Increased expression of TRIM69 in peripheral blood from systemic lupus erythematosus and its clinical significance

Several proteins in the tripartite-motif (TRIM) family are associated with the development of systemic lupus erythematosus (SLE), but the role of TRIM69 in SLE is still poorly elaborated.

We enrolled 72 patients with SLE, 62 healthy controls (HC), and 65 patients with rheumatoid arthritis (RA). TRIM69 mRNA expression in whole blood was measured by RT‑qPCR; serum TRIM69 levels were detected by ELISA. Clinical correlations were analysed, and ROC curves were constructed. Univariate and multivariate regression analyses were performed with multiple testing adjustment using the false discovery rate method. A predictive model based on serum TRIM69, haemoglobin (HGB), and neutrophil-to-lymphocyte ratio (NLR) was developed and internally validated via 5‑fold cross‑validation; then it was tested in an independent cohort. Gene set enrichment analysis (GSEA) and immune cell infiltration analyses were used to explore the role of TRIM69 in the pathogenesis of SLE.

TRIM69 expression was significantly elevated in SLE patients compared to HCs and RA groups, and was strongly correlated with clinical features. Serum TRIM69 alone showed discriminatory ability for SLE in receiver operating characteristic (ROC) analysis. A predictive model combining serum TRIM69, HGB, and NLR effectively distinguished SLE from HC. The model achieved a training area under the curve (AUC) of 0.941(sensitivity = 93.55%, specificity = 81.94%). Cross-validation demonstrated an overall accuracy of 86.55% with a Kappa value of 0.731. This model performed consistently in an independent validation cohort, with an AUC of 0.931(sensitivity = 87.50%, specificity = 87.50%). Additionally, the model correlated with SLE disease activity, as measured by established activity scores, and differentiated SLE from RA and HC combined, with an AUC of 0.805.

The study suggested that the elevated TRIM69 may play a role in SLE pathogenesis and predictive model based on serum TRIM69 levels, HGB, and NLR act as bioindicator for forecast and progression of diseases.