Cellular immune endophenotypes separating early and late-onset myasthenia gravis
https://doi.org/10.48723/9gg8-ry45
This dataset is made up of single-cell omics files from 16 individuals with myasthenia gravis at various stages of the disease and with differing disease onset age. The samples have been acquired 8+8 on a 10X Genomics Chromium 3.0 system (https://www.10xgenomics.com/platforms/chromium) on two consecutive days and all sequenced in a NovaSeq instrument (https://www.illumina.com/systems/sequencing-platforms/novaseq.html) in the same run. For each of the two experimental days, the data has been hash-tagged and then mixed. Complicating the matter somewhat, there are three sets of files (= three 10X serial IDs) for each day, each of whom contains cells that are a hashed mixture of all eight individuals from this day. Furthermore, four different kinds of data is available for each cell: RNA sequences (GE), B-cell receptor sequences (ENRB), T-cell receptor sequences (ENRT) and RNA-tagged surface-protein binding antibodies (HTO). The last portion contains a set of 10 lineage marker antibodies as well as the hashing antibodies. Further, considering that each set of files is made up of four lanes, and each lane has one file per direction, the total number of files is 6x4x4x2=192 files.
This is the abstract from the forthcoming publication:
The two main subgroups of autoimmune myasthenia gravis, a neuromuscular junction disorder associated with muscle weakness, are the early and late-onset forms, defined by onset before or after 50 years of age. Both carry acetylcholine-receptor autoantibodies, but differ in sex ratios, genetics and occurrence of disease-specific thymus inflammation. By applying multimodal techniques, including deep spectral cytometric phenotyping and single cell sequencing to peripheral blood and thymocyte samples we explored the possibility to discriminate the two forms by cellular immune phenotyping. Analyzing two independent cohorts we identified distinct immunological differences driven by three main lymphocyte populations. Lower frequencies of mucosa-associated invariant T cells and naïve CD8 T cells were observed in late-onset myasthenia, suggesting enhanced immune senescence. Further, a highly differentiated, canonical natural killer cell population was reduced in early-onset myasthenia, which was negatively correlated with degree of thymic inflammation. Using only the frequency of these three populations, correct myasthenia subgroup assignment could be predicted with an accuracy of 90%. These findings identify diverging cellular immune phenotypes between early and late-onset disease, indicating distinct underlying immunopathogenic processes. Together with demographic and disease subgroup-specific features, this may improve clinical classification, in turn of relevance for channeling to interventions.
The dataset consists of 192 files in fastq format, compressed with gzip, and 42 files in other formats (pdf, csv, docx, and txt). Please, see documentations files, Readme.txt and file_list.csv, for details. The total size of the dataset is approximately 450 GiB.
Documentation files
Documentation files
Citation and access
Citation and access
Data access level:
Creator/Principal investigator(s):
Research principal:
Data contains personal data:
Yes
Type of personal data:
Single-cell RNA sequencing data that theoretically can be associated to an individual through the individually unique combination of normal genetic variants. The data is also pseudonymised.
Code key exists:
Yes
Sensitive personal data:
Yes
Citation:
Language:
Method and outcome
Method and outcome
Unit of analysis:
Population:
Patients with myasthenia gravis without ongoing immunomodulating treatments but of whom 5/16 have undergone a thymectomy.
Time method:
Study design:
- Observational study
- Experimental study
- Diagnostic study
Sampling procedure:
Description of sampling:
Samples were selected through availability from an existing biobank of myasthenia gravis patient samples.
Time period(s) investigated:
Samples/material - Existing from scientific collection/biobank
Samples/material - Existing from scientific collection/biobank
Name:
Stockholm Council Biobank
Type(s) of sample:
Peripheral blood mononuclear cells
Geographic coverage
Geographic coverage
Geographic location:
Geographic description:
The samples have all been collected at the Karolinska University Hospital Neurology department.
Administrative information
Administrative information
Responsible department/unit:
Department of Clinical Neuroscience [K8]
Other research principals:
Commissioning organisation:
- Karolinska Institutet
Opens a new window at ror.org.
ROR
Identifiers
Identifiers
Github page:
Ethical Review
Ethical Review
Reviewer:
- Swedish Ethical Review Authority
components.catalogue.resource.content.administrativeInformation.ethicalReview.rorId.srText
ROR
Registration number:
2024-02236-02
Funding
Funding
Funding agency:
- Swedish Research Council
Opens a new window at ror.org.
ROR
Award number:
2023-00533_VR
Award title:
Characterization and optimization of myasthenia gravis care
Funding information:
Myasthenia gravis (MG; OrphaCode 391490; ICD-10 G70.0) is a chronic autoimmune disease affecting neuromuscular signal transmission, with an estimated prevalence of 15 to 25 per 100.000. Disease severity varies from milder forms with potential for long-term remission to severe life-threatening disease. Clinical management is still mainly based on empirical evidence, with a scarcity of reliable clinical predictors or biomarkers for disease sub-form stratification and long-term outcomes. As a consequence, treatment practices vary both within and between countries. We will here perform a nationwide registry linkage study in Sweden to establish more precise prevalence/incidence rates and candidate clinical predictors of long-term outcomes, also including patient-reported outcomes and epidemiological questionnaire data. These findings will be corroborated, extended and cross-compared in large and well-characterized cohorts from 5 countries across Europe reflecting different geographic areas, patient populations and treatment practices. Finally, using advanced immunological methods we will identify novel immunological markers for MG sub-form characterization and disease severity prediction to be validated in a multicenter prospective, observational study of new onset MG. The knowledge thus gained has the potential to change treatment practices with currently available interventions and to be informative for future intervention studies.
Topic and keywords
Topic and keywords
Swedish Standard Classification of Research Subjects 2025:
Keywords:
Relations
Relations
Publications
Publications
Citation:
Theorell J, Ruffin N, Fower A, Sorini C, Ambrose P, Damato V, Handunnetthi L, Leite I, Irani SR, Brauner S, Handel AE, Piehl F. Cellular immune endophenotypes separating early and late-onset myasthenia gravis. JCI Insight. 2025 Nov 27:e199679. doi: 10.1172/jci.insight.199679.
