[HTML][HTML] Myeloid related protein induces muscle derived inflammatory mediators in juvenile dermatomyositis
K Nistala, H Varsani, H Wittkowski, T Vogl… - Arthritis research & …, 2013 - Springer
K Nistala, H Varsani, H Wittkowski, T Vogl, P Krol, V Shah, K Mamchaoui, PA Brogan, J Roth…
Arthritis research & therapy, 2013•SpringerIntroduction The aetiopathogenesis of juvenile dermatomyositis (JDM) remains poorly
understood. In particular the contribution of monocytes or macrophages, which are
frequently observed to be an infiltrate within muscle tissue very early in the disease process,
is unknown. We hypothesised that these cells secrete the pro-inflammatory myeloid related
protein (MRP) 8/14 which may then contribute to muscle pathology in JDM. Methods In this
study of 56 JDM patients, serum MRP8/14 levels were compared with clinical measures of …
understood. In particular the contribution of monocytes or macrophages, which are
frequently observed to be an infiltrate within muscle tissue very early in the disease process,
is unknown. We hypothesised that these cells secrete the pro-inflammatory myeloid related
protein (MRP) 8/14 which may then contribute to muscle pathology in JDM. Methods In this
study of 56 JDM patients, serum MRP8/14 levels were compared with clinical measures of …
Introduction
The aetiopathogenesis of juvenile dermatomyositis (JDM) remains poorly understood. In particular the contribution of monocytes or macrophages, which are frequently observed to be an infiltrate within muscle tissue very early in the disease process, is unknown. We hypothesised that these cells secrete the pro-inflammatory myeloid related protein (MRP) 8/14 which may then contribute to muscle pathology in JDM.
Methods
In this study of 56 JDM patients, serum MRP8/14 levels were compared with clinical measures of disease activity. Muscle biopsies taken early in disease were assessed by immunohistochemistry to determine the frequency and identity of MRP-expressing cells. The effects of MRP stimulation and endoplasmic reticulum (ER) stress on muscle were tested in vitro. Serum or supernatant levels of cytokines were analyzed by multiplex immunoassay.
Results
Serum MRP8/14 correlated with physician’s global assessment of disease activity in JDM (R = 0.65, p = 0.0003) and muscle strength/endurance, childhood myositis assessment score (CMAS, R = −0.55, p = 0.004). MRP8/14 was widely expressed by CD68+ macrophages in JDM muscle tissue. When cultured with human myoblasts, MRP8 led to the secretion of MCP-1 and IL-6, which was enhanced by ER stress. Both inflammatory mediators were detected in significantly higher levels in the serum of JDM patients compared to healthy controls.
Conclusions
This study is the first to identify serum MRP8/14 as a potential biomarker for disease activity in JDM. We propose that tissue infiltrating macrophages secreting MRP8/14 may contribute to myositis, by driving the local production of cytokines directly from muscle.
Springer