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Thus, we aimed to discover novel, clinically meaningful CIDP subgroups using unbiased clustering.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>In this observational, multicenter retrospective cohort study we screened 425 patients diagnosed with typical CIDP or CIDP variants from 10 German centers. Standardized data including demographic, clinical, electrophysiological, laboratory, comorbidity, and treatment information were collected. 325 patients were then randomly assigned to the discovery cohort and 100 to the validation cohort. We performed unbiased clustering and post-hoc analysis to identify clusters and define subtypes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Findings<\/jats:title>\n                    <jats:p>\n                      Four distinct clusters showed marked differences:\n                      <jats:list list-type=\"bullet\">\n                        <jats:list-item>\n                          <jats:p>\n                            <jats:italic>Cluster 1<\/jats:italic>\n                            <jats:bold>:<\/jats:bold>\n                            Female patients with high symptom level, high disability scores, ANA positivity and autoimmune comorbidities\n                          <\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>\n                            <jats:italic>Cluster 2<\/jats:italic>\n                            <jats:bold>:<\/jats:bold>\n                            Moderate to low symptom level with low disability scores, demyelination-dominant and less comorbidities\n                          <\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>\n                            <jats:italic>Cluster 3<\/jats:italic>\n                            <jats:bold>:<\/jats:bold>\n                            High symptom level, axonal-demyelinating damage and cardiovascular comorbidities\n                          <\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>\n                            <jats:italic>Cluster 4<\/jats:italic>\n                            <jats:bold>:<\/jats:bold>\n                            Multifocal CIDP with high disability scores as well as frequent ataxia and areflexia\n                          <\/jats:p>\n                        <\/jats:list-item>\n                      <\/jats:list>\n                    <\/jats:p>\n                    <jats:p>Post hoc analyses showed marked differences in disease progression and therapeutic strategies, with clusters 1 and 4 showing particularly high rates of progression and disability.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Interpretation<\/jats:title>\n                    <jats:p>Unbiased clustering revealed four clinically meaningful CIDP subtypes, each exhibiting distinct presentations and trajectories. We identified two red flag subgroups suggesting that CIDP comprises biologically and clinically heterogeneous disease phenotypes. These findings may support more individualized monitoring and therapeutic strategies for high-risk patients and raise the possibility of distinct underlying pathomechanisms across CIDP subgroups.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s00415-026-14221-1","type":"journal-article","created":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T16:16:57Z","timestamp":1792685817000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Clinical heterogeneity in chronic inflammatory demyelinating polyneuropathy: data-driven subtypes challenge current classification"],"prefix":"10.1007","volume":"273","author":[{"given":"Paula","family":"Quint","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Felix","family":"Kohle","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Menekse","family":"Oeztuerk","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeremias","family":"Motte","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna-Lena","family":"Fisse","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frauke","family":"Stascheit","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisa","family":"Gilliam","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alice","family":"De Lorenzo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ali Maisam","family":"Afzali","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katinka","family":"Fischer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul","family":"Disse","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher","family":"Nelke","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Louisa","family":"Mueller-Miny","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne K.","family":"Mausberg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark","family":"Stettner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kalliopi","family":"Pitarokoili","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gerd Meyer","family":"zu Hoerste","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Brunkhorst","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marc","family":"Pawlitzki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefanie","family":"Schreiber","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Achim","family":"Berthele","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bernhard","family":"Hemmer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Schroeter","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sven G.","family":"Meuth","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christina B.","family":"Schroeter","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6332-8650","authenticated-orcid":false,"given":"Tobias","family":"Ruck","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,10,22]]},"reference":[{"issue":"11","key":"14221_CR1","doi-asserted-by":"publisher","first-page":"3556","DOI":"10.1111\/ene.14959","volume":"28","author":"PYK Van Den Bergh","year":"2021","unstructured":"Van Den Bergh PYK, Van Doorn PA, Hadden RDM et al (2021) European Academy of Neurology\/Peripheral Nerve Society guideline on diagnosis and treatment of chronic inflammatory demyelinating polyradiculoneuropathy: report of a joint Task Force\u2014second revision. 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F.K. received research funding from the DFG-funded Cologne Clinician Scientist Program (CCSP), consulting fees from Takeda, honoraria from argenx, and travel support from argenx and Alexion. M.O. has received speaker fees and travel support from Amicus Therapeutics GmbH, ArgenxGermany GmbH, CSL Behring GmbH, Johnson & Johnson; Novartis AG, and Sanofi-Aventis GmbH, travel support from Alnylam\u00ae Pharmaceuticals; and holds stock in Merck KGaA. Her research is supported by the Habilitation Funding Programme of Heinrich-Heine University D\u00fcsseldorf, the German Society for Muscular Diseases (Deutsche Gesellschaft f\u00fcr Muskelkranke e.V., DGM), the Deutsche GBS Stiftung e.V., and the EFRE\/JTF programme(B2B-RARE; EFRE\u221220800340). J.M. reports research funding from Kyverna and Novartis; consulting fees from Kyverna, Johnson & Johnson, Novartis, and Candit; honoraria from argenx, Kyverna, Johnson & Johnson, Novartis, and Candit; and travel support from Kyverna, Johnson & Johnson, Novartis, Candit, and Neuraxpharm. A.-L.F reports consulting fees from Takeda; honoraria from CSL Behring, argenx, and Takeda; travel support from CSL Behring and Takeda; advisory board participation for Takeda; and stock ownership in Novartis and Novo Nordisk. F.S. received consulting fees from Alexion, argenx, Takeda, Octapharma, and Sanofi; honoraria from Alexion, argenx, Takeda, Octapharma, Sanofi, and Novartis; travel support from Alexion and argenx; and participation on advisory boards for Alexion, argenx, Takeda, Sanofi, and Janssen. C.N. received honorary speaker fees from Alexion Pharma, ArgenX, and research support from Alexion Pharma. M.St served on the scientific advisory boards and\/or received speaker honoraria, travel funding or honoraria for medical writing from Annexon; Argenx; Bayer; Biogen; Idec; Biotest; CSLBering; Dianthis; Genzyme. KP has received speaker honoraria from Biogen Idec, Novartis, and Bayer Schering Pharma, CSL Behring, Grifols, ARGENX, Alnylam, Sanofi not related to this work. G.M.z.H. reports scientific project funding from Biogen, speaker honoraria from Amgen and argenx, and advisory board participation for Johnson & Johnson (Janssen) and Immunovant. M. P. reports honoraria from argenx, Alexion, Biogen, Bayer, Demecan, Hexal, Merck, Sanofi, Takeda, Teva, Janssen, Roche, and Novartis, as well as travel support from Alexion, Biogen, Merck, Sanofi, and Novartis. A.B. received research funding from Biogen, Roche, Merck Serono, Alexion, Novartis, and Sanofi; consulting fees from Alexion, Horizon, Roche, Sandoz\/Hexal, Biogen, Neuraxpharm, Hexal, argenx, Johnson & Johnson, and CSL Behring; honoraria from Novartis, Biogen, Alexion, Merck, Roche, and argenx; and travel support from Merck, Alexion, and Roche. S.G.M. reports research funding from public funding agencies, foundations, and industry partners; consulting fees from Medudy; honoraria from Academy 2, argenx, Alexion, Almirall, Amicus Therapeutics Germany, Bayer, Biogen, BioNTech, Bristol Myers Squibb, Celgene, Datamed, Demecan, Diamed, Diaplan, DPMed, Gen Medicine, Genzyme, Hexal, IGES, Impulze, Janssen, KW Medipoint, MedDay, Medudy, Merck Serono, MICE, Mylan, Neuraxpharm, Neuropoint, Novartis, Novo Nordisk, ONO Pharma, Oxford PharmaGenesis, IQVIA (formerly QuintilesIMS), Roche, Sanofi, Springer Medizin Verlag, STADA, Chugai Pharma, Teva, UCB, Viatris, Wings for Life, and Xcenda; and travel support from the same organizations. T.R. reports consulting fees and honoraria from argenx, Alexion, UCB, Johnson & Johnson, Merck, Novartis, Sanofi, and Amgen, as well as advisory board participation for argenx. A.M.A, K.F., P.D., L.M.-M., S.S., B.H., C.B.S., E.G., A.D.L., A.K.M., R.B., M.Sc. have nothing to report.","order":1,"name":"Ethics","label":"Conflicts of interest","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"This study was conducted as a retrospective analysis of routinely collected patient data. All procedures performed were in accordance with the ethical standard of the institutional and national research committee as well as with the 1964 Helsinki Declaration and its later amendments.","order":2,"name":"Ethics","label":"Ethical approval and consent to participate","group":{"name":"EthicsHeading","label":"Declarations"}}],"article-number":"681"}}