Mendelian randomization analysis suggests no associations of herpes simplex virus infections with systemic lupus erythematosus

Abstract

Systemic lupus erythematosus (SLE) characterized by immune dysfunction is possibly more vulnerable to herpes simplex virus (HSV) infection. The infection has been intensively considered a common onset and exacerbation of SLE. This study is aimed at elucidating the causal association between SLE and HSV. A bidirectional two‐sample Mendelian Randomization (TSMR) analysis was systematically conducted to explore the causal effect of SLE and HSV on each other. The causality was estimated by inverse variance weighted (IVW), MR‐Egger and weighted median methods based on the summary‐level genome‐wide association studies (GWAS) data from a publicly available database. Genetically proxied HSV infection exhibited no causal association with SLE in the forward MR analysis using IVW method (odds ratio [OR] = 0.987; 95% confidence interval [CI]: 0.891–1.093; p = 0.798), nor did HSV‐1 IgG (OR = 1.241; 95% CI: 0.874–1.762; p = 0.227) and HSV‐2 IgG (OR = 0.934; 95% CI: 0.821–1.062; p = 0.297). Similar null results with HSV infection (OR = 1.021; 95% CI: 0.986–1.057; p = 0.245), HSV‐1 IgG (OR = 1.003; 95% CI: 0.982–1.024; p = 0.788) and HSV‐2 IgG (OR = 1.034; 95% CI: 0.991–1.080; p = 0.121) were observed in the reverse MR where SLE served as the exposure. Our study demonstrated no causal association between the genetically predicted HSV and SLE.

Herpes simplex virus and SLE: Though uncommon yet with significant implications

“…Interestingly, other members of the HHVs were directly and indirectly linked to SLE including Herpes Simplex Virus (HSV). In contrast to the findings presented by Chang et al 3 ; Reis and colleagues illustrated a significant importance of both primary and reactivation of HHVs in patients with SLE. 9 By enrolling 71 SLE patients classified into active and non-active disease, serum samples were evaluated by PCR for the detection of HHVs including HSV-1 and HSV-2.…”

“…2 However, it shows the strong bond between infection and autoimmunity. Subsequently, with a deep interest in the field, we analyzed the article of Chang et al 3 concluding that there is no…”

Immunopathology of herpes simplex virus‐associated neuroinflammation: Unveiling the mysteries

“…Ultimately, the outcomes of their study do not indicate any substantial associations between HSV infections and the likelihood of SLE occurrence. This finding introduces a valuable aspect to understanding potential interrelationships between viral infections and autoimmune conditions like SLE 252 …”