Summary
A six-patient preprint found higher interferon-related gene scores in blood samples associated with dermatomyositis flares. The feasibility study used weekly at-home blood microsampling and RNA sequencing.
A small feasibility study found that interferon-related gene activity was higher in blood samples collected around disease flares in people with dermatomyositis. The preprint involved six women followed for six months and suggests that repeated blood-based gene measurements could be investigated as a way to monitor this autoimmune disease over time.
The findings are preliminary: three of the six participants experienced a flare, and the authors describe interferon signatures as candidate biomarkers requiring further study rather than as a clinical monitoring test.
How the study tracked disease activity
Dermatomyositis is an inflammatory autoimmune disease that can affect the muscles and skin. Interferons are immune-signalling proteins, and an interferon gene signature is a pattern of gene activity associated with interferon-related immune responses.
The researchers enrolled patients whose disease was inactive or minimally active and who met at least one additional condition: diagnosis within the previous two years, a documented flare during the preceding year, or ongoing reduction of immunosuppressive treatment. All six participants were female, with ages ranging from 46 to 72 years at study entry. Their myositis-specific antibody profiles included two patients with anti-MDA5 antibodies, two with anti-Mi2 antibodies, one with anti-NXP2 antibodies and one without detected myositis-specific antibodies.
Participants assessed their disease activity at home every week for six months using the International Myositis Assessment and Clinical Study group patient global assessment, a numerical rating scale from 0 to 10. A flare was defined as an increase of more than 2 points that continued for two consecutive weeks. Such changes triggered an in-person physician visit for confirmation.
At the same time, participants collected weekly blood microsamples at home. Each sample contained 125 microlitres of blood and was sent by courier to the study centre. The researchers performed RNA sequencing on 54 samples collected across nine timepoints using an Illumina platform. The analysis examined changes in gene expression and RNA processing during flares.
Interferon activity was higher around flares
Three participants experienced a flare during follow-up. The mean RNA integrity score for the weekly microsamples was 7.61, with a standard deviation of 0.64, indicating that the samples provided usable RNA for the study's sequencing analysis.
Interferon scores were significantly higher in samples associated with flares than in samples not associated with flares. A linear mixed-effects model that treated individual patients as random intercepts produced a P value of 5.13 × 10⁻⁴. This model accounts for the fact that multiple samples came from the same participants.
A separate gene-set enrichment analysis also found enrichment of interferon-related gene sets in samples collected before and during flares. The interferon-alpha-response and interferon-gamma-response gene sets had the highest positive normalized enrichment scores among the hallmark gene sets examined.
Why the approach matters
Dermatomyositis flares can be difficult to identify early, and the study was designed to examine whether frequent, minimally invasive sampling could capture biological changes close to a flare. Home collection allowed samples to be gathered repeatedly between in-person assessments, while RNA sequencing provided a way to examine coordinated changes in immune-related gene activity rather than a single laboratory measurement.
The results support further investigation of interferon-related signatures as candidate biomarkers for longitudinal disease monitoring. However, this was a preprint feasibility study with six participants and three observed flares. Its main contribution is showing that the home-sampling and transcriptomic workflow could be carried out and that flare-associated interferon patterns were detectable in this small group. Larger studies will be needed to assess how consistently the signal appears across patients and whether it can support reliable early monitoring in clinical practice.