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Updated: May 5, 2026
High-throughput Quantitative Real-time RT-PCR Assay for Determining Expression Profiles of Types I and III Interferon Subtypes
Published on: March 24, 2015
Type I interferon gene expression signature as a marker to predict response to cyclophosphamide based treatment in
Sree Nethra Bulusu1, Christina Mary Mariaselvam1, Sanket Shah1
1Department of Clinical Immunology, Jawaharlal Institute of Postgraduate Medical Education and Research (JIPMER), Puducherry, India.
Insights
Cyclophosphamide treatment impacts the type-I interferon signature in lupus nephritis. A significant decrease in the interferon-gene based score predicts treatment non-response, especially when combined with specific histopathological features.
Area of Science:
- Immunology
- Nephrology
- Genetics
Background:
- Systemic lupus erythematosus (SLE) can cause lupus nephritis (LN), a severe kidney inflammation.
- Type-I interferon (IFN) signature is implicated in SLE pathogenesis.
- Cyclophosphamide (CYC) is a common treatment for proliferative LN.
Purpose of the Study:
- To evaluate the longitudinal effect of cyclophosphamide (CYC) on the type-I interferon (IFN) signature in proliferative lupus nephritis (LN).
- To determine if the IFN-gene signature can predict treatment response in proliferative LN patients.
Main Methods:
- Fifty-four patients with biopsy-proven proliferative LN received high-dose (HD) or low-dose (LD) CYC.
- An interferon-gene based score (IGS) was developed and measured at baseline, 3, and 6 months.
- Treatment response was assessed at 6 months using EULAR/EDTA criteria; predictors of non-response were identified via ROC analysis.
Main Results:
- The IGS significantly decreased at 3 months in both HD and LD CYC groups, with a subsequent increase by 6 months, particularly in the LD group.
- A decrease in IGS from baseline to 3 months was observed in both clinical responders (CR) and non-responders (NR), but the magnitude of decrease (ΔIGS) was greater in CR.
- A predictive model combining an 0.81-fold decrease in IGS at 3 months with endocapillary hypercellularity and interstitial inflammation showed 83.3% sensitivity and 71.4% specificity for predicting non-response.
Conclusions:
- Cyclophosphamide treatment dynamically alters the type-I IFN signature in proliferative LN.
- A significant reduction in the IGS score within the first three months of treatment is associated with treatment response.
- Combining IGS changes with specific histopathological findings improves the prediction of non-response to CYC in proliferative LN.
Objectives:
To assess the longitudinal effect of cyclophosphamide (CYC) treatment on type-I interferon (IFN) signature in proliferative lupus nephritis (LN) and its role in predicting treatment response.
Methods:
Fifty-four biopsy proven proliferative LN patients scheduled to receive high-dose (HD) or low-dose (LD) CYC were recruited and followed up for six months. At six months, patients were classified as clinical responders (CR) or non-responders (NR) to treatment, using the EULAR/EDTA criteria. An IFN-gene based score (IGS) was developed from the mean log-transformed gene expression of MX1, OAS1, IFIT1, OASL, IFIT4, LY6E, IRF7 at baseline, three and six months. Longitudinal changes of IGS within and between groups were assessed and ΔIGS, which is the difference in IGS between baseline and three months was calculated. Independent predictors of non-response were identified and an ROC analysis was performed to evaluate their utility to predict NR.
Results:
There was a dynamic change in IGS within the HD, LD, CR, and NR groups. Compared to baseline, there was a significant decrease in IGS at three months in HD and LD groups (HD group: 2.01 to 1.14, p = .001; LD group = 2.01 to 0.81, p < .001), followed by a significant increase from three to six months in LD group (LD: 0.81 to 1.51, p = .03; HD: 1.14 to 1.54, p = .300). A decrease in IGS from baseline to three months was seen in both CR (2.13 to 0.79, p < .001) and NR groups (1.83 to 1.27, p = .046), and a significant increase from three to six months was observed only in the CR group (CR: 0.79 to 1.57, p = .006; NR: 1.27 to 1.46, p = 1). ΔIGS (baseline to three months) was higher in CR compared to NR group (-1.339 vs -0.563, p = .017). ROC analysis showed that the model comprising of 0.81 fold decrease in IGS from baseline to three months, endocapillary hypercellularity and interstitial inflammation on renal histopathology predicted non-response with a sensitivity of 83.3% and specificity of 71.4%.
Conclusion:
In proliferative LN, treated with HD or LD-CYC, combined model comprising of decrease in IGS score by 0.81 fold from baseline to three months, along with important histopathological features such as endocapillary hypercellularity and interstitial inflammation had better predictive capability for non-response.
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