YTHDF2 Level in Peripheral Blood Mononuclear Cells Correlates with Pathological Activity Index in Patients with Lupus Nephritis

Background: The therapeutic decision of Lupus nephritis (LN) need making based on pathological classification including activity index (AI) evaluated on renal biopsy. Some biopsy contraindication restricts the pathological diagnosis of LN. YTHDF2 (YTH N6-methyladenosine RNA binding protein 2) has been reported differential expression in SLE. However, the clinical significance of YTHDF2 levels in peripheral blood mononuclear cells (PBMC) of LN pathological AI scoring has not been reported. Methods: This study enrolled 34 patients proven by renal biopsy as LN class III/IV ± V . We grouping patients based on AI score including 25 cases with AI≥8 and 9 cases with AI<8. PBMC were separated from whole blood in these 34 patients. Total RNA was extracted for quantitative analysis of YTHDF2 mRNA levels by RT-qPCR. Statistical analysis was performed as follows: The Shapiro-Wilk test was used to assess data distribution characteristics. Normally distributed continuous variables were expressed as mean ± standard deviation (X ± S), while non-normally distributed variables were presented as median (interquartile range). Intergroup differences were analyzed using t-tests, Mann-Whitney U tests, or chi-square tests as appropriate. The diagnostic performance of YTHDF2 in predicting LN pathological activity was evaluated by receiver operating characteristic (ROC) curve analysis. Furthermore, the net reclassification improvement index (NRI) was calculated to assess the incremental predictive value of YTHDF2 for LN activity index. A two-tailed P-value <0.05 was considered statistically significant. Results: A differential YTHDF2 expression showed between patients with high and low AI score. LN patients with AI≥8 exhibited significantly increased YTHDF2 levels in PBMCs compared to those patients with AI<8 on pathological diagnosis. YTHDF2 in PBMC to differentiate high AI from low AI exhibited a high-performance power.ROC analysis demonstrated that YTHDF2 effectively discriminated high-activity LN (AI≥8) with an AUC of 0.760 (95% CI: 0.556–0.964, P=0.022). After combining with traditional anti-double strand DNA antibody, the differential diagnostic accuracy for high AI and low AI for LN increased significantly (NRI=0.516, P=0.003). Conclusion: YTHDF2 expression in PBMC might serve as potential invasive novel which can mirror pathological activity index for lupus nephritis. Funding: Government Support – Non-U.S.