Precise identification and tracking of HMGCR-reactive CD4+ T cells in the target tissue of patients with anti-HMGCR immune-mediated necrotising myopathy
Authors' conclusion
HMGCR-antigen-reactive CD4+T-cells are present in the circulation and target tissue of patients with anti-HMGCR+IMNM, suggesting an active role for these cells in the pathogenesis of anti-HMGCR+IMNM.
Study context
- Population
- Patients with anti-HMGCR+ immune-mediated necrotising myopathy (IMNM) and patients with dermatomyositis (DM); peripheral blood mononuclear cells stimulated with HMGCR protein and peptidesNatural antigen processing assay (NAPA) n=6
- Participants
- 10 vs 10
- Comparison
- Patients with anti-HMGCR+ IMNM vs DM
- ANTI-HMGCR+ IMNMn = 10
- DMn = 10reference
- Outcome
- HMGCR-reactive CD4+ T-cell responses (CD154 upregulation by flow cytometry) and their presence in affected muscle tissue
Methodological detailscase-control comparison, flow cytometry, TCR β sequencing
- Case-control comparison
- Flow cytometry
- TCR β sequencing
Main finding
As reported in the abstract
CD4+ T-cell responses to HMGCR protein
ANTI-HMGCR+ IMNM
0.06
median
DM
0.00
median
P = 0.0059
- When present, responses positively correlated with anti-HMGCR antibody levels
- r2=0.89, p=0.0012
Further findings
| Outcome | ANTI-HMGCR+ IMNM | DM | Projection score | P value |
|---|---|---|---|---|
| Response to at least one HMGCR peptide | 9/10 events | 1/10 events | P = 0.0003 | |
| HMGCR-reactive TCR β antigen-reactive motifs enriched in muscle biopsies (projection score) | 0.03 vs 0.63 | P = 0.007 |
NAPA peptide presentation
- Convergent presentation of seven HMGCR core peptides, with substantial overlap in peptide repertoires between patients
Original publication
Precise identification and tracking of HMGCR-reactive CD4+ T cells in the target tissue of patients with anti-HMGCR immune-mediated necrotising myopathy. Ann Rheum Dis. Published 2 January 2025. doi:10.
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