Evidence map›Paper›PMID 28258082›Full record

ArticleNeurology2017

DPPX antibody-associated encephalitis: Main syndrome and antibody effects.

Makoto Hara, Helena Ariño, Mar Petit-Pedrol, Lidia Sabater, Maarten J Titulaer, Eugenia Martinez-Hernandez, Marco W J Schreurs, Myrna R Rosenfeld, Francesc Graus, Josep Dalmau

Open access · greenAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Neurology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 86 papers, 5 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
86citing papers in PubMed, 5 pooled it
10.9field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

86 citing papers in PubMed, 5 syntheses or guidelines pooled it, 216 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
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  4. Rapidly progressive dementia and intractable diarrhea: a teaching case report and a systematic review of cognitive impairment in Whipple's disease.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2022
    Pooled it
  5. Pooled it
  6. Autoimmune Encephalitis in Acute Care-Pathology, Diagnosis, and Management.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026
    Review
  7. Article
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  9. Article
  10. Review
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  13. Autoimmune neuropsychiatric disorders manifesting with psychosis.The Journal of clinical investigation · 2025
    Review
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  15. Article
  16. Article
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  18. Article
  19. Voltage Gated Ion Channels and Sleep.The Journal of membrane biology · 2024
    Review
  20. Review

26 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors at 2 institutions in 2 countries.

Makoto HaraFrom the Clinical and Experimental Neuroimmunology Program (M.H., H.A., M.P.-P., L.S., E.M.-H., M.R.R., F.G., J.D.), August Pi Sunyer Biomedical Research Institute, Hospital Clínic, University of Barcelona, Spain; Division of Neurology (M.H.), Department of Medicine, Nihon University School of Medicine, Tokyo, Japan; Biomedical Research Networking Centre for Rare Diseases (H.A., J.D., M.P.-P., L.S., E.M.-H., M.R.R.), Valencia, Spain; Departments of Neurology (M.J.T.) and Immunology (M.W.J.S.), Erasmus Medical Center, Rotterdam, the Netherlands; Department of Neurology (M.R.R., J.D.), University of Pennsylvania, Philadelphia; and Catalan Institution for Research and Advanced Studies (J.D.), Barcelona, Spain.
Helena AriñoFrom the Clinical and Experimental Neuroimmunology Program (M.H., H.A., M.P.-P., L.S., E.M.-H., M.R.R., F.G., J.D.), August Pi Sunyer Biomedical Research Institute, Hospital Clínic, University of Barcelona, Spain; Division of Neurology (M.H.), Department of Medicine, Nihon University School of Medicine, Tokyo, Japan; Biomedical Research Networking Centre for Rare Diseases (H.A., J.D., M.P.-P., L.S., E.M.-H., M.R.R.), Valencia, Spain; Departments of Neurology (M.J.T.) and Immunology (M.W.J.S.), Erasmus Medical Center, Rotterdam, the Netherlands; Department of Neurology (M.R.R., J.D.), University of Pennsylvania, Philadelphia; and Catalan Institution for Research and Advanced Studies (J.D.), Barcelona, Spain.
Mar Petit-PedrolFrom the Clinical and Experimental Neuroimmunology Program (M.H., H.A., M.P.-P., L.S., E.M.-H., M.R.R., F.G., J.D.), August Pi Sunyer Biomedical Research Institute, Hospital Clínic, University of Barcelona, Spain; Division of Neurology (M.H.), Department of Medicine, Nihon University School of Medicine, Tokyo, Japan; Biomedical Research Networking Centre for Rare Diseases (H.A., J.D., M.P.-P., L.S., E.M.-H., M.R.R.), Valencia, Spain; Departments of Neurology (M.J.T.) and Immunology (M.W.J.S.), Erasmus Medical Center, Rotterdam, the Netherlands; Department of Neurology (M.R.R., J.D.), University of Pennsylvania, Philadelphia; and Catalan Institution for Research and Advanced Studies (J.D.), Barcelona, Spain.
Lidia SabaterFrom the Clinical and Experimental Neuroimmunology Program (M.H., H.A., M.P.-P., L.S., E.M.-H., M.R.R., F.G., J.D.), August Pi Sunyer Biomedical Research Institute, Hospital Clínic, University of Barcelona, Spain; Division of Neurology (M.H.), Department of Medicine, Nihon University School of Medicine, Tokyo, Japan; Biomedical Research Networking Centre for Rare Diseases (H.A., J.D., M.P.-P., L.S., E.M.-H., M.R.R.), Valencia, Spain; Departments of Neurology (M.J.T.) and Immunology (M.W.J.S.), Erasmus Medical Center, Rotterdam, the Netherlands; Department of Neurology (M.R.R., J.D.), University of Pennsylvania, Philadelphia; and Catalan Institution for Research and Advanced Studies (J.D.), Barcelona, Spain.
Maarten J TitulaerFrom the Clinical and Experimental Neuroimmunology Program (M.H., H.A., M.P.-P., L.S., E.M.-H., M.R.R., F.G., J.D.), August Pi Sunyer Biomedical Research Institute, Hospital Clínic, University of Barcelona, Spain; Division of Neurology (M.H.), Department of Medicine, Nihon University School of Medicine, Tokyo, Japan; Biomedical Research Networking Centre for Rare Diseases (H.A., J.D., M.P.-P., L.S., E.M.-H., M.R.R.), Valencia, Spain; Departments of Neurology (M.J.T.) and Immunology (M.W.J.S.), Erasmus Medical Center, Rotterdam, the Netherlands; Department of Neurology (M.R.R., J.D.), University of Pennsylvania, Philadelphia; and Catalan Institution for Research and Advanced Studies (J.D.), Barcelona, Spain.
Eugenia Martinez-HernandezFrom the Clinical and Experimental Neuroimmunology Program (M.H., H.A., M.P.-P., L.S., E.M.-H., M.R.R., F.G., J.D.), August Pi Sunyer Biomedical Research Institute, Hospital Clínic, University of Barcelona, Spain; Division of Neurology (M.H.), Department of Medicine, Nihon University School of Medicine, Tokyo, Japan; Biomedical Research Networking Centre for Rare Diseases (H.A., J.D., M.P.-P., L.S., E.M.-H., M.R.R.), Valencia, Spain; Departments of Neurology (M.J.T.) and Immunology (M.W.J.S.), Erasmus Medical Center, Rotterdam, the Netherlands; Department of Neurology (M.R.R., J.D.), University of Pennsylvania, Philadelphia; and Catalan Institution for Research and Advanced Studies (J.D.), Barcelona, Spain.
Marco W J SchreursFrom the Clinical and Experimental Neuroimmunology Program (M.H., H.A., M.P.-P., L.S., E.M.-H., M.R.R., F.G., J.D.), August Pi Sunyer Biomedical Research Institute, Hospital Clínic, University of Barcelona, Spain; Division of Neurology (M.H.), Department of Medicine, Nihon University School of Medicine, Tokyo, Japan; Biomedical Research Networking Centre for Rare Diseases (H.A., J.D., M.P.-P., L.S., E.M.-H., M.R.R.), Valencia, Spain; Departments of Neurology (M.J.T.) and Immunology (M.W.J.S.), Erasmus Medical Center, Rotterdam, the Netherlands; Department of Neurology (M.R.R., J.D.), University of Pennsylvania, Philadelphia; and Catalan Institution for Research and Advanced Studies (J.D.), Barcelona, Spain.
Myrna R RosenfeldFrom the Clinical and Experimental Neuroimmunology Program (M.H., H.A., M.P.-P., L.S., E.M.-H., M.R.R., F.G., J.D.), August Pi Sunyer Biomedical Research Institute, Hospital Clínic, University of Barcelona, Spain; Division of Neurology (M.H.), Department of Medicine, Nihon University School of Medicine, Tokyo, Japan; Biomedical Research Networking Centre for Rare Diseases (H.A., J.D., M.P.-P., L.S., E.M.-H., M.R.R.), Valencia, Spain; Departments of Neurology (M.J.T.) and Immunology (M.W.J.S.), Erasmus Medical Center, Rotterdam, the Netherlands; Department of Neurology (M.R.R., J.D.), University of Pennsylvania, Philadelphia; and Catalan Institution for Research and Advanced Studies (J.D.), Barcelona, Spain.
Francesc GrausFrom the Clinical and Experimental Neuroimmunology Program (M.H., H.A., M.P.-P., L.S., E.M.-H., M.R.R., F.G., J.D.), August Pi Sunyer Biomedical Research Institute, Hospital Clínic, University of Barcelona, Spain; Division of Neurology (M.H.), Department of Medicine, Nihon University School of Medicine, Tokyo, Japan; Biomedical Research Networking Centre for Rare Diseases (H.A., J.D., M.P.-P., L.S., E.M.-H., M.R.R.), Valencia, Spain; Departments of Neurology (M.J.T.) and Immunology (M.W.J.S.), Erasmus Medical Center, Rotterdam, the Netherlands; Department of Neurology (M.R.R., J.D.), University of Pennsylvania, Philadelphia; and Catalan Institution for Research and Advanced Studies (J.D.), Barcelona, Spain.
Josep DalmauFrom the Clinical and Experimental Neuroimmunology Program (M.H., H.A., M.P.-P., L.S., E.M.-H., M.R.R., F.G., J.D.), August Pi Sunyer Biomedical Research Institute, Hospital Clínic, University of Barcelona, Spain; Division of Neurology (M.H.), Department of Medicine, Nihon University School of Medicine, Tokyo, Japan; Biomedical Research Networking Centre for Rare Diseases (H.A., J.D., M.P.-P., L.S., E.M.-H., M.R.R.), Valencia, Spain; Departments of Neurology (M.J.T.) and Immunology (M.W.J.S.), Erasmus Medical Center, Rotterdam, the Netherlands; Department of Neurology (M.R.R., J.D.), University of Pennsylvania, Philadelphia; and Catalan Institution for Research and Advanced Studies (J.D.), Barcelona, Spain. Jdalmau@clinic.cat.
University of Pennsylvania · USNihon University · JP

Funding

Paraneoplastic Disorders of the CNS: Autoantigen ProfilingR01NS077851 · NINDS · UNIVERSITY OF PENNSYLVANIA · PI DALMAU, JOSEP O. · 2011 to 2015
$1.9M
NINDS NIH HHS R01 NS077851
6 · The paper itself

Abstract

objectiveTo report the main syndrome of dipeptidyl-peptidase-like protein 6 (DPPX) antibody-associated encephalitis, immunoglobulin G (IgG) subclass, and the antibody effects on DPPX/Kv4.2 potassium channels.

methodsA retrospective analysis of new patients and cases reported since 2013 was performed. IgG subclass and effects of antibodies on cultured neurons were determined with described techniques.

resultsNine new patients were identified (median age 57 years, range 36-69 years). All developed severe prodromal weight loss or diarrhea followed by cognitive dysfunction (9), memory deficits (5), CNS hyperexcitability (8; hyperekplexia, myoclonus, tremor, or seizures), or brainstem or cerebellar dysfunction (7). The peak of the disease was reached 8 months (range 1-54 months) after onset. All patients had both IgG4 and IgG1 DPPX antibodies. In cultured neurons, the antibodies caused a decrease of DPPX clusters and Kv4.2 protein that was reversible on removal of the antibodies. Considering the current series and previously reported cases (total 39), 67% developed the triad: weight loss (median 20 kg; range 8-53 kg)/gastrointestinal symptoms, cognitive-mental dysfunction, and CNS hyperexcitability. Outcome was available from 35 patients (8 not treated with immunotherapy): 60% had substantial or moderate improvement, 23% had no improvement (most of them not treated), and 17% died. Relapses occurred in 8 of 35 patients (23%) and were responsive to immunotherapy.

conclusionsDPPX antibodies are predominantly IgG1 and IgG4 and associate with cognitive-mental deficits and symptoms of CNS hyperexcitability that are usually preceded by diarrhea, other gastrointestinal symptoms, and weight loss. The disorder is responsive to immunotherapy, and this is supported by the reversibility of the antibody effects in cultured neurons.

Indexed as

EncephalitisAdultAgedAnimalsCells, CulturedDipeptidyl-Peptidases and Tripeptidyl-PeptidasesDose-Response Relationship, DrugElectroencephalographyEmbryo, MammalianFemaleFollow-Up StudiesHippocampusHumansImmunoglobulin GImmunotherapyMagnetic Resonance ImagingDipeptidyl-Peptidases and Tripeptidyl-PeptidasesDPP6 protein, humanImmunoglobulin GNerve Tissue ProteinsPotassium ChannelsProtein AggregatesShal Potassium Channels

Identifiers

PMID28258082
PMCPMC5379928
OpenAlexW2593303678

What OpenQuestion holds

Textmetadata
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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.