A recent study published in Clinical and Experimental Rheumatology has identified soluble triggering receptor expressed on myeloid cells 2 (sTREM2) as a promising biomarker for predicting the development of neuropsychiatric systemic lupus erythematosus (NPSLE). Researchers also developed a novel nomogram incorporating this biomarker to aid clinical prediction.
The study, which enrolled 80 patients with NPSLE and 240 matched controls with systemic lupus erythematosus (SLE) but without neuropsychiatric events, sought to identify biomarkers that could help determine which patients are most at risk of developing neuropsychiatric manifestations. Through bioinformatics analysis, TREM2 emerged as an upregulated gene in NPSLE patients, linked to several pathological pathways associated with central nervous system involvement in lupus.
Results showed that sTREM2 levels were significantly elevated in both serum and cerebrospinal fluid of NPSLE patients compared with controls. serum sTREM2 concentrations correlated with disease severity and neuropsychiatric status. Alongside sTREM2, other predictors for NPSLE development included higher SLE Disease Activity Index (SLEDAI) scores, increased Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SDI) scores, prolonged activated partial thromboplastin time (APTT), and elevated B cell counts.
TREM2 is an innate immune receptor predominantly expressed on macrophages, dendritic cells, and microglia within the central nervous system. It plays a critical role in regulating microglial functions such as phagocytosis, survival, proliferation, and metabolic activity, particularly in response to tissue injury, beta amyloid deposition, demyelination, or apoptotic cell death. Genetic variations in TREM2 have been linked to several neurological conditions, including Nasu Hakola disease, a rare presenile dementia with bone cysts, as well as increased susceptibility to Alzheimer’s disease and frontotemporal dementia. In its soluble form, sTREM2 can be detected in plasma and cerebrospinal fluid, and accumulating evidence supports its potential as both a disease biomarker and a therapeutic target.
The researchers concluded that sTREM2 offers strong potential as a diagnostic biomarker for NPSLE. The predictive nomogram incorporating serum sTREM2 levels demonstrated effectiveness in distinguishing NPSLE from non-NPSLE patients, providing clinicians with a potential tool to identify those at higher risk. Early recognition of at-risk patients could support timely intervention and improve outcomes for individuals living with lupus.
References
- Wang X, Tang J, Lu F, Zhang X, Yao J, Gu P, Sun M, Wang Y. A novel nomogram based on the identification of sTREM2 as a biomarker to predict developing neuropsychiatric systemic lupus erythematosus in lupus patients. Clin Exp Rheumatol. 2025 Sep;43(9):1582-1592.
- Filipello F, Goldsbury C, You SF, Locca A, Karch CM, Piccio L. Soluble TREM2: Innocent bystander or active player in neurological diseases? Neurobiol Dis. 2022 Apr;165:105630.