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Neuromuscular
Original research
Clinical relevance of distinguishing autoimmune nodopathies from CIDP: longitudinal assessment in a large cohort
  1. Merel C Broers1,
  2. Luuk Wieske2,
  3. Ece Erdag1,3,
  4. Cemre Gürlek1,4,
  5. Carina Bunschoten1,
  6. Pieter A van Doorn1,
  7. Filip Eftimov2,
  8. Krista Kuitwaard1,5,
  9. Juna M de Vries1,
  10. Marie-Claire Y de Wit6,
  11. Mariska MP Nagtzaam1,
  12. Suzanne C Franken1,
  13. Louisa Zhu1,4,
  14. Manuela Paunovic1,
  15. Maurice de Wit1,
  16. Marco WJ Schreurs4,
  17. Cinta Lleixà7,
  18. Lorena Martín-Aguilar7,
  19. Elba Pascual-Goñi7,
  20. Luis Querol7,8,
  21. Bart C Jacobs1,4,
  22. Ruth Huizinga4,
  23. Maarten J Titulaer1
  1. 1 Department of Neurology, Erasmus MC, University Medical Center, Rotterdam, The Netherlands
  2. 2 Department of Neurology, Amsterdam Neuroscience, Amsterdam UMC, location AMC, Amsterdam, The Netherlands
  3. 3 Department of Neuroscience, Aziz Sancar Institute of Experimental Medicine, Istanbul University, Istanbul, Turkey
  4. 4 Department of Immunology, Erasmus MC, University Medical Center, Rotterdam, The Netherlands
  5. 5 Department of Neurology, Albert Schweitzer Hospital, Dordrecht, The Netherlands
  6. 6 Department of Pediatric Neurology, Erasmus MC, Erasmus MC Sophia Children's Hospital, Rotterdam, The Netherlands
  7. 7 Neuromuscular Diseases Unit, Department of Neurology, Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain
  8. 8 Centro para la de Investigación Biomédica en Red en Enfermedades Raras, CIBERER, Madrid, Spain
  1. Correspondence to Dr Maarten J Titulaer, Neurology, Erasmus MC, Rotterdam, Zuid-Holland, The Netherlands; m.titulaer{at}erasmusmc.nl

Abstract

Background The aim of this study was to determine treatment response and whether it is associated with antibody titre change in patients with autoimmune nodopathy (AN) previously diagnosed as chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), and to compare clinical features and treatment response between AN and CIDP.

Methods Serum IgG antibodies to neurofascin-155 (NF155), contactin-1 (CNTN1) and contactin-associated protein 1 (CASPR1) were detected with cell-based assays in patients diagnosed with CIDP. Clinical improvement was determined using the modified Rankin scale, need for alternative and/or additional treatments and assessment of the treating neurologist.

Results We studied 401 patients diagnosed with CIDP and identified 21 patients with AN (10 anti-NF155, 6 anti-CNTN1, 4 anti-CASPR1 and 1 anti-NF155/anti-CASPR1 double positive). In patients with AN ataxia (68% vs 28%, p=0.001), cranial nerve involvement (34% vs 11%, p=0.012) and autonomic symptoms (47% vs 22%, p=0.025) were more frequently reported; patients with AN improved less often after intravenous immunoglobulin treatment (39% vs 80%, p=0.002) and required additional/alternative treatments more frequently (84% vs 34%, p<0.001), compared with patients with CIDP. Antibody titres decreased or became negative in patients improving on treatment. Treatment withdrawal was associated with a titre increase and clinical deterioration in four patients.

Conclusions Distinguishing CIDP from AN is important, as patients with AN need a different treatment approach. Improvement and relapses were associated with changes in antibody titres, supporting the pathogenicity of these antibodies.

  • clinical neurology
  • neuroimmunology
  • peripheral neuropathology

Data availability statement

Data are available upon reasonable request. Data supporting the findings of this study are available upon reasonable request, in accordance with privacy regulations.

https://doi.org/10.1136/jnnp-2023-331378

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    Data availability statement

    Data are available upon reasonable request. Data supporting the findings of this study are available upon reasonable request, in accordance with privacy regulations.

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    Footnotes

    • RH and MJT contributed equally.

    • Contributors MB: Designed and conceptualised study; major role in the acquisition of data; analysed the data; interpreted the data; drafted the manuscript for intellectual content. LW: Major role in the acquisition of data; interpreted the data; revised the manuscript for intellectual content. EE: Major role in the acquisition of data; analysed the data; interpreted the data; revised the manuscript for intellectual content. CG: Major role in the acquisition of data; analysed the data; interpreted the data; revised the manuscript for intellectual content. CB: Role in the acquisition of data; interpreted the data; revised the manuscript for intellectual content. PAvD: Role in the acquisition of data; interpreted the data; revised the manuscript for intellectual content. FE: Role in the acquisition of data; interpreted the data; revised the manuscript for intellectual content. KK: Role in the acquisition of data; analysed the data; interpreted the data; revised the manuscript for intellectual content. JMdV: Role in the acquisition of data; interpreted the data; revised the manuscript for intellectual content. M-CYdW: Role in the acquisition of data. MN: Major role in the acquisition of data; analysed the data; interpreted the data; revised the manuscript for intellectual content. SF: Role in the acquisition of data; analysed the data; interpreted the data; revised the manuscript for intellectual content. LZ: Role in the acquisition of data; analysed the data; interpreted the data; revised the manuscript for intellectual content. MP: Role in the acquisition of data; analysed the data; interpreted the data; revised the manuscript for intellectual content. MdW: Role in the acquisition of data; analysed the data; interpreted the data; revised the manuscript for intellectual content. MS: Role in the acquisition of data; analysed the data; interpreted the data; revised the manuscript for intellectual content. CL: Role in the acquisition of data; analysed the data; interpreted the data. LM-A: Role in the acquisition of data; analysed the data; interpreted the data. EPG: Role in the acquisition of data; analysed the data; interpreted the data. LQ: Role in the acquisition of data; analysed the data; interpreted the data; revised the manuscript for intellectual content. BCJ: Role in the acquisition of data; interpreted the data; revised the manuscript for intellectual content. RH: Designed and conceptualised study; role in the acquisition of data; analysed the data; interpreted the data; revised the manuscript for intellectual content. MT: Designed and conceptualised study; role in the acquisition of data; analysed the data; interpreted the data; revised the manuscript for intellectual content. RH and MT are responsible for the overall content as the guarantors.

    • Funding This study was funded by Dutch Prinses Beatrix Spierfonds (W.OR16-18).

    • Competing interests MB reports grants from the Dutch Prinses Beatrix Spierfonds (W.OR16-18). LW reports grants from Grifols and the GBS/CIDP Foundation for the study of disease activity biomarkers in CIDP. EE is supported by the Scientific and Technological Research Council of Turkey (TUBITAK) BIDEB-2219 Postdoctoral Research Program. MT was supported by the Erasmus MC Pain Foundation, has received funding from ZonMw (Memorabel programme), the Dutch EpilepsieNL Foundation (NEF 19-08), Dioraphte (2001 0403) and E-RARE JTC 2018 (UltraAIE, 90030376505). PAvD reports grants from Prinses Beatrix Spierfonds, The Netherlands Organisation for Health Research and Development (ZonMW), Sanquin Blood supply, Takeda and Grifols, he is a member of Scientific Advisory Committee/Steering Committee Trials for Annexon, Argenx, Hansa, Octapharma, Sanofi and Roche, all grants and fees were paid to his institution. FE reports grants from ZonMw (Dutch Governmental Agency) and Prinses Beatrix Spierfonds (Dutch Charity Organization) and grants from CSLBehring, Kedrion, Terumo BCT, Grifols and Takeda Pharmaceutical Company, outside the submitted work. Grants were paid to institution and are used for investigator-initiated randomised controlled trials and studies within INCbase, an international CIDP registry. In addition, he received consultancy fee from UCB Pharma, Sanofi and Grifols, paid to institution, outside the submitted work. KK reports grants from Takeda and Grifols (SPIN award). LQ reports grant from Instituto de Salud Carlos III – Ministry of Economy and Innovation (Spain), Fundació La Marató, GBS-CIDP Foundation International, Novartis Pharma Spain, Roche, UCB and Grifols, and received speaker or expert testimony honoraria from CSL Behring, Novartis, Sanofi-Genzyme, Merck, Annexon, Biogen, Janssen, ArgenX, UCB, LFB, Octapharma and Roche, and serves at Clinical Trial Steering Committee for Sanofi Genzyme and Roche, and is Principal Investigator for UCB’s CIDP01 trial. BCJ reports grants for research from Baxalta, Grifols, CSL-Behring, Annexon, Hansa Biopharma, Roche, Prinses Beatrix Spierfonds, GBS-CIDP Foundation International and Horizon 2020, and consultancy fees from Roche and Annexon, and he is chair of the Steering Committee of Internation GBS Outcome Study (IGOS) and member of the Steering Committee of International CIDP Outcome Study (ICOS) and INCbase. RH reports grants from Health~Holland, GBS-CIDP Foundation and Grifols. The ICOS was supported by funding from CSL-Behring and Grifols.

    • Provenance and peer review Not commissioned; externally peer reviewed.

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