Evidence map›Paper›PMID 38888758›Full record

ArticleActa neuropathologica2024

Inter-alpha-trypsin inhibitor heavy chain H3 is a potential biomarker for disease activity in myasthenia gravis.

Christina B Schroeter, Christopher Nelke, Frauke Stascheit, Niklas Huntemann, Corinna Preusse, Vera Dobelmann, Lukas Theissen, Marc Pawlitzki, Saskia Räuber, Alice Willison and 16 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Acta neuropathologica, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.

0numbers the graph read from it
0cells of the map it votes in
12citing papers in PubMed
–field-weighted citation impact
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

12 citing papers in PubMed.

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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

26 authors.

Christina B Schroeter *Department of Neurology, Medical Faculty and University Hospital Düsseldorf, Heinrich Heine University, Moorenstr. 5, 40225, Düsseldorf, Germany.ORCID 0000-0002-1391-7817
Christopher Nelke *Department of Neurology, Medical Faculty and University Hospital Düsseldorf, Heinrich Heine University, Moorenstr. 5, 40225, Düsseldorf, Germany.
Frauke StascheitDepartment of Neurology, Charité - Universitätsmedizin Berlin, 10117, Berlin, Germany.
Niklas HuntemannDepartment of Neurology, Medical Faculty and University Hospital Düsseldorf, Heinrich Heine University, Moorenstr. 5, 40225, Düsseldorf, Germany.
Corinna PreusseDepartment of Neuropathology, Charité - Universitätsmedizin Berlin, Bonhoefferweg 3, 10117, Berlin, Germany.
Vera DobelmannDepartment of Neurology, Medical Faculty and University Hospital Düsseldorf, Heinrich Heine University, Moorenstr. 5, 40225, Düsseldorf, Germany.
Lukas TheissenDepartment of Neurology, Medical Faculty and University Hospital Düsseldorf, Heinrich Heine University, Moorenstr. 5, 40225, Düsseldorf, Germany.
Marc PawlitzkiDepartment of Neurology, Medical Faculty and University Hospital Düsseldorf, Heinrich Heine University, Moorenstr. 5, 40225, Düsseldorf, Germany.
Saskia RäuberDepartment of Neurology, Medical Faculty and University Hospital Düsseldorf, Heinrich Heine University, Moorenstr. 5, 40225, Düsseldorf, Germany.
Alice WillisonDepartment of Neurology, Medical Faculty and University Hospital Düsseldorf, Heinrich Heine University, Moorenstr. 5, 40225, Düsseldorf, Germany.
Anna VogelsangDepartment of Neurology, Medical Faculty and University Hospital Düsseldorf, Heinrich Heine University, Moorenstr. 5, 40225, Düsseldorf, Germany.
Adela Della MarinaDepartment of Neuropaediatrics, Neuromuscular Centre, Universitätsmedizin Essen, Hufelandstr. 55, 45122, Essen, Germany.
Hans-Peter HartungDepartment of Neurology, Medical Faculty and University Hospital Düsseldorf, Heinrich Heine University, Moorenstr. 5, 40225, Düsseldorf, Germany.
Nico MelzerDepartment of Neurology, Medical Faculty and University Hospital Düsseldorf, Heinrich Heine University, Moorenstr. 5, 40225, Düsseldorf, Germany.
Felix F KonenDepartment of Neurology, Hannover Medical School, 30625, Hannover, Germany.
Thomas SkripuletzDepartment of Neurology, Hannover Medical School, 30625, Hannover, Germany.
Andreas HentschelLeibniz-Institut Für Analytische Wissenschaften - ISAS - E.V, 44227, Dortmund, Germany.
Simone KönigCore Unit Proteomics, Interdisciplinary Center for Clinical Research, Medical Faculty, University of Münster, 48149, Münster, Germany.
Michaela SchweizerElectron Microscopy Unit, Center for Molecular Neurobiology Hamburg, University Medical Center Hamburg-Eppendorf, 20251, Hamburg, Germany.
Kai StühlerInstitute for Molecular Medicine, Proteome Research, University Hospital and Medical Faculty, Heinrich Heine University, 40225, Duesseldorf, Germany.
Gereon PoschmannInstitute for Molecular Medicine, Proteome Research, University Hospital and Medical Faculty, Heinrich Heine University, 40225, Duesseldorf, Germany.
Andreas RoosDepartment of Neurology, Medical Faculty and University Hospital Düsseldorf, Heinrich Heine University, Moorenstr. 5, 40225, Düsseldorf, Germany.
Werner StenzelDepartment of Neuropathology, Charité - Universitätsmedizin Berlin, Bonhoefferweg 3, 10117, Berlin, Germany.
Andreas Meisel *Department of Neurology, Charité - Universitätsmedizin Berlin, 10117, Berlin, Germany.
Sven G Meuth *Department of Neurology, Medical Faculty and University Hospital Düsseldorf, Heinrich Heine University, Moorenstr. 5, 40225, Düsseldorf, Germany.
Tobias Ruck *Department of Neurology, Medical Faculty and University Hospital Düsseldorf, Heinrich Heine University, Moorenstr. 5, 40225, Düsseldorf, Germany. Tobias.ruck@med.uni-duesseldorf.de.

Funding

Ministry of Culture and Science of North Rhine-Westphalia PROFILNRW-2020-107-A
6 · The paper itself

Abstract

Myasthenia gravis is a chronic antibody-mediated autoimmune disease disrupting neuromuscular synaptic transmission. Informative biomarkers remain an unmet need to stratify patients with active disease requiring intensified monitoring and therapy; their identification is the primary objective of this study. We applied mass spectrometry-based proteomic serum profiling for biomarker discovery. We studied an exploration and a prospective validation cohort consisting of 114 and 140 anti-acetylcholine receptor antibody (AChR-Ab)-positive myasthenia gravis patients, respectively. For downstream analysis, we applied a machine learning approach. Protein expression levels were confirmed by ELISA and compared to other myasthenic cohorts, in addition to myositis and neuropathy patients. Anti-AChR-Ab levels were determined by a radio receptor assay. Immunohistochemistry and immunofluorescence of intercostal muscle biopsies were employed for validation in addition to interactome studies of inter-alpha-trypsin inhibitor heavy chain H3 (ITIH3). Machine learning identified ITIH3 as potential serum biomarker reflective of disease activity. Serum levels correlated with disease activity scores in the exploration and validation cohort and were confirmed by ELISA. Lack of correlation between anti-AChR-Ab levels and clinical scores underlined the need for biomarkers. In a subgroup analysis, ITIH3 was indicative of treatment responses. Immunostaining of muscle specimens from these patients demonstrated ITIH3 localization at the neuromuscular endplates in myasthenia gravis but not in controls, thus providing a structural equivalent for our serological findings. Immunoprecipitation of ITIH3 and subsequent proteomics lead to identification of its interaction partners playing crucial roles in neuromuscular transmission. This study provides data on ITIH3 as a potential pathophysiological-relevant biomarker of disease activity in myasthenia gravis. Future studies are required to facilitate translation into clinical practice.

Indexed as

BiomarkersMyasthenia GravisProteinase Inhibitory Proteins, SecretoryAdultAgedAutoantibodiesCohort StudiesFemaleHumansMachine LearningMaleMiddle AgedProteomicsReceptors, CholinergicYoung AdultAutoantibodiesBiomarkersProteinase Inhibitory Proteins, SecretoryReceptors, CholinergicAcetylcholine receptorBiomarkerInter-alpha-trypsin inhibitor heavy chain H3Muscle proteomicsMyasthenia gravisNeuromuscular junction

Identifiers

PMID38888758
PMCPMC11195637

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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.