Increased Levels of Eotaxin and MCP-1 in Juvenile Dermatomyositis Median 16.8 Years after Disease Onset; Associations with Disease Activity, Duration and Organ Damage

Abstract

ObjectiveTo compare cytokine profiles in patients with juvenile dermatomyositis (JDM) after medium to long-term follow-up with matched controls, and to examine associations between cytokine levels and disease activity, disease duration and organ damage.MethodsFifty-four JDM patients were examined median 16.8 years (2–38) after disease onset (follow-up) and compared with 54 sex- and age-matched controls. Cytokine concentrations in serum were quantified by Luminex technology. In patients, disease activity score (DAS), myositis damage index (MDI) and other disease parameters were collected by chart review (early parameters) and clinical examination (follow-up).ResultsSerum levels of eotaxin, monocyte chemoattractant protein-1 (MCP-1) and interferon-inducible protein 10 (IP-10) were elevated in JDM patients compared to controls (31.5%, 37.2% and 43.2% respectively, all p<0.05). Patients with active (n = 28), but not inactive disease (n = 26) had a higher level of MCP-1 than their respective controls. Levels of eotaxin and MCP-1 correlated with disease duration (r = 0.47 and r = 0.64, both p<0.001) and age in patients, but not with age in controls. At follow-up, MDI was associated with MCP-1(standardized β = 0.43, p = 0.002) after adjusting for disease duration and gender. High MDI 1 year post-diagnosis predicted high levels of eotaxin and MCP-1 at follow-up (standardized β = 0.24 and 0.29, both p<0.05) after adjusting for disease duration and gender.ConclusionPatients with JDM had higher eotaxin, MCP-1 and IP-10 than controls. High eotaxin and MCP-1 at follow-up was predicted by early disease parameters, and MCP-1 was associated with organ damage at follow-up, highlighting a role of these chemokines in JDM.

Galectin‐9 and CXCL10 as Biomarkers for Disease Activity in Juvenile Dermatomyositis: A Longitudinal Cohort Study and Multicohort Validation

“…A recent study using the SOMAscan assay also identified both galectin-9 and CXCL10 among the top up-regulated proteins in juvenile DM, correlating with disease activity as assessed by the PhGA (53). CXCL10 levels were previously shown to correlate with disease activity in juvenile DM (26,(30)(31)(32)54), and CXCL10 is well known to be an interferon-inducible chemokine that can be elevated in other types of myositis and autoimmune diseases (29,33). In our study, galectin-9 was a specific biomarker for inflammatory myopathies.…”

Submaximal Exercise Capacity in Juvenile Dermatomyositis after Longterm Disease: The Contribution of Muscle, Lung, and Heart Involvement

“…MRI detected muscle damage (such as muscle atrophy and fatty infiltration) was found in approximately 50% of patients. The serum cytokine eotaxin and the serum myokines MCP-1 and IP-10 were elevated in patients compared to controls (77). MCP-1 was also elevated in patients with active disease compared to respective controls, and correlated with disease damage in the whole patient group.…”

Dysregulated NK cell PLCγ2 signaling and activity in juvenile dermatomyositis

“…The innate immune system also appears to play a role in JDM. Plasmacytoid dendritic cells and macrophage-secreted proteins are present in inflamed JDM patient muscles (12,13), and chemokines eotaxin, monocyte chemoattractant protein-1, and IFN-γ-induced protein 10 are elevated in JDM patient serum in comparison with healthy controls (14). In addition, specific TNF and IL-1 alleles as well as a type I IFN-stimulated gene signature are associated with JDM disease risk (15,16).…”