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Interferon Regulatory Factor 4: An Alternative Marker for Plasma Cells in Daratumumab-Treated Patients With Multiple
Suwen Yang1,2, Qianwen Hu1,2, Xiaofen Wang1
1Clinical Laboratory, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China.
Introduction:
Anti-CD38 therapeutic modalities (e.g., daratumumab) can impede classical CD38 and CD138 gating use for plasma cell (PC) detection in multiple myeloma (MM) patients with minimal residual disease (MRD). We assessed the applicability of CD229, CD269, and interferon regulatory factor (IRF-4) for PC detection in MM MRD patients.
Methods:
Bone marrow samples were collected from patients with MM. Through multiparameter flow cytometry, we evaluated the suitability of CD229, CD269, and IRF-4 for distinguishing PCs from other hematopoietic cells and compared their expression pattern on normal PCs (nPCs) and aberrant PCs (aPCs). We also assessed IRF-4 expression stability after sample storage under different conditions. A 10-color MRD antibody panel was used to determine whether IRF-4 is an alternative primary PC-gating marker for MM MRD assessment.
Results:
IRF-4 was expressed specifically on all PCs; its mean fluorescence intensity (MFI) was highest on PCs among all hematopoietic cells. This MFI did not decrease even after sample storage at 4°C or 25°C for 72 h. In all 42 MRD assessment samples, except for samples (n = 10) with no PCs, the use of IRF-4 enabled accurate nPC (n = 12), aPC (n = 13), and nPC + aPC (n = 7) identification. Even samples from daratumumab-treated patients had high IRF-4 MFI, with no difference between pre-treatment and post-treatment (n = 7; p = 0.610).
Conclusions:
IRF-4 demonstrates high MFI on PCs, and it is not expressed on other leukocytes. In MM patients with MRD, daratumumab treatment does not affect IRF-4 expression. IRF-4 is a promising marker for PC identification in MRD assessment of MM patients undergoing anti-CD38 therapy.
Insights
Interferon regulatory factor 4 (IRF-4) is a reliable marker for detecting plasma cells (PCs) in multiple myeloma (MM) minimal residual disease (MRD) assessment. IRF-4 remains effective even after anti-CD38 therapy, offering a viable alternative for PC identification.
Area of Science:
- Hematology
- Immunology
- Oncology
Background:
- Anti-CD38 therapies, like daratumumab, complicate plasma cell (PC) detection in multiple myeloma (MM) minimal residual disease (MRD) assessment by interfering with standard CD38 and CD138 markers.
- Alternative markers are needed to accurately identify PCs in MM patients undergoing anti-CD38 treatment for MRD monitoring.
Purpose of the Study:
- To evaluate the utility of CD229, CD269, and interferon regulatory factor 4 (IRF-4) as alternative markers for PC detection in MM patients with MRD.
- To assess the stability and specificity of IRF-4 expression on PCs, including in samples from patients treated with daratumumab.
Main Methods:
- Multiparameter flow cytometry was used to analyze bone marrow samples from MM patients.
- The expression patterns of CD229, CD269, and IRF-4 were compared between normal PCs (nPCs) and aberrant PCs (aPCs).
- IRF-4 expression stability was tested under various sample storage conditions, and its efficacy as a primary PC-gating marker in a 10-color MRD panel was assessed.
Main Results:
- IRF-4 showed specific and high mean fluorescence intensity (MFI) on all PCs, with no expression on other leukocytes.
- IRF-4 MFI remained stable even after 72 hours of sample storage at 4°C or 25°C.
- IRF-4 accurately identified PCs (nPCs, aPCs, or combined) in 32 out of 42 MRD assessment samples and was unaffected by daratumumab treatment.
Conclusions:
- IRF-4 is a highly specific marker for PCs with stable expression, unaffected by storage conditions or anti-CD38 therapy.
- IRF-4 serves as a promising alternative primary marker for PC identification in MM MRD assessment, particularly for patients receiving anti-CD38 treatments.
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