Evidence map›Paper›PMID 35624318›Full record

ArticleJournal of neurology2022

Rho GTPase-activating protein 10 (ARHGAP10/GRAF2) is a novel autoantibody target in patients with autoimmune encephalitis.

Sven Jarius, Lars Komorowski, Jens U Regula, Jürgen Haas, Stefanie Brakopp, Brigitte Wildemann

Open access · hybridAbstract read
In one paragraph

Article in Journal of neurology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
0.7field-weighted citation impact, top 28% 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

6 citing papers in PubMed, 6 citations in OpenAlex.

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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

6 authors at 2 institutions in 1 country.

Sven JariusMolecular Neuroimmunology Group, Department of Neurology, University of Heidelberg, Heidelberg, Germany. sven.jarius@med.uni-heidelberg.de.
Lars KomorowskiInstitute for Experimental Immunology, EUROIMMUN Medizinische Labordiagnostika AG, Lübeck, Germany.
Jens U RegulaDepartment of Neurology, University of Heidelberg, Heidelberg, Germany.
Jürgen HaasMolecular Neuroimmunology Group, Department of Neurology, University of Heidelberg, Heidelberg, Germany.
Stefanie BrakoppInstitute for Experimental Immunology, EUROIMMUN Medizinische Labordiagnostika AG, Lübeck, Germany.
Brigitte WildemannMolecular Neuroimmunology Group, Department of Neurology, University of Heidelberg, Heidelberg, Germany.
Heidelberg University · DEEuroimmun Medizinische Labordiagnostika (Germany) · DE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundIn 2010, we described a novel immunoglobulin G (IgG) autoantibody (termed anti-Ca after the index case) targeting Rho GTPase-activating protein 26 (ARHGAP26, also termed GTPase regulator associated with focal adhesion kinase [GRAF], or oligophrenin-like protein 1 [OPHN1L]) in autoimmune cerebellar ataxia (ACA). Later, ARHGAP26-IgG/anti-Ca was reported in patients with limbic encephalitis/cognitive decline or peripheral neuropathy. In several of the reported cases, the syndrome was associated with cancer. ARHGAP10/GRAF2, which is expressed throughout the central nervous system, shares significant sequence homology with ARHGAP26/GRAF. Mutations in the ARHGAP10 gene have been linked to cognitive and psychiatric symptoms and schizophrenia.

objectiveTo assess whether ARHGAP26-IgG/anti-Ca co-reacts with ARHGAP10.

methodsSerological testing for ARHGAP10/GRAF2 autoantibodies by recombinant cell-based assays and isotype and IgG subclass analyses.

results26/31 serum samples (84%) from 9/12 (75%) ARHGAP26-IgG/anti-Ca-positive patients and 4/6 ARHGAP26-IgG/anti-Ca-positive CSF samples from four patients were positive also for ARHGAP10-IgG. ARHGAP10-IgG (termed anti-Ca2) remained detectable in the long-term (up to 109 months) and belonged mainly to the complement-activating IgG1 subclass. Median ARHGAP26-IgG/anti-Ca and median ARHGAP10-IgG/anti-Ca2 serum titres were 1:3200 and 1:1000, respectively, with extraordinarily high titres in some samples (ARHGAP26-IgG/anti-Ca: up to 1:1000,000; ARHGAP10-IgG: up to 1:32,000). ARHGAP26/anti-Ca serum titres exceeded those of ARHGAP10-IgG in all samples but one. A subset of patients was positive also for ARHGAP10-IgM and ARHGAP10-IgA. CSF/serum ratios and antibody index calculation suggested intrathecal production of ARHGAP26-IgG/anti-Ca and anti-ARHGAP10. Of 101 control samples, 100 were completely negative for ARHGAP10-IgG; a single control sample bound weakly (1:10) to the ARHGAP10-transfected cells.

conclusionsWe demonstrate that a substantial proportion of patients with ARHGAP26-IgG/anti-Ca-positive autoimmune encephalitis co-react with ARHGAP10. Further studies on the clinical and diagnostic implications of ARHGAP10-IgG/anti-Ca2 seropositivity in patients with autoimmune encephalitis are warranted.

Indexed as

Cerebellar AtaxiaEncephalitisAutoantibodiesGTPase-Activating ProteinsHashimoto DiseaseHumansImmunoglobulin GAutoantibodiesGTPase-Activating ProteinsImmunoglobulin Grho GTPase-activating proteinAntibodiesAnti-CaAnti-Ca2AntigenAutoantibodiesAutoimmune encephalitisCerebellar ataxiaCognitive declineGRAF2GTPase regulator associated with focal adhesion kinase (GRAF)Immunoglobulin G (IgG)Limbic encephalitisMedusa head ataxiaOligophrenin-like protein 1 (OPHN1L)PolyneuropathyRho GTPase-activating protein 10 (ARHGAP10)Rho GTPase-activating protein 26 (ARHGAP26)

Identifiers

PMID35624318
PMCPMC9468106
OpenAlexW4281939002

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.