Introduction

Behçet’s disease (BD) is a rare, multisystem chronic disorder with no specific histological or laboratory markers for diagnosis. Instead, clinical criteria are used to establish the diagnosis, recently updated by an international study group1–3.

Circular-RNAs (circRNAs) as type of non-coding RNAs, play significant roles in the regulation of gene expression, modulate immune responses, and control inflammation4,5. Circular RNA FUNDC1 (circRNA-FUNDC1) is derived from the FUN14 domain-containing 1 (FUNDC1) gene, which is involved in mitophagy and cellular stress responses. As a circular RNA, it forms a stable, covalently closed structure, making it resistant to degradation6,7.

FUNDC1 is an intracellular mitochondrial outer membrane protein expressed in immune and vascular-relevant cells, including macrophages, T lymphocytes, and endothelial cells, where it regulates mitophagy under conditions of hypoxia and inflammatory stimulation8,9.

Under oxidative stress and inflammation, FUNDC1-dependent mitophagy reduces mitochondrial damage and reactive oxygen species (ROS) accumulation, thereby modulating downstream inflammatory signaling pathways that contribute to cytokine production and vascular inflammation relevant to Behçet’s disease8,10,11.

CircRNAs can act as sponges for microRNAs, influencing the levels of miRNAs that regulate pro-inflammatory signaling molecules like and interleukin 6 and tumor necrosis factor alpha4,5.

Tumor necrosis factor-alpha (TNF-α) is an essential pro-inflammatory cytokine that contributes to immune regulation and inflammation. It is produced by T-cells and macrophages in response to infections and autoimmune triggers, driving tissue damage and immune activation. Cytokines such as TNF-α, showed a crucial function in the development of autoimmune diseases as well as the therapeutic potential of cytokine-targeted therapies. In addition, TNF inhibitors are widely used to manage these conditions by reducing inflammation and improving symptoms12–14.

Currently, to the best of our knowledge, there are no direct studies or evidence linking circRNA-FUNDC1 in combination with TNF-α together specifically to Behçet’s disease. However, circRNA-FUNDC1 can regulate inflammation by serving as a competitive endogenous RNA (ceRNA), binding to microRNAs in a sponge-like manner that modulate proinflammatory signaling pathways6,7.

The core purpose of this study is to evaluate the levels of circRNA-FUNDC1 and TNF-α in the serum of BD patients and compare them accordingly to healthy individuals, aiming to analyze the potential role of these serum markers in BD.