Evidence map›Paper›PMID 29788256›Full record

ArticleBrain : a journal of neurology2018

Distinct HLA associations of LGI1 and CASPR2-antibody diseases.

Sophie Binks, James Varley, Wanseon Lee, Mateusz Makuch, Katherine Elliott, Jeffrey M Gelfand, Saiju Jacob, M Isabel Leite, Paul Maddison, Mian Chen and 9 more

Open access · hybridAbstract read
In one paragraph

Article in Brain : a journal of neurology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 84 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
84citing papers in PubMed, 2 pooled it
11.0field-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

84 citing papers in PubMed, 2 syntheses or guidelines pooled it, 156 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Trial
  4. Review
  5. Article
  6. Article
  7. Article
  8. [Role of HLA genetic variants in autoimmune diseases].Zhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciences · 2026
    Review
  9. Article
  10. Review
  11. Review
  12. Article
  13. Article
  14. Observational
  15. Article
  16. Article
  17. Autoimmune encephalitis.Nature reviews. Disease primers · 2025
    Review
  18. Article
  19. Article
  20. Autoimmune encephalitis-associated epilepsy.Nature reviews. Neurology · 2025
    Review

24 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

19 authors at 6 institutions in 3 countries.

Sophie BinksOxford Autoimmune Neurology Group, Nuffield Department of Clinical Neurosciences, University of Oxford, Level 3, West Wing, John Radcliffe Hospital, Oxford, OX3 9DS, UK.
James VarleyOxford Autoimmune Neurology Group, Nuffield Department of Clinical Neurosciences, University of Oxford, Level 3, West Wing, John Radcliffe Hospital, Oxford, OX3 9DS, UK.
Wanseon LeeWellcome Centre for Human Genetics, University of Oxford, Oxford, OX3 7BN, UK.
Mateusz MakuchOxford Autoimmune Neurology Group, Nuffield Department of Clinical Neurosciences, University of Oxford, Level 3, West Wing, John Radcliffe Hospital, Oxford, OX3 9DS, UK.
Katherine ElliottWellcome Centre for Human Genetics, University of Oxford, Oxford, OX3 7BN, UK.
Jeffrey M GelfandUCSF Department of Neurology, 675 Nelson Rising Lane, San Francisco, CA 94158, USA.
Saiju JacobCentre for Rare Diseases and Queen Elizabeth Neuroscience Centre, University Hospitals Birmingham, UK.
M Isabel LeiteOxford Autoimmune Neurology Group, Nuffield Department of Clinical Neurosciences, University of Oxford, Level 3, West Wing, John Radcliffe Hospital, Oxford, OX3 9DS, UK.
Paul MaddisonDepartment of Neurology, Queen's Medical Centre, Derby Road, Nottingham NG7 2UH, UK.
Mian ChenTransplant Immunology and Immunogenetics Laboratory, Oxford Transplant Centre, Churchill Hospital, Oxford, UK.
Michael D GeschwindUCSF Department of Neurology, 675 Nelson Rising Lane, San Francisco, CA 94158, USA.
Eleanor GrantOxford Autoimmune Neurology Group, Nuffield Department of Clinical Neurosciences, University of Oxford, Level 3, West Wing, John Radcliffe Hospital, Oxford, OX3 9DS, UK.
Arjune SenOxford Autoimmune Neurology Group, Nuffield Department of Clinical Neurosciences, University of Oxford, Level 3, West Wing, John Radcliffe Hospital, Oxford, OX3 9DS, UK.
Patrick WatersOxford Autoimmune Neurology Group, Nuffield Department of Clinical Neurosciences, University of Oxford, Level 3, West Wing, John Radcliffe Hospital, Oxford, OX3 9DS, UK.
Mark McCormackDepartment of Molecular and Cellular Therapeutics, the Royal College of Surgeons in Ireland, Dublin, Ireland.
Gianpiero L CavalleriDepartment of Molecular and Cellular Therapeutics, the Royal College of Surgeons in Ireland, Dublin, Ireland.
Martin BarnardoTransplant Immunology and Immunogenetics Laboratory, Oxford Transplant Centre, Churchill Hospital, Oxford, UK.
Julian C KnightWellcome Centre for Human Genetics, University of Oxford, Oxford, OX3 7BN, UK.
Sarosh R IraniOxford Autoimmune Neurology Group, Nuffield Department of Clinical Neurosciences, University of Oxford, Level 3, West Wing, John Radcliffe Hospital, Oxford, OX3 9DS, UK.
John Radcliffe Hospital · GBCentre for Human Genetics · GBChurchill Hospital · GBRoyal College of Surgeons in Ireland · IEUniversity of California, San Francisco · USQueen's Medical Centre · GB

Funding

Predicting progression of human prion diseaseR01AG031189 · NIA · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI GESCHWIND, MICHAEL D · 2008 to 2017
$5.7M
Arthritis Research UK 20773NIA NIH HHS L30 AG024892NIA NIH HHS R01 AG031189Wellcome TrustWellcome Trust 090532/Z/09/ZWellcome Trust 104079/Z/14/ZWellcome Trust 204969/Z/16/Z
6 · The paper itself

Abstract

The recent biochemical distinction between antibodies against leucine-rich, glioma-inactivated-1 (LGI1), contactin-associated protein-2 (CASPR2) and intracellular epitopes of voltage-gated potassium-channels (VGKCs) demands aetiological explanations. Given established associations between human leucocyte antigen (HLA) alleles and adverse drug reactions, and our clinical observation of frequent adverse drugs reactions in patients with LGI1 antibodies, we compared HLA alleles between healthy controls (n = 5553) and 111 Caucasian patients with VGKC-complex autoantibodies. In patients with LGI1 antibodies (n = 68), HLA-DRB1*07:01 was strongly represented [odds ratio = 27.6 (95% confidence interval 12.9-72.2), P = 4.1 × 10-26]. In contrast, patients with CASPR2 antibodies (n = 31) showed over-representation of HLA-DRB1*11:01 [odds ratio = 9.4 (95% confidence interval 4.6-19.3), P = 5.7 × 10-6]. Other allelic associations for patients with LGI1 antibodies reflected linkage, and significant haplotypic associations included HLA-DRB1*07:01-DQA1*02:01-DQB1*02:02, by comparison to DRB1*11:01-DQA1*05:01-DQB1*03:01 in CASPR2-antibody patients. Conditional analysis in LGI1-antibody patients resolved further independent class I and II associations. By comparison, patients with both LGI1 and CASPR2 antibodies (n = 3) carried yet another complement of HLA variants, and patients with intracellular VGKC antibodies (n = 9) lacked significant HLA associations. Within LGI1- or CASPR2-antibody patients, HLA associations did not correlate with clinical features. In silico predictions identified unique CASPR2- and LGI1-derived peptides potentially presented by the respective over-represented HLA molecules. These highly significant HLA associations dichotomize the underlying immunology in patients with LGI1 or CASPR2 antibodies, and inform T cell specificities and cellular interactions at disease initiation.10.1093/brain/awy109_video1awy109media15796480660001.

Indexed as

AdultAgedAged, 80 and overAllelesAutoantibodiesEpitopesFemaleGene FrequencyGenetic LinkageHaplotypesHLA AntigensHLA-DRB1 ChainsHumansIntracellular Signaling Peptides and ProteinsMaleMembrane ProteinsAutoantibodiesCNTNAP2 protein, humanEpitopesHLA AntigensHLA-DRB1 ChainsIntracellular Signaling Peptides and ProteinsLGI1 protein, humanMembrane ProteinsNerve Tissue ProteinsPotassium Channels, Voltage-GatedProteins

Identifiers

PMID29788256
PMCPMC6118231
OpenAlexW2804644440

What OpenQuestion holds

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Registered trials

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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.