Clinical, Biochemical and Epigenetic Profile of Pediatric Behçet Disease

Clinical, Biochemical and Epigenetic Profile of Pediatric Behçet Disease: Similarities and Differences From Adult Patients and Looking for Potential Biomarkers.

Behçet disease (BD) is a chronic multisystem inflammatory disorder with a relapsing-remitting course. Pediatric-onset BD is rare and characterized by marked clinical heterogeneity, frequent incomplete presentation at disease onset, and limited availability of pediatric-specific outcome measures and biomarkers.

This prospective multicenter study aims to comprehensively characterize the clinical, biochemical, genetic, and epigenetic profiles of pediatric patients with Behçet disease and to compare them with adult BD patients and healthy pediatric controls.

The study focuses on the identification of disease-associated cytokine patterns, circulating microRNA profiles, DNA methylation signatures, and genetic variants associated with monogenic autoinflammatory diseases presenting with a Behçet-like phenotype.

By integrating clinical data with multi-omic analyses, this study seeks to identify biologically and clinically meaningful patient subgroups, improve disease stratification, and explore potential biomarkers of disease activity and remission in pediatric Behçet disease.

Behçet disease is a chronic inflammatory disorder involving mucocutaneous, ocular, vascular, neurological, gastrointestinal, and musculoskeletal systems. Although the clinical manifestations of pediatric BD are largely similar to those observed in adults, pediatric cases show greater heterogeneity, higher familial aggregation, and frequent diagnostic uncertainty, particularly at early disease stages.

The etiopathogenesis of BD remains incompletely understood and is thought to involve a complex interaction between genetic predisposition, immune dysregulation, environmental triggers, and epigenetic mechanisms. Increased levels of pro-inflammatory cytokines, including interleukin (IL)-6, IL-17, and tumor necrosis factor alpha (TNF-α), as well as altered circulating microRNA and DNA methylation profiles, have been reported in adult BD patients, but data in pediatric populations are scarce.

This prospective, multicenter, case-control study will enroll pediatric and adult patients with Behçet disease and healthy pediatric controls. Clinical data will be collected longitudinally, and biological samples will be obtained during routine blood draws at predefined disease stages, including diagnosis, sustained remission, and disease flare.

The study will evaluate circulating cytokine levels, genome-wide DNA methylation profiles, circulating microRNAs, and genetic variants associated with monogenic autoinflammatory diseases that can mimic BD. Pediatric healthy controls will provide reference epigenetic and microRNA profiles for comparative analyses.

Through integrated clinical and molecular analyses, this study aims to identify disease-associated molecular signatures, characterize patient subgroups, and improve understanding of pediatric Behçet disease pathogenesis, potentially supporting future development of personalized diagnostic and therapeutic strategies.

Cases Inclusion Criteria :

• BD diagnosis according to at least one of the three sets of classification criteria [International Criteria for Behçet's Disease (ICBD), International Study Group (ISG) and Pediatric Behçet's disease criteria PEDBD)];
• Age 6 months to 70 years old.
• Written informed consent from appropriate legal representative(s), and assent from patients who have not reached the age of consent.

Cases Exclusion Criteria:

• Patients who do not meet the BD criteria OR
• Patients for whom an alternative diagnosis was not investigated and/or excluded OR
• Absence of a written informed consent.

Healthy pediatric controls:

• Patients evaluated at the Meyer Children's Hospital IRCCS Rheumatology Outpatient Clinic who are scheduled to undergo routine hematochemical tests, not for suspected inflammatory or autoimmune conditions.
• Age < 18 years, matched 1:1 by age and sex with the pediatric Behçet disease (BD) cohort.
• Absence of recent or ongoing inflammatory conditions, verified through structured medical history and physical examination.
• No clinical signs suggestive of chronic autoinflammatory or autoimmune diseases at physical examination .
• No recent prolonged use (more than 7 consecutive days within the past 4 weeks) of anti-inflammatory, glucocorticoids, immunomodulatory, therapies or antibiotics.
• Written informed consent from the legal guardian(s) and assent from minors when appropriate.

Healthy Controls Exclusion Criteria

• Diagnosis of acute or chronic inflammatory, autoimmune, or autoinflammatory conditions after the collection of structured medical history and physical examination
• Current or recent prolonged use (more than 7 consecutive days within the past 4 weeks) of anti-inflammatory drugs, gluccocorticoids, immunomodulatory agents, or antibiotics.
• Routine blood tests not performed during the visit.
• Absence of written informed consent.