"Neurofascin as a target for autoantibodies in peripheral neuropathies","volume":"79","author":"Ng","year":"2012","journal-title":"Neurology"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"370","DOI":"10.1002\/ana.23794","article-title":"Antibodies to contactin-1 in chronic inflammatory demyelinating polyneuropathy","volume":"73","author":"Querol","year":"2012","journal-title":"Ann. Neurol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"879","DOI":"10.1212\/WNL.0000000000000205","article-title":"Neurofascin IgG4 antibodies in CIDP associate with disabling tremor and poor response to IVIg","volume":"82","author":"Querol","year":"2014","journal-title":"Neurology"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"2617","DOI":"10.1093\/brain\/aww189","article-title":"Auto-antibodies to contactin-associated protein 1 (Caspr) in two patients with painful inflammatory neuropathy","volume":"139","author":"Doppler","year":"2016","journal-title":"Brain"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1851","DOI":"10.1093\/brain\/awx124","article-title":"Autoantibodies to nodal isoforms of neurofascin in chronic inflammatory demyelinating polyneuropathy","volume":"140","author":"Delmont","year":"2017","journal-title":"Brain"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"2906","DOI":"10.1007\/s00415-018-9082-6","article-title":"Short-term and long-term effects of immunoadsorption in refractory chronic inflammatory demyelinating polyneuropathy: A prospective study in 17 patients","volume":"265","author":"Dorst","year":"2018","journal-title":"J. Neurol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"498","DOI":"10.1002\/mus.25757","article-title":"ELectron microscopic abnormality and therapeutic efficacy in chronic inflammatory demyelinating polyneuropathy with anti-neurofascin155 immunoglobulin G4 antibody","volume":"57","author":"Kuwahara","year":"2017","journal-title":"Muscle Nerve"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1111\/1744-9987.12532","article-title":"Safety Aspects of Immunoadsorption in IgG Removal Using a Single-Use, Multiple-pass Protein A Immunoadsorber (LIGASORB): Clinical Investigation in Healthy Volunteers","volume":"21","author":"Lehnert","year":"2017","journal-title":"Ther. Apher. Dial."},{"key":"ref_36","first-page":"551","article-title":"Immunoadsorption therapy for Fisher\u2019s syndrome: Analysis of the recovery process of external ophthalmoplegia and the removal ability of anti-GQ1b antibodies","volume":"36","author":"Chida","year":"1996","journal-title":"Rinsho Shinkeigaku"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"419","DOI":"10.1016\/0955-3886(94)90174-0","article-title":"Technical and clinical experience with Protein A Immunoadsorption columns","volume":"15","author":"Belak","year":"1994","journal-title":"Transfus. Sci."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"596","DOI":"10.1136\/jnnp.72.5.596","article-title":"Clinimetric evaluation of a new overall disability scale in immune mediated polyneuropathies","volume":"72","author":"Merkies","year":"2002","journal-title":"J. Neurol. Neurosurg. Psychiatry"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1016\/S1474-4422(17)30470-2","article-title":"Diagnosis of multiple sclerosis: 2017 revisions of the McDonald criteria","volume":"17","author":"Thompson","year":"2017","journal-title":"Lancet Neurol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1914","DOI":"10.1212\/WNL.0b013e3181c47cc2","article-title":"A consensus protocol for the standardization of cerebrospinal fluid collection and biobanking","volume":"73","author":"Teunissen","year":"2009","journal-title":"Neurology"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1111\/j.1529-8027.2010.00245.x","article-title":"European Federation of Neurological Societies\/Peripheral Nerve Society Guideline on management of chronic inflammatory demyelinating polyradiculoneuropathy: Report of a joint task force of the European Federation of Neurological Societies and the Peripheral Nerve Society-First Revision","volume":"15","author":"Pns","year":"2010","journal-title":"J. Peripher. Nerv. Syst."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"e149","DOI":"10.1212\/NXI.0000000000000149","article-title":"Rituximab in treatment-resistant CIDP with antibodies against paranodal proteins","volume":"2","author":"Querol","year":"2015","journal-title":"Neurol. Neuroimmunol. Neuroinflammation"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"559","DOI":"10.1002\/mdc3.12662","article-title":"Remarkable Rituximab Response on Tremor Related to Acute-Onset Chronic Inflammatory Demyelinating Polyradiculoneuropathy in an Antineurofascin155 Immunoglobulin G4-Seropositive Patient","volume":"5","author":"Demichelis","year":"2018","journal-title":"Mov. Disord. Clin. Pr."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"e639","DOI":"10.1212\/NXI.0000000000000639","article-title":"Antibodies to neurofascin, contactin-1, and contactin-associated protein 1 in CIDP: Clinical relevance of IgG isotype","volume":"7","author":"Cortese","year":"2019","journal-title":"Neurol. Neuroimmunol. Neuroinflammation"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1016\/j.jns.2016.03.004","article-title":"Prevalence of neurofascin-155 antibodies in patients with multiple sclerosis","volume":"364","author":"Stich","year":"2016","journal-title":"J. Neurol. Sci."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"201","DOI":"10.3389\/fimmu.2019.00201","article-title":"The Role of B Cells and Antibodies in Multiple Sclerosis, Neuromyelitis Optica, and Related Disorders","volume":"10","author":"Weber","year":"2019","journal-title":"Front. Immunol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"610","DOI":"10.1177\/1352458517706037","article-title":"Multiple sclerosis: Serum anti-CNS autoantibodies","volume":"24","author":"Prineas","year":"2017","journal-title":"Mult. Scler. J."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1046\/j.1468-1331.1999.610071.x","article-title":"Inter-laboratory validation of an ELISA for the determination of serum anti-ganglioside antibodies","volume":"6","author":"Willison","year":"1999","journal-title":"Eur. J. Neurol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"898","DOI":"10.1093\/brain\/awx012","article-title":"Co-cultures with stem cell-derived human sensory neurons reveal regulators of peripheral myelination","volume":"140","author":"Clark","year":"2017","journal-title":"Brain"}],"container-title":["Journal of Clinical Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2077-0383\/9\/7\/2025\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T09:43:44Z","timestamp":1760175824000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2077-0383\/9\/7\/2025"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,6,27]]},"references-count":49,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2020,7]]}},"alternative-id":["jcm9072025"],"URL":"https:\/\/doi.org\/10.3390\/jcm9072025","relation":{},"ISSN":["2077-0383"],"issn-type":[{"value":"2077-0383","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,6,27]]}}}