Anti-PRMT5 antibodies, a new biomarker for the early diagnosis of systemic sclerosis

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Rheumatologists and researchers have long sought better biomarkers for diagnosing and predicting the progression of systemic sclerosis (SSc). A recent study has identified anti-protein arginine methyltransferase 5 (PRMT5) antibodies as a promising new biomarker, offering significant potential in the early diagnosis and monitoring of SSc. 

The study revealed a significant increase in anti-PRMT5 antibodies among SSc patients, with high diagnostic accuracy in distinguishing them from healthy individuals and those with other autoimmune diseases like lupus and Sjögren’s syndrome, showing an AUC of 0.900 to 0.988. Validation in a second cohort confirmed that 31.11% of SSc patients were seropositive for anti-PRMT5 antibodies, correlating with disease progression, particularly in skin and lung involvement. Additionally, mice immunized with PRMT5 developed SSc-like symptoms, including inflammation and fibrosis, further highlighting the role of PRMT5 in SSc pathogenesis. 

PRMT5 is a type II enzyme from the methyltransferase family, responsible for catalyzing symmetric dimethylation on both histones and non-histone proteins. PRMT5 plays a crucial role in various biological processes, from gene regulation to human development. As part of the broader PRMT family, it contributes to numerous cellular functions, particularly the regulation of the inflammatory response. This regulation is key in the onset of various inflammation-related and autoimmune diseases, including rheumatoid arthritis, Alzheimer’s disease, systemic lupus erythematosus, asthma, atherosclerosis, cancer, and ischemic heart disease. PRMT5 is critical in modulating the activation of the inflammatory process. 

Dong et al.  explored the role of PRMT5 in the development of osteoarthritis (OA) and found that PRMT5 is significantly upregulated in OA cartilage. Overexpression of PRMT5 in human chondrocytes resulted in cartilage degradation through increased production of matrix-degrading enzymes MMP-3 and MMP-13, along with activation of the MAPK and NF-κB signaling pathways. Inhibition of PRMT5 with the compound EPZ effectively reduced these harmful effects in both human chondrocytes and a mouse OA model, where it protected cartilage from damage. These findings highlight PRMT5 as a key driver of OA pathogenesis and suggest that targeting PRMT5 with inhibitors like EPZ could offer a promising therapeutic strategy for OA. 

Anti-PRMT5 antibodies show significant promise as a novel biomarker for SSc, offering high diagnostic accuracy and correlation with disease progression, particularly in skin and lung involvement. The findings suggest that PRMT5 plays a key role in the pathogenesis of SSc and potentially other autoimmune diseases. Furthermore, research on involvement of PRMT5 in OA highlights its broader impact on inflammation and disease progression, making PRMT5 a potential therapeutic target in both SSc and OA.  

References 

  1. Liang M, Wang L, Tian X, Wang K, Zhu X, Huang L, Li Q, Ye W, Chen C, Yang H, Wu W, Chen X, Zhu X, Xue Y, Wan W, Wu Y, Lu L, Wang J, Zou H, Ying T, Zhou F. Identification and validation of anti-protein arginine methyltransferase 5 (PRMT5) antibody as a novel biomarker for systemic sclerosis (SSc). Ann Rheum Dis. 2024 Aug 27;83(9):1144-1155. 
  2. Tan B, Liu Q, Yang L, Yang Y, Liu D, Liu L, Meng F. Low expression of PRMT5 in peripheral blood may serve as a potential independent risk factor in assessments of the risk of stable CAD and AMI. BMC Cardiovasc Disord. 2019 Jan 31;19(1):31. 
  3. Dong Y, Wang P, Yang Y, Huang J, Dai Z, Zheng W, Li Z, Yao Z, Zhang H, Zheng J. PRMT5 inhibition attenuates cartilage degradation by reducing MAPK and NF-κB signaling. Arthritis Res Ther. 2020 Sep 4;22(1):201. 
  4. Zhu H, Zheng J, Zhou Y, Wu T, Zhu T. PRMT5 participates in B cell overactivation in patients with primary Sjogren’s syndrome (pSS) through RSAD2-mediated NF-κB signaling. Immun Inflamm Dis. 2023 Dec;11(12):e1102.