CXCL9 emerges as a promising biomarker for primary Sjögren’s syndrome with extra-glandular manifestations

In a recent publication featured in Arthritis Research & Therapy, CXCL9 emerges as a pivotal biomarker for primary Sjögren’s syndrome (pSS), demonstrating remarkable efficacy in distinguishing between pSS patients with and without extra-glandular manifestations (EGM). 

Hong and colleagues utilized advanced RNA sequencing techniques to analyze gene expression profiles in the minor salivary glands (MSG) of 63 patients diagnosed with pSS and 12 non-pSS individuals. The comparative analysis revealed 725 differentially expressed genes (DEGs) between the pSS and non-pSS groups, while 727 DEGs were identified between pSS patients with EGM and those without EGM. Notably, the expression levels of CXCL9 were significantly elevated in both pSS patients and those with pSS-EGM compared to the control group. In comparison to the non-pSS group, pSS patients exhibited markedly higher expression of the CXCL9 gene in the MSG, accompanied by elevated CXCL9 protein levels in their plasma (P < 0.001). Moreover, the expression of the CXCL9 gene and levels of CXCL9 protein were significantly elevated in pSS patients with EGM and those possessing SSA antibodies. 

Further analysis revealed a correlation between CXCL9 gene expression and the EULAR Sjögren’s Syndrome Disease Activity Index (ESSDAI), as well as with IgG levels and ESR. Concurrently, protein levels of CXCL9 were found to be correlated with IgG levels and ESSDAI. These findings underscore the potential of CXCL9 as a crucial marker in understanding the pathogenesis and clinical manifestations of pSS. CXCL9, a chemokine protein, engages with its receptor, CXCR3, orchestrating the recruitment of T cells, natural killer cells, and macrophages to the inflamed site. The interferon-gamma-induced form of CXCL9, alternatively termed MIG (monokine induced by interferon gamma), is implicated in the onset of various autoimmune diseases, including pSS. Numerous investigations have documented increased levels of CXCL9 in the exocrine gland of individuals diagnosed with pSS. 

The results of this study affirm the increased presence of CXCL9 in individuals with pSS, particularly in those exhibiting EGM and possessing SSA antibodies. Increased expression of CXCL9 emerges as a potential valuable biomarker for gauging disease severity, implying its substantial influence on disease progression. However, further research is imperative to validate these noteworthy findings. 


Hong J, Cheng H, Wang P, Wu Y, Lu S, Zhou Y, et al. CXCL9 may serve as a potential biomarker for primary Sjögren’s syndrome with extra-glandular manifestations. Arthritis Res Ther. 2024 Jan 17;26(1):26.