Evaluation of high mobility group box 1 protein as an inflamation marker in patients with familial mediterranean fever

Introduction and Objectives: Familial Mediterranean Fever (FMF) is an autoinflammatory disease that commonly presents with fever, peritonitis, pleuritis, synovitis, and less commonly with pericarditis. Several recent studies reported ongoing inflammation in the attack-free period of patients with FMF. Other studies revealed that some proteins show an inflammatory response after translocation to an extracellular environment through cellular damage. These proteins are known as Damage-Associated Molecular Patterns (DAMPs); they carry out daily physiological cell functions and induce a strong inflammatory response after translocation to an extracellular area after cell damage has occurred. High mobility group box protein (HMGB1) is a frequently-investigated DAMPs molecule, with a strong diagnostic and prognostic role for several chronic inflammatory diseases. Our aim was to discover HMGB1's role in FMF. Patients and Method: Sixty consecutive patients with FMF that were followed in the Pediatric Nephrology department of our institute were included in this study. Sixty healthy children were also included as the control group. Demographic data of patients and their parents, including the patients' genetic analyses, and demographic data of controls were recorded. Blood samples were obtained from patients and controls for HMGB1 analysis. Laboratory analysis of patients included CRP, sedimentation, blood count, fibrinogen, creatine kinase, AST, ALT, creatinine, and microalbumin/creatinine from urine samples were recorded as well. Findings: Fifty-seven patients with FMF (27 female / 32 male) and 60 healthy children (30 female / 30 male) were included in this study. The median age of patients and healthy controls was 123 months (min-max: 20-220). Thirty-three patients (57.9%) in the FMF group had a history of disease in their family, while there were consanguineous marriages in 6 of the patients' parents (10.5%). Furthermore, 65% of patients came from the west Blacksea region and west-middle Anatolian region. The median follow-up of patients with FMF diagnosis was 5 years (min-max: 1-12 years). The most frequent patient mutation was M694V (78%). All patients were on colchicine treatment, with the median dose being 1 mg/day (min-max: 0.5 mg-1.5 mg). Age, sex, and body weight were similar among both patients and controls. Patients' HMGB1 levels were significantly higher when compared to controls (p = 0.001). There was a significant positive correlation between HMGB1 and red cell distribution width (RDW), including neutrophil to lymphocyte ratio. No significant relation was observed between patient mutations and HMGB1 and HMGB1 levels were similar during both the attack and the attack-free period of patients. Conclusion: This study demonstrated that HMGB1 levels in patients with FMF are significantly higher compared to healthy controls, while these levels are not influenced by the period of the disease. Our study finds that subclinical inflammation persists in patients with FMF in the attack-free period. Further comprehensive studies, with a greater number of patients, are necessary to thoroughly examine this issue.