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

Eman Ali Abdallah; Khaled Mohamed Amin Elzorkany; Dina Salem; Asmaa Elshemy; Manar Dawoud; Noha Khirat; Azza Gomaa; Dina Alsharaky

doi:10.1177/09612033251349458

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

Lupus. 2025 Aug;34(9):932-942. doi: 10.1177/09612033251349458. Epub 2025 Jun 19.

Authors

Eman Ali Abdallah¹, Khaled Mohamed Amin Elzorkany², Dina Salem¹, Asmaa Elshemy³, Manar Dawoud⁴, Noha Khirat⁴, Azza Gomaa⁵, Dina Alsharaky¹

Affiliations

¹ Rheumatology, Physical Medicine and Rehabilitation Department, Faculty of Medicine, Menoufia University, Shiben Elkom, Egypt.
² Internal Medicine Department, College of Medicine, King Faisal University, Alhasa, Saudi Arabia.
³ Clinical Pathology Department, Faculty of Medicine, Menoufia University, Shiben Elkom, Egypt.
⁴ Ophthalmology Department, Faculty of Medicine, Menoufia University, Shiben Elkom, Egypt.
⁵ Internal Medicine Department, Nephrology Unit, Faculty of Medicine, Menoufia University, Shiben Elkom, Egypt.

PMID: 40536502
DOI: 10.1177/09612033251349458

Abstract

BackgroundSystemic 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.ObjectiveTo evaluate SIRT1 levels and study potential association with keratoconjunctivitis sicca (KCS) in SLE patients in relation to disease activity.MethodsA 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.ResultsPatients 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.ConclusionsSerum 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.

Keywords: SLE; biomarker; disease activity; dry eye disease; lupus; sirtuin-1.

MeSH terms

Adult
Biomarkers / blood
Case-Control Studies
Cross-Sectional Studies
Enzyme-Linked Immunosorbent Assay
Female
Humans
Keratoconjunctivitis Sicca* / blood
Keratoconjunctivitis Sicca* / diagnosis
Keratoconjunctivitis Sicca* / epidemiology
Keratoconjunctivitis Sicca* / etiology
Lupus Erythematosus, Systemic* / blood
Lupus Erythematosus, Systemic* / complications
Male
Middle Aged
Severity of Illness Index
Sirtuin 1* / blood
Young Adult

Substances

Sirtuin 1
SIRT1 protein, human
Biomarkers