HMGB1: a possible prognostic marker for long-term outcome in children in juvenile idiopathic arthritis

• Background: High-mobility group protein B1 (HMGB1), a nuclear protein and endogenous danger signal, has recently been implicated as an important pro-inflammatory mediator in adult rheumatoid arthritis (RA). Serum and synovial fluid HMGB1 levels are increased in patients with RA, HMGB1 is aberrantly expressed in inflamed synovial tissues, and treatment modalities blocking or down-regulating HMGB1 expression ameliorate joint inflammation in humans and mice. The role of HMGB1 in juvenile idiopathic arthritis (JIA) has not yet been not studied. To date, it is not known whether HMGB1 could have a predictive prognostic value in children with JIA. Objectives: Our aim was to analyse HMGB1 in patients with JIA and to determine its association with disease activity and long-term prognosis. Methods: Blood samples of 131 Estonian children with JIA (74 girls/56 boys, mean age 9.4±0.4 years, mean disease duration 9.1± 1.7 months) diagnosed according to International League of Associations for Rheumatology (ILAR) criteria were included in population-based incidence/prevalence study. From this study population, 38 patients (22 females/16 males) were recruited to a follow-up visit 10 years later. Clinical disease characteristics, inflammatory and immunological parameters at study start and at 10 years, as well as radiological disease progress at the 10-year follow-up, were recorded. HMGB1 levels at both time points were analysed using ELISA. Results: HMGB1 levels in serum (n = 131) at study start correlated with C-reactive protein (CRP). No association was found between HMGB1 levels and children’s age or disease duration. There were no significant differences in HMGB1 levels between groups regarding gender, antinuclear antibodies (ANA) and rheumatoid factor (RF) positivity, human leucocyte antigen (HLA) phenotype or JIA subtype. Patients (n = 38) recruited to the follow-up visit at 10 years were representative of the initial study population regarding sex and immunological and inflammatory parameters but had shorter disease duration at study start. HMGB1 levels in these patients correlated significantly with inflammatory markers: with CRP at study start and with neutrophil count at the 10-year follow-up. A strong positive correlation was found between HMGB1 levels at start and at 10 years in patients who had detectable skeletal ultrasound and/or X-ray changes. Patients with X-ray-verified changes displayed a fourfold higher median HMGB1 level at 10 years compared to patients without radiological changes. Conclusions: Our results suggest that HMGB1 is a marker of inflammatory activity in children with JIA. Higher serum levels of HMGB1 are related to destructive JIA and could be used as a negative prognostic marker at disease start.

Subject headings

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Reumatologi och inflammation (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Rheumatology and Autoimmunity (hsv//eng)

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Pediatrik (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Pediatrics (hsv//eng)

Keyword

Juvenile idiopathic arthritis

HMGB1

prognosis

joint destruction

Publication and Content Type

ref (subject category)

kon (subject category)