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Prospective study of cancer survival in patients with HuD-antibody-associated paraneoplastic neurological disorders
  1. Paul Maddison1,
  2. Bethan Lang2,
  3. Selina Thomsen2,
  4. Teresa C Moloney2,
  5. Paul Gozzard3,
  6. Caroline J Chapman4,
  7. Victoria Barnard5,
  8. Berne Ferry5,
  9. Angela Vincent6,7
  1. 1 Department of Neurology, Nottingham University Hospitals NHS Trust, Nottingham, Nottingham, UK
  2. 2 Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, Oxfordshire, UK
  3. 3 Department of Neurology, Sheffield Teaching Hospitals NHS Foundation Trust, Royal Hallamshire Hospital, Sheffield, UK
  4. 4 Department of Pathology, Nottingham University Hospitals NHS Trust, Queen’s Medical Centre, Nottingham, UK
  5. 5 Clinical Laboratory Immunology, Churchill Hospital, Oxford, Oxfordshire, UK
  6. 6 Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, UK
  7. 7 Department of Neurosciences, Weatherall Institute of Molecular Medicine, Oxford, Oxfordshire, UK
  1. Correspondence to Dr Paul Maddison, Department of Neurology, Nottingham University Hospitals NHS Trust, Nottingham, Nottingham, UK; paul.maddison{at}

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The appearance of a paraneoplastic neurological disorder (PND) with Hu-antibodies, often before tumour detection, together with spontaneous tumour regression in a few patients, suggests that immune responses to HuD, possibly mediated by cytotoxic T-cells, could be beneficial to the patient.1 Nevertheless, in previous retrospective studies, survival in Hu-antibody-associated PNDs (Hu-Ab/PNDs) in general was similar to those in patients with small-cell lung cancer (SCLC) without neurological illness.2 3

Here we studied, for the first time prospectively, tumour outcomes in a large series of patients with Hu-Ab/PNDs, comparing with contemporaneous patients with SCLC without neurological symptoms.



Written consent was obtained from all patients. From July 2012 to June 2015 prospectively we collected all serum samples that were positive for Hu-antibodies at Oxford University Hospitals as part of routine diagnostic testing via referral from any of England’s 152 acute hospital trusts. Diagnostic categorisation of associated PNDs was agreed between the research team and the referring physician, in line with published diagnostic criteria.4 For survival comparisons, contemporaneous control data and pre-treatment serum samples were obtained prospectively from 245 patients with SCLC, without PNDs, from the Nottingham Trent region over the same time period. Serum samples were stored at −80°C and retested for Hu and SOX2 antibodies by ELISA, and paraneoplastic antibodies tested on frozen rat cerebellum with positive results confirmed using a multi-line blot (Ravo Diagnostika, Freiburg, Germany) (see online supplemental methods).

Supplemental material


Statistical analysis

Survival statistics from date of SCLC diagnosis in PND and control groups were calculated using log-rank tests, and differences in cancer survival according to presence of PNDs and Hu-antibodies were evaluated using a Cox proportional hazards model.


Patients with Hu-antibody PNDs and SCLC controls

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  • Contributors PM contributed to study conception, data collection, design, analysis, writing of the first draft and revising the manuscript for important intellectual content. BL, ST, TM, PG, CJC, VB, BF and AV contributed to data collection, analysis, review of the first draft and revising the manuscript for important intellectual content.

  • Funding PG was supported by a fellowship grant from Myaware (UK).

  • Competing interests Bethan Lang and Angela Vincent are co-applicants and receive royalties on patent application WO/2010/046716 entitled ‘Neurological Autoimmune Disorders’. The patent has been licensed to Euroimmun AG for the development of assays for LGI1 and other VGKC-complex antibodies. All other authors have no conflicts of interests.

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

  • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.