Novel Biomarkers May Distinguish Persistent from Self-Limiting Disease Course in Arthritis

dna genetics
The study profiles the gene expression signatures of rheumatoid arthritis and other inflammatory joint disorders compared with healthy controls.

Study data published in Scientific Reports profile the gene expression signatures of rheumatoid arthritis (RA) and other inflammatory joint disorders compared with healthy controls. Candidate biomarkers of these signatures were able to distinguish persistent from self-limiting disease course in patients with early, drug-naïve arthritis.   

This gene expression profiling study enrolled adult patients who presented with peripheral joint symptoms to a clinic in the United Kingdom. Eligible patients had no prior exposure to disease-modifying anti-rheumatic drugs (DMARDs) or corticosteroids.

Patients provided venous blood samples and were assessed by a consultant rheumatologist at baseline, 6 months, and 12 months. Patients were classified by arthritic symptoms into 4 diagnostic categories: RA, undifferentiated arthritis, self-limiting arthritis, or non-inflammatory arthralgia. 

RA and undifferentiated arthritis represented “persistent” inflammatory disease compared with self-limiting arthritis and non-inflammatory arthralgia. Venous blood samples were also taken from 23 healthy laboratory workers, who comprised the control group. Peripheral blood mononuclear cells were isolated from patient and control blood samples. Diagnostic outcomes were compared between patients who initiated DMARDs during the study course and patients who did not.

A common type I interferon gene signature was observed in all persistent inflammatory arthritis groups. In patients with RA, the interferon signature was characterized by preferential expression of SIGLEC1 (P =.00597) and MS4A4A (P =.00000904). Just 1 gene (ST6GALNAC1) distinguished undifferentiated arthritis from RA and self-limiting arthritis (P =.0023). At baseline, 6 months and 12 months, markers MSA4A (area under the curve [AUC] values: 0.894, 0.644, 0.720, respectively), PDZK1IP1 (0.785, 0.806, 0.977), and EPHB2 (0.794, 0.723, 0.620) showed fair to excellent discrimination between RA and healthy controls. However, the signature scores of these same genes showed no discriminatory ability between self-limiting arthritis, non-inflammatory arthralgia, and undifferentiated arthritis compared to controls. Only PDZK1IP1 emerged as a fair predictor of self-limiting arthralgia over controls (AUC: 0.701).

A modest effect of conventional synthetic DMARD treatment was observed on gene expression. A significant trend in reduced expression of MS4A4A and IFIT1 was observed at 6 months post-treatment initiation in the RA group. In patients with undifferentiated arthritis, a non-significant trend for reduced expression was observed for IFI27, SIGLEC1, IFI44L and PDZK1IP1 at 12 months.

These data present subset-specific expression patterns of candidate biomarker genes in patients with inflammatory arthritis. These candidate biomarkers were able to distinguish RA from self-limiting disease and non-inflammatory disease. Certain genes were also associated with treatment response.

As study limitations, investigators cited the small sample size and the heterogeneous expression of disease across each diagnostic category. Replication in a larger cohort is necessary to further elucidate the gene signature of early RA.

“[T]his study has potentially identified a type I IFN gene signature in the periphery of drug naïve patients with persistent arthritis and SLA as a promising biomarker,” investigators wrote.

Disclosure: Several study authors declared affiliations with the pharmaceutical industry. Please see the original reference for a full list of authors’ disclosures.


Seyhan AA, Gregory B, Cribbs AP, et al. Novel biomarkers of a peripheral blood interferon signature associated with drug-naïve early arthritis patients distinguish persistent from self-limiting disease course. Sci Rep. 2020;10(1):8830.