Expression of herpes simplex virus-related genes in peripheral blood leukocytes of patients with behçet’s disease: a case-control study

Abstract

Abstract Behçet’s disease is a chronic, relapsing multisystem inflammatory disorder characterized by recurrent oral and genital ulcerations, ocular inflammation, cutaneous lesions, and variable involvement of the vascular, neurological, and gastrointestinal systems. Although its precise etiology remains incompletely understood, accumulating evidence indicates that the disease arises from a complex interplay between genetic susceptibility, immune dysregulation, and environmental triggers. Among the proposed infectious agents, herpes simplex virus (HSV) has attracted considerable attention because of its capacity to induce persistent immune activation, molecular mimicry, and chronic inflammatory responses. Accordingly, the present study aimed to evaluate the expression profiles of HSV-related genes (UL29, UL18, UL46, and UL47) in peripheral blood leukocytes of patients with Behçet’s disease to clarify the potential contribution of HSV infection to disease pathogenesis and immune-mediated inflammatory mechanisms. In this case-control study, 40 patients with BD and 40 healthy individuals were included as the control group. Blood samples were collected from all participants. Total RNA was extracted from peripheral blood leukocytes, followed by cDNA synthesis. The expression levels of UL29, UL18, UL46, and UL47 genes were quantified using RT-qPCR. Receiver operating characteristic (ROC) curve analysis was performed to assess the diagnostic potential of the studied genes. Statistical analyses were conducted using GraphPad Prism and SPSS software (P-value ≤ 0.05). The expression of HSV-related genes was significantly higher in BD patients compared to healthy controls. After Bonferroni correction for multiple comparisons, UL29 remained significantly upregulated (4.5-fold, adjusted p = 0.012), while UL46 (3.7-fold, adjusted p = 0.060), UL18 (2.0-fold, adjusted p = 0.152), and UL47 (2.25-fold, p = 0.12) did not reach statistical significance. ROC curve analysis demonstrated strong diagnostic potential for UL29 (AUC = 0.90, sensitivity 80%, specificity 92.5%), UL46 (AUC = 0.86, sensitivity 87%, specificity 77.5%), and UL18 (AUC = 0.80, sensitivity 85%, specificity 72.5%). Overall, UL29, UL46, and UL18 showed promising potential as biomarkers for distinguishing BD patients from healthy individuals. Increased expression of UL29, UL46, and UL18 is associated with BD, and these genes, particularly UL29, show promising potential as diagnostic biomarkers. Further validation studies are needed.