Background/Purpose: Systemic Lupus Erythematosus (SLE) is a complex autoimmune disease, partly driven by Interferon-alpha (IFN-α). Studies suggest that anti-IFN-α antibodies (AIAA) may neutralize IFN-α, potentially reducing disease activity, promoting clinical quiescence despite serologic activity, and increasing the risk of infections.

Methods: SLE patients meeting the revised 1997 ACR/EULAR criteria who attended rheumatology services at a tertiary care center in India between July 2024 and February 2025, along with healthy controls, were enrolled. Exclusion criteria included active infections, juvenile SLE, pregnancy, and lactation. Data collected included baseline demographics, disease characteristics and activity, steroid dose at the time of sampling, and history of infections.Disease activity was assessed using SLEDAI (with HDA defined as ≥10 and LDA as ≤4) and numerical BILAG scores, with BILAG scores prioritized in case of conflict. LDA patients were further classified as either serologically active (SACQ) or serologically and clinically quiescent (SQCQ).Serum IFN-α and AIAA levels were measured using ELISA (GENLISA kits, Krishgen Biosystems); detection ranges were 7.82–500 pg/mL for IFN-α and 16–256 pg/mL for AIAA. Levels were compared between patients and controls and correlated with disease duration, clinical features, anti-dsDNA, complement levels, ESR, steroid dose, and disease activity.ROC curve analysis was performed to evaluate and compare the sensitivity and specificity of various markers in predicting disease activity. A p-value < 0.05 was considered statistically significant. Written informed consent was obtained from all participants.

Results: A total of 117 lupus patients (112 females) and 30 healthy controls (24 females) were included. Baseline characteristics are shown in Table 1. IFN-α levels were significantly higher in patients [median(IQR): 15.989(8.18-22.370)]compared to healthy controls (median: 0). They were undetectable in 29 cases and all controls with a p-value < 0.0001. Surprisingly, AIAA levels were significantly higher in healthy controls [median(IQR): 146.74(21.29-45.4)) than in patients [median(IQR): 31.34(32.06-303.31)], p-value < 0.0001.IFN-α positively correlated with ESR, c-SLEDAI, and BILAG scores. AIAA showed no correlation with any parameter. No significant differences in IFN-α or AIAA levels were seen between disease activity groups (LDA, HDA, SACQ, SQCQ) or clinical features or prior infections. Steroid dose showed no correlation with either IFN-α or AIAA (Table 2).Upon comparison of IFN-α and AIAA with traditional markers such as ESR, dsDNA, C3, and C4, the conventional markers demonstrated superior performance in predicting disease activity.

Conclusion: IFN-α levels correlated with higher disease activity, as measured by BILAG scores. Established markers anti-dsDNA, C3, C4, and ESR performed better than interferon as a biomarker of disease activity.AIAA levels were not predictive of disease status or clinical phenotype. AIAA presence was not associated with infections or disease flares. If reproducible , the higher AIAA levels in healthy controls may suggest a protective role against autoimmunity.

Table 1- Baseline Demographics and Clinical Manifestations

Table 2-Baseline Disease Activity status, Biomarkers and Infection history

Table 3- Correlation coefficients (r) between IFN-α, AIAA and various clinical/laboratory variables. * indicates statistical significance.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/interferon-%ce%b1-anti-interferon-alpha-antibodies-and-disease-activity-in-systemic-lupus-erythematosus/