The results of a new longitudinal analysis cast doubt on the utility of serial interferon assessment.
Baseline evaluation of interferon (IFN)-stimulated genes (ISGs) may be a useful tool for assessing patients with systemic lupus erythematosus (SLE), but the assessment does not appear to be valuable as a long-term biomarker to track changes in disease activity, according to a new report published in Lupus Science & Medicine.
Investigators from Monash University, in Australia, explained that the role of type 1 IFNs in SLE pathogenesis has become clear thanks to genome-wide expression analyses and the fact that most patients with SLE have upregulated ISGs.
However, although a point-in-time analysis suggests that between 60% and 80% of patients with SLE have upregulated ISGs, it is not known whether and how changes in IFN status in individual patients might align with symptoms or affect outcomes.
In an effort to answer that question, the study authors collected blood samples and clinical data from 205 patients at a single tertiary lupus center. A total of 729 samples were analyzed. Patients were followed for a median of 644 days. The results were published in the journal Lupus Science & Medicine.
The patients were classified based on their IFN levels as either IFN high or IFN low. At baseline, the majority of patients (62.9%) were considered IFN high, and 30.2% were considered IFN low. The remaining 6.8% were considered borderline.
Of the initial 205 patients, 142 patients had at least 2 samples taken. Analysis of postbaseline samples showed that in the large majority of cases (87.3%), patients had stable ISG status over time, meaning patients initially in the high category remained in the high category, and those in the low category remained in the low category.
However, IFN status did appear to correlate with certain disease characteristics.
“In longitudinal follow-up, IFN high patients had higher activity in multiple organ domains and spent less time in Lupus Low Disease Activity State, but IFN score did not correlate with SLE Disease Activity Index in individual patients,” the authors wrote.
Among the roughly 1 in 8 patients who did see a fluctuation of ISG across time, most were taking high-dose glucocorticoids (GCs). Patients taking lower doses did not exhibit ISG suppression, they added.
“We confirmed findings from a smaller previous studies that IFN status was strongly associated with differences in disease severity when IFN high and low groups overall were compared,” the authors concluded. “Despite this, IFN status was remarkably stable in the majority of patients with SLE, with almost all of the small proportion of patients whose ISG changed being those treated with high-dose GCs, and ISG results did not correlate with disease activity in individual patients.”
However, 4 patients in the study had a single higher reading, followed by stable lower results, which could not be explained by high-dose immunosuppression.
“The cause of one-off high ISG results in otherwise IFN low patients with SLE is unknown, however it could be hypothesized that a single high reading related to a transient viral infection,” they said.
The investigators noted that there were some limitations to their study. For instance, some of the subsets were small in size, and most of the patients had a long duration of disease. The authors said it may be helpful to examine patients earlier in the disease course for comparison.
Overall, though, the authors said the data suggest stable ISG assessments, meaning their usefulness beyond a one-time baseline score may be limited.
“This suggests that IFN status has prognostic significance in the management of SLE,” they wrote. “However, IFN status is remarkably stable across time and did not correlate with disease activity in individual patients, suggesting that a single baseline evaluation, rather than serial testing, is likely to be informative.”
Northcott M, Jones S, Koelmeyer R, et al. Type 1 interferon status in systemic lupus erythematosus: a longitudinal analysis. Lupus Sci Med. 2022;9(1):e000625. doi:10.1136/lupus-2021-000625