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Case Reports
. 2025 Nov;12(11):2367-2371.
doi: 10.1002/acn3.70179. Epub 2025 Aug 26.

Single-Cell RNA Seq in Sydenham Chorea Shows B Cell HLA-DR/DQ Upregulation and Plasma Cell Proteasomal Activation

Velda X Han  1   2   3 , Brooke A Keating  1 , Brian S Gloss  4 , Xianzhong Lau  5 , Ruwani Dissanayake  6 , Hiroya Nishida  1 , Jessica Hayes  1 , Shrujna Patel  1   7   8 , Shekeeb S Mohammad  1   7 , Russell C Dale  1   7   8
Affiliations
Case Reports

Single-Cell RNA Seq in Sydenham Chorea Shows B Cell HLA-DR/DQ Upregulation and Plasma Cell Proteasomal Activation

Velda X Han et al. Ann Clin Transl Neurol. 2025 Nov.

Abstract

The pathogenesis of Sydenham chorea remains unclear. We report a 10-year-old girl presenting with subacute chorea and mild carditis following Streptococcal throat infection. Single-cell RNA sequencing on 30,794 peripheral immune cells from the patient and two sex-matched controls revealed nine immune cell clusters. We found up-regulated antigen processing pathways in B cells, monocytes, and eosinophils, enriched by HLA genes, particularly HLA-DRB5 and HLA-DQB1, and immunoglobulin (IGH) genes in B cells. Up-regulated proteasomal pathways in plasma cells were enriched by PSM genes. These insights support the B cell-mediated autoantibody hypothesis in Sydenham chorea. We highlight the potential of scRNA-seq in rare diseases to inform targeted therapies.

Keywords: autoimmune brain disorder; neuroimmunology; neuropsychiatric; transcriptomics.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

FIGURE 1
FIGURE 1
(A) Dot plot of top 5 up‐ and down‐regulated GSEA GO pathways across cell types in SC patient vs. control. Significant pathways (FDR < 0.05) were simplified [9], and only those that were present in > 2 cell types were plotted. In SC patient vs. control, antigen processing, MHC protein complex pathways were up‐regulated in classical monocytes, eosinophils, and B cells, and down‐regulated in plasma B cells. Other innate immune pathways (‘defence response to other organisms’) were up‐regulated in neutrophils, but down‐regulated in CD8 T cells and plasma B cells. (B) Connectivity network plot of the up‐regulated ‘antigen binding’ pathway in classical monocytes, eosinophils, and B cells was plotted. The antigen binding pathways were enriched by HLA genes (HLA‐DR and HLA‐DQ genes) across cell types and immunoglobulin heavy and light chain (IGH, IGL genes) in B cells.
FIGURE 2
FIGURE 2
(A) Bar chart of top 5 up‐ and down‐regulated Gene Set Enrichment Analysis (GSEA) Gene Ontology (GO) pathways in plasma B cells. (B) Connectivity network plot of the up‐regulated ‘proteasomal complex’ pathway in plasma B cells was plotted, enriched by PSM genes, which are proteasomal structural and regulatory genes.
See this image and copyright information in PMC

References

    1. Zühlke L. J. and Steer A. C., “Estimates of the Global Burden of Rheumatic Heart Disease,” Global Heart 8, no. 3 (2013): 189–195. - PubMed
    1. Eyre M., Thomas T., Ferrarin E., et al., “Treatments and Outcomes Among Patients With Sydenham Chorea: A Meta‐Analysis,” JAMA Network Open 7, no. 4 (2024): e246792. - PMC - PubMed
    1. Poomarimuthu M., Ramasamy T., Govindan R., et al., “Association of HLA‐DRB1 Alleles With Rheumatic Fever and Rheumatic Heart Disease: A Meta‐Analysis,” Immunological Investigations 51, no. 2 (2022): 221–232. - PubMed
    1. Gray L.‐A., D'Antoine H. A., Tong S. Y. C., et al., “Genome‐Wide Analysis of Genetic Risk Factors for Rheumatic Heart Disease in Aboriginal Australians Provides Support for Pathogenic Molecular Mimicry,” Journal of Infectious Diseases 216, no. 11 (2017): 1460–1470. - PubMed
    1. Church A. J., Cardoso F., Dale R. C., et al., “Anti‐Basal Ganglia Antibodies in Acute and Persistent Sydenham's Chorea,” Neurology 59, no. 2 (2002): 227–231. - PubMed

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