Sirtuin-1 in systemic lupus erythematosus: Frequency of keratoconjunctivitis sicca and relation to disease activity

• Published in: Lupus Vol. 34; no. 9; pp. 932 - 942
• Main Authors: Abdallah, Eman Ali, Elzorkany, Khaled Mohamed Amin, Salem, Dina, Elshemy, Asmaa, Dawoud, Manar, Khirat, Noha, Gomaa, Azza, Alsharaky, Dina
• Format: Journal Article
• Language: English
• Published: London, England SAGE Publications 01.08.2025; Sage Publications Ltd
• Subjects: Adult; Autoantibodies; Biomarkers - blood; Case-Control Studies; Cross-Sectional Studies; Enzyme-Linked Immunosorbent Assay; Female; Humans; Keratoconjunctivitis; Keratoconjunctivitis Sicca - blood; Keratoconjunctivitis Sicca - diagnosis; Keratoconjunctivitis Sicca - epidemiology; Keratoconjunctivitis Sicca - etiology; Leukocytes; Lupus; Lupus Erythematosus, Systemic - blood; Lupus Erythematosus, Systemic - complications; Male; Middle Aged; Pathophysiology; Platelets; Severity of Illness Index; SIRT1 protein; Sirtuin 1 - blood; Systemic lupus erythematosus; Therapeutic targets; Young Adult; disease activity; dry eye disease; biomarker; sirtuin-1; SLE; lupus
• ISSN: 0961-2033; 1477-0962; 1477-0962
• DOI: 10.1177/09612033251349458

Background Systemic lupus erythematosus (SLE) is a complex autoimmune disorder characterized by the production of various autoantibodies and involvement of multiple organ systems, including the eyes. Growing evidence suggests that dysregulation of proteins from the sirtuin family, particularly sirtuin-1 (SIRT1), may play a crucial role in the pathophysiology of SLE, despite its incomplete understanding. Objective To evaluate SIRT1 levels and study potential association with keratoconjunctivitis sicca (KCS) in SLE patients in relation to disease activity. Methods A cross-sectional study was conducted on 42 SLE adult patients and 42 healthy controls. Serum SIRT1 levels were measured using enzyme-linked immunosorbent assay. Disease activity was assessed using the SLE Disease Activity Index (SLEDAI) score. Correlations between SIRT1 levels, KCS and disease activity, were analyzed. Results Patients with SLE had significantly higher SIRT1 levels than healthy controls (p <  .001). SIRT1 was strongly correlated with disease activity (r = 0.958, p < .001), and albuminuria (r = 0.719, p < .001). Negative correlations were observed between SIRT1 levels and C3 (r = −0.843, p < .001), C4 (r = −0.861, p < .001), white blood cell count (r = −0.616, p < .001) and platelet count (r = −0.534, p < .001). Additionally, Patients with SLE who presented with KCS had significantly higher SIRT1 levels than those without (p < .001). SIRT1 exhibited exceptional diagnostic efficacy in differentiating between Patients with SLE and control subjects, with an AUC of 1 (p < .001) and in identifying KCS in SLE patients, with an AUC of 0.989 (p < .001). The multivariable regression model indicated that a lower platelets count (p = .034; OR −0.014; 95% CI −0.026 to −0.001) and high SIRT1 levels (p < .001; OR 0.838; 95% CI 0.678–0.998) were independent predictors of disease activity. Conclusions Serum SIRT1 levels were significantly elevated in patients with SLE and correlated with the presence of KCS and disease activity. SIRT1 may serve as a potential biomarker of eye involvement in SLE, the disease pathogenesis and severity, and its modulation could offer a therapeutic target for the disease.