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Published on: February 23, 2024
Biomarker panel increases accuracy for identification of an MS relapse beyond sNfL
Saurabh Gawde1, Agnieshka Agasing1, Neal Bhatt2
1Department of Arthritis and Clinical Immunology Research, Oklahoma Medical Research Foundation, Oklahoma City, OK, USA; Department of Microbiology and Immunology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.
Background:
For relapsing-remitting multiple sclerosis (RRMS), there is a need for biomarker development beyond clinical manifestations and MRI. Soluble neurofilament light chain (sNfL) has emerged as a biomarker for inflammatory activity in RRMS. However, there are limitations to the accuracy of sNfL in identifying relapses. Here, we sought to identify a panel of biomarkers that would increase the precision of distinguishing patients in relapse compared to sNfL alone.
Methods:
We used a multiplex approach to measure levels of 724 blood proteins in two distinct RRMS cohorts. Multiple t-tests with covariate correction determined biomarkers that were differentially regulated in relapse and remission. Logistic regression models determined the accuracy of biomarkers to distinguish relapses from remission.
Results:
The discovery cohort identified 37 proteins differentially abundant in active RRMS relapse compared to remission. The verification cohort confirmed four proteins, including sNfL, were altered in active RRMS relapse compared to remission. Logistic regression showed that the 4-protein panel identified active relapse with higher accuracy (AUC = 0.87) than sNfL alone (AUC = 0.69).
Conclusion:
Our studies confirmed that sNfL is elevated during relapses in RRMS patients. Furthermore, we identified three other blood proteins, uPA, hK8 and DSG3 that were altered during relapse. Together, these four biomarkers could be used to monitor disease activity in RRMS patients.
Insights
A new biomarker panel improves relapse detection in relapsing-remitting multiple sclerosis (RRMS) beyond soluble neurofilament light chain (sNfL) alone. This four-protein signature offers more precise monitoring of disease activity.
Area of Science:
- Neuroimmunology
- Biomarker Discovery
- Multiple Sclerosis Research
Background:
- Relapsing-remitting multiple sclerosis (RRMS) requires improved biomarkers beyond clinical and MRI assessments.
- Soluble neurofilament light chain (sNfL) shows promise for tracking RRMS inflammatory activity but has limitations in accurately identifying relapses.
- Enhanced precision is needed to distinguish RRMS relapse from remission states.
Purpose of the Study:
- To identify a panel of blood protein biomarkers for increased accuracy in distinguishing RRMS relapse from remission.
- To evaluate the diagnostic performance of a multi-biomarker panel compared to sNfL alone.
Main Methods:
- A multiplex proteomic approach was employed to analyze 724 blood proteins in two independent RRMS cohorts.
- Statistical analyses, including t-tests with covariate correction, identified differentially regulated proteins during relapse and remission.
- Logistic regression models assessed the accuracy of individual biomarkers and panels in differentiating relapse from remission.
Main Results:
- The discovery cohort revealed 37 differentially abundant proteins in active RRMS relapse versus remission.
- The verification cohort confirmed four proteins, including sNfL, were significantly altered during active RRMS relapse.
- A four-protein panel demonstrated superior accuracy (AUC = 0.87) in identifying active relapse compared to sNfL alone (AUC = 0.69).
Conclusions:
- sNfL levels are confirmed to be elevated during RRMS relapses.
- Three additional blood proteins—uPA, hK8, and DSG3—were identified as altered during RRMS relapse.
- The combined four-biomarker panel offers a more precise tool for monitoring RRMS disease activity.
