Background/Purpose: Low-density lipoprotein receptor–related protein 1 (LRP1), a transmembrane protein, mediates endocytosis of an array of extracellular ligands.  LRP1 has intracellular and extracellular domains. With inflammation the extracellular domain can shed into the circulation as soluble LRP1 (sLRP1).  Increased sLRP1 has been reported in adult rheumatoid arthritis but not in childhood arthritis.  This study aimed to determine, in children with juvenile idiopathic arthritis (JIA), levels of sLRP1 and correlations with age, clinical indicators of disease activity, and inflammatory biomarkers.  

Methods: 111 newly diagnosed, treatment naïve children with JIA from 11 Canadian pediatric rheumatology centers were studied.  Plasma was assayed for sLRP1 by ELISA and for 47 inflammation-related biomarkers by bead-based, multiplex immunoassays.  Pearson correlations identified relationships between sLRP1 levels and indicators of disease activity and logarithmic transformed multiplex biomarker levels.  Differences in mean sLRP1 levels in relation to presence/absence of morning stiffness were analyzed by t-tests.  Comparison of sLRP1 means across JIA categories was assessed by ANOVA.    

Results:  Mean sLRP1 levels were highest in rheumatoid factor negative (RF-) polyarticular, oligoarticular, and psoriatic JIA and lowest in systemic JIA (Table). 

ANOVA did not show significant mean sLRP1 differences among JIA subtypes.  Groups of children stratified as < age 4 years and < age 5 years had higher levels of sLRP1 than older children (p=0.019 and 0.028 respectively). sLRP1 levels did not correlate with active joint count, presence of morning stiffness, ESR, or CRP. In oligoarticular and RF- polyarticular JIA levels of sLRP1 were positively correlated with the same 32 biomarkers encompassing a wide array of pro- and anti-inflammatory cytokines, chemokines,  matrix metalloproteinases, and growth factors (p=0.026 to <0.001).  An additional 2 correlations with biomarkers were found in RF- polyarticular JIA. In contrast, sLRP1 levels correlated with only a small number of the 47  biomarkers in other JIA subtypes (9 in psoriatic ,  4 in RF+ polyarticular, 2 in enthesitis related arthritis, and none in systemic).

Conclusion:  In this first report of sLRP1 in JIA we found correlations of sLRP1 with young age and, in oligoarticular and RF-  polyarticular subtypes, with inflammation-related biomarkers. Findings suggest that oligoarticular and RF- polyarticular JIA are linked pathobiologically with respect to sLRP1 and the profile of biomarkers with which it is associated. Plasma sLRP1 could be a valuable biomarker reflective of inflammatory-mediated processes related to JIA subtype and onset age.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/soluble-low-density-lipoprotein-receptor-related-protein-1-in-juvenile-idiopathic-arthritis/