Rille Pullerits1, Hanna Schierbeck2, Karin Uibo3, Hille Liivamägi4, Sirje Tarraste3, Tiina Talvik5, Erik Sundberg2, Chris Pruunsild6. 1. Department of Rheumatology and Inflammation Research, Institute of Medicine, Sahlgrenska Academy at the University of Gothenburg, Box 480, Gothenburg 40530, Sweden; Department of Clinical Immunology, Sahlgrenska University Hospital, Gothenburg, Sweden. Electronic address: rille.pullerits@rheuma.gu.se. 2. Department of Women's and Children's Health, Pediatric Unit, Karolinska Institute, Stockholm, Sweden. 3. Tallinn Children's Hospital Rheumatology Unit, Tallinn, Estonia. 4. Department of Pediatrics, Tartu University, Tartu, Estonia. 5. Department of Pediatric Neurology, Children's Clinic, Tartu University Hospital, Tartu, Estonia; Department of Pediatrics, Tartu University, Tartu, Estonia. 6. Department of Pediatrics, Tartu University, Tartu, Estonia; Department of General Pediatrics, Children's Clinic, Tartu University Hospital, Tartu, Estonia.
Abstract
OBJECTIVE: High mobility group box protein 1 (HMGB1) is an important pro-inflammatory mediator in adult rheumatoid arthritis. The diagnostic utility of HMGB1 in Juvenile Idiopathic Arthritis (JIA) is still unclear. The aim was to examine whether serum HMGB1 levels are associated with inflammation, radiological disease progression, and long-term prognosis in JIA. METHODS: We included 131 children with JIA from a population-based prevalence study; 38 of them were prospectively followed up for 10 years. Clinical and laboratory disease characteristics at study entry and after 10 years as well as radiological progression over 10 years were recorded. HMGB1 levels were analyzed by an ELISA. RESULTS: The HMGB1 levels were similar in children with different JIA subgroups and in children with established (53%) or newly diagnosed (47%) disease. HMGB1 levels did not differ between groups at entry into the study or at 10 years, by sex, or by the presence or absence of RF or ANA antibodies. HMGB1 levels at the study entry correlated with HMGB1 levels at 10 years and with blood neutrophil count. Most importantly, children with destructive arthritis at 10 years had a tendency toward higher HMGB1 levels at study entry (median 1.2 vs 0.6ng/ml, ns) and displayed 4-fold higher circulating HMGB1 levels (median 3.4 vs 0.8ng/ml, p = 0.0014) than children without radiological destructions. CONCLUSIONS: Our results suggest that HMGB1 is a marker of inflammatory activity in children with JIA. Higher serum HMGB1 levels are related to more destructive JIA and could be used as a negative prognostic marker at the disease start. TRIAL REGISTRATION: Clinicaltrials.gov NCT01905319. Registered July 16, 2013.
OBJECTIVE:High mobility group box protein 1 (HMGB1) is an important pro-inflammatory mediator in adult rheumatoid arthritis. The diagnostic utility of HMGB1 in Juvenile Idiopathic Arthritis (JIA) is still unclear. The aim was to examine whether serum HMGB1 levels are associated with inflammation, radiological disease progression, and long-term prognosis in JIA. METHODS: We included 131 children with JIA from a population-based prevalence study; 38 of them were prospectively followed up for 10 years. Clinical and laboratory disease characteristics at study entry and after 10 years as well as radiological progression over 10 years were recorded. HMGB1 levels were analyzed by an ELISA. RESULTS: The HMGB1 levels were similar in children with different JIA subgroups and in children with established (53%) or newly diagnosed (47%) disease. HMGB1 levels did not differ between groups at entry into the study or at 10 years, by sex, or by the presence or absence of RF or ANA antibodies. HMGB1 levels at the study entry correlated with HMGB1 levels at 10 years and with blood neutrophil count. Most importantly, children with destructive arthritis at 10 years had a tendency toward higher HMGB1 levels at study entry (median 1.2 vs 0.6ng/ml, ns) and displayed 4-fold higher circulating HMGB1 levels (median 3.4 vs 0.8ng/ml, p = 0.0014) than children without radiological destructions. CONCLUSIONS: Our results suggest that HMGB1 is a marker of inflammatory activity in children with JIA. Higher serum HMGB1 levels are related to more destructive JIA and could be used as a negative prognostic marker at the disease start. TRIAL REGISTRATION: Clinicaltrials.gov NCT01905319. Registered July 16, 2013.
Authors: Anna-Carin Lundell; Malin Erlandsson; Maria Bokarewa; Hille Liivamägi; Karin Uibo; Sirje Tarraste; Tiina Rebane; Tiina Talvik; Chris Pruunsild; Rille Pullerits Journal: J Immunol Res Date: 2018-11-28 Impact factor: 4.818