Evidence for M2 macrophage activation in patients with enthesitis-related arthritis category of juvenile idiopathic arthritis

Recently, an increase in CD163⁺ macrophages in ileal biopsies from ankylosing spondylitis patients and an increase in intermediate monocytes in enthesitis-related arthritis (ERA) have been reported. Thus, we studied sCD163 levels as M2 macrophage marker in serum and synovial fluid (SF) of ERA children and CD163 expression on monocyte subsets. Serum samples from ERA patients and healthy controls (HC) were assayed for sCD163 (ELISA). Serum and SF from ERA patients were analyzed when available from same patient (paired samples). In 10 patients, the CD163 expression level was analyzed on monocyte subsets by flow cytometry. Results are expressed as median (interquartile range (IQR)). Sera from 85 patients, SF from 32 ERA patients, and serum from 46 HC were analyzed. The average age at inclusion was 16 ± 3.24 years and age at onset was 11.2 ± 2.79 years. Seventy-nine of them were boys and HLA-B27 was positive in 64/80 patients. The median serum sCD163 levels were higher in patients [1080 (1305.2) ng/ml] than HC [780 (812.5) ng/ml; p < 0.001]. The SF levels [9000 (1250) ng/ml] were much higher than serum [3800 (3287.66) ng/ml; p < 0.001]. Disease activity data was available in 56 patients. Mean tender joint count was 2 (3), swollen joint count was 2 (2), ESR was 70 (65) mm and CRP was 7.1 (8.9) mg/dl. Serum sCD163 levels correlated with SF but not with disease activity. Intermediate monocytes (CD14⁺CD16⁺) from ERA patients had higher CD163 expression than HC. Elevated sCD163 levels in ERA patient’s sera and even higher levels in paired SF suggest towards activation of alternatively activated macrophages in ERA. Lack of correlation with activity may suggest that they have an immune-regulatory role in ERA.