HLA variation analysis and autoantigen epitope prediction in idiopathic inflammatory myopathies
Main finding · HLA-C*07:01 in IIM (protective)Result — go to the resultOdds ratio 0.17 95% CI 0.06–0.41Authors' conclusion
In the anti-Mi2 subgroup, we identified novel HLA alleles, amino acid variants and immunogenic epitopes, supporting a role for HLA-restricted antigen presentation in disease pathogenesis and indicating candidate targets for antigen-specific immunotherapy. However, the HLA/epitope findings related to anti-Mi2 are exploratory due to limited power, and require confirmation in larger cohorts together with experimental validation.
Study context
- Population
- Biopsy-confirmed idiopathic inflammatory myopathy (IIM) patients and ethnically matched healthy controls
- Participants
- 147 vs 114
- Comparison
- Biopsy-confirmed IIM vs ethnically matched healthy controls
- IIMn = 147
- Healthy controlsn = 114reference
- Outcome
- HLA allele and amino acid associations with clinical and autoantibody-defined IIM subgroups, and predicted immunogenic epitopes presented by subgroup-specific HLA alleles
Methodological detailsobservational, ethnically matched controls, high-resolution HLA genotyping, in silico epitope prediction
- Observational
- Ethnically matched controls
- High-resolution HLA genotyping
- In silico epitope prediction
Main finding
HLA-C*07:01 in IIM (protective)
Odds ratio
0.17
95% CI 0.06–0.41
Pa = 1.23 × 10-2
IIMvs Healthy controls
OR 0.17 (95% CI 0.06–0.41); Pa = 1.23 × 10-2
As reported in the abstract
Observational data: associations, not effects.
Further findings
| Outcome | OR (95% CI) | P value | |
|---|---|---|---|
| HLA-A*33:03 in DMDMvs Healthy controls | 14.8 (4.38–68.07) | Pa = 3.97 × 10-3 | |
| DQB1*06:03 in PMPMvs Healthy controls | 7.24 (2.42–22.61) | Pa = 2.40 × 10-2 | |
| HLA alleles in anti-Mi2 subgroupAnti-Mi2vs Healthy controlsA*33:03 · exploratory due to limited power | 19.73 (5.11–98.01) | Pa = 2.82 × 10-3 | |
| HLA alleles in anti-Mi2 subgroupAnti-Mi2vs Healthy controlsDQA1*02:01 · exploratory due to limited power | 10.28 (2.33–53.75) | Pa = 1.03 × 10-2 | |
| HLA alleles in anti-Mi2 subgroupAnti-Mi2vs Healthy controlsDQB1*03:03 · exploratory due to limited power | 8.99 (2.71–30.51) | Pa = 1.98 × 10-2 | |
| B*08:01 in anti-Ro52Anti-Ro52vs Healthy controls | 11.67 (3.56–39.83) | Pa = 2.94 × 10-3 | |
| 0.050.21520Odds ratio (log scale) |
Fine mapping of amino acid variant
- Phenylalanine at position 25 of DQA1 pinpointed to the risk allele DQA1*02:01 in anti-Mi2a/b autoantibody positive patients
Predicted Mi-2 epitopes
- From 49 predicted Mi-2 peptides, 'YYKYILTR', 'QAFSRAHR' and 'DYWEKLLR' bound stably to A*33:03 and were non-allergenic and non-toxic
Original publication
HLA variation analysis and autoantigen epitope prediction in idiopathic inflammatory myopathies. Rheumatology (Oxford). Published 27 February 2026. doi:10.
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