Complement lectin pathway protein levels reflect disease activity in juvenile idiopathic arthritis: a longitudinal study of the Nordic JIA cohort

Mia Glerup,For The Nordic Study Group Of Pediatric Rheumatology (Nosper) ,Steffen Thiel,Kristiina Aalto,Ellen Nordal,Troels Herlin,Lillemor Berntson,Susan Nielsen,Veronika Rypdal,Maria Ekelund,Ellen Dalen Arnstad,Marite Rygg,Anders Fasth,Suvi Peltoniemi

doi:10.1186/s12969-019-0367-9

Abstract

BackgroundTo determine the serum levels of the lectin pathway proteins early in the disease course and 17 years after disease onset and to correlate the protein levels to markers of disease activity in participants from a population-based Nordic juvenile idiopathic arthritis (JIA) cohort. Additionally, to assess the predictive value of lectin pathway proteins with respect to remission status.MethodsA population-based cohort study of consecutive cases of JIA with a disease onset from 1997 to 2000 from defined geographical areas of Finland, Sweden, Norway and Denmark with 17 years of follow-up was performed. Clinical characteristics were registered and H-ficolin, M-ficolin, MASP-1, MASP-3, MBL and CL-K1 levels in serum were analyzed.ResultsIn total, 293 patients with JIA were included (mean age 23.7 ± 4.4 years; mean follow-up 17.2 ± 1.7 years). Concentrations of the lectin protein levels in serum were higher at baseline compared to the levels 17 years after disease onset (p ≤ 0.006, n = 164). At baseline, the highest level of M-ficolin was observed in systemic JIA. Further, high M-ficolin levels at baseline and at 17-year follow-up were correlated to high levels of ESR. In contrast, high MASP-1 and MASP-3 tended to correlate to low ESR. CL-K1 showed a negative correlation to JADAS71 at baseline.None of the protein levels had prognostic abilities for remission status 17 years after disease onset.ConclusionWe hypothesize that increased serum M-ficolin levels are associated with higher disease activity in JIA and further, the results indicate that MASP-1, MASP-3 and CL-K1 are markers of inflammation.

Highlights

To determine the serum levels of the lectin pathway proteins early in the disease course and 17 years after disease onset and to correlate the protein levels to markers of disease activity in participants from a populationbased Nordic juvenile idiopathic arthritis (JIA) cohort
We found that a high M-ficolin level at baseline and 17-year follow-up was correlated to high Erythrocyte sedimentation rate (ESR) and high mannose-binding lectin (MBL)-associated serine proteases (MASP)-1 and MASP-3 tended to correlate to low ESR
We found a tendency that high MASP-1 and MASP-3 were associated with low disease activity and Collektin Kidney 1 (CL-K1) was negatively correlated to JADAS71 at baseline

Summary

Introduction

To determine the serum levels of the lectin pathway proteins early in the disease course and 17 years after disease onset and to correlate the protein levels to markers of disease activity in participants from a populationbased Nordic juvenile idiopathic arthritis (JIA) cohort. Juvenile idiopathic arthritis (JIA), which is the most common rheumatic disease in childhood [1, 2], is a heterogeneous disease. Upon the binding to adequate patterns enzymatic proteins called MBL-associated serine proteases (MASPs) become activated [15,16,17]. The active protease of MASP-2 cleaves C4 and C2 forming a C4b2a convertase that subsequently cleaves C3. Active forms of MASP-3 activates Factor D which is a key enzyme of the alternative pathway in the complement system [18]

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