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*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

162 Citations (Scopus)

Abstract

Objective: To 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. Methods: A 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. Results: Nine 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. Conclusions: DPPX antibodies are predominantly IgG1 and IgG4 and associate with cognitivemental 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.

Original languageEnglish
Pages (from-to)1340-1348
Number of pages9
JournalNeurology
Volume88
Issue number14
DOIs
Publication statusPublished - 4 Apr 2017

Bibliographical note

Funding Information:
Research Support, Government Entities: (1) supported by the Netherlands Organisation for Scientific Research (NWO, Veni incentive and Memorabel initiative).

Publisher Copyright:
© 2017 The Author(s). Published by Wolters Kluwer Health, Inc.

Research programs

  • EMC MM-02-72-02

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