Abstract
BackgroundNeutrophils are the most prevalent immune cells in the synovial fluid in inflamed joints of children with oligoarticular juvenile idiopathic arthritis (JIA). Despite this, little is known about neutrophil function at the site of inflammation in JIA and how local neutrophils contribute to disease pathogenesis. This study aimed to characterize the phenotype and function of synovial fluid neutrophils in oligoarticular JIA.MethodsNeutrophils obtained from paired blood and synovial fluid from patients with active oligoarticular JIA were investigated phenotypically (n = 17) and functionally (phagocytosis and oxidative burst, n = 13) by flow cytometry. In a subset of patients (n = 6), blood samples were also obtained during inactive disease at a follow-up visit. The presence of CD206-expressing neutrophils was investigated in synovial biopsies from four patients by immunofluorescence.ResultsNeutrophils in synovial fluid had an activated phenotype, characterized by increased CD66b and CD11b levels, and most neutrophils had a CD16hi CD62Llowaged phenotype. A large proportion of the synovial fluid neutrophils expressed CD206, a mannose receptor not commonly expressed by neutrophils but by monocytes, macrophages, and dendritic cells. CD206-expressing neutrophils were also found in synovial tissue biopsies. The synovial fluid neutrophil phenotype was not dependent on transmigration alone. Functionally, synovial fluid neutrophils had reduced phagocytic capacity and a trend towards impaired oxidative burst compared to blood neutrophils. In addition, the effector functions of the synovial fluid neutrophils correlated negatively with the proportion of CD206+ neutrophils.ConclusionsNeutrophils in the inflamed joint in oligoarticular JIA were altered, both regarding phenotype and function. Neutrophils in the synovial fluid were activated, had an aged phenotype, had gained monocyte-like features, and had impaired phagocytic capacity. The impairment in phagocytosis and oxidative burst was associated with the phenotype shift. We speculate that these neutrophil alterations might play a role in the sustained joint inflammation seen in JIA.
Highlights
Neutrophils are the most prevalent immune cells in the synovial fluid in inflamed joints of children with oligoarticular juvenile idiopathic arthritis (JIA)
S100A8/A9, a protein released from activated neutrophils, was only present on the surface of less than 3% of both synovial fluid and blood neutrophils (Fig. 1h)
As the reduced capacity of phagocytosis and oxidative burst was associated with the phenotype shift of synovial neutrophils towards a monocyte-like pattern with increased surface expression of CD206, we speculate that alterations in phenotype and function could be connected
Summary
Neutrophils are the most prevalent immune cells in the synovial fluid in inflamed joints of children with oligoarticular juvenile idiopathic arthritis (JIA). This study aimed to characterize the phenotype and function of synovial fluid neutrophils in oligoarticular JIA. Juvenile idiopathic arthritis (JIA) is an inflammatory rheumatic joint disease affecting children. The most common subtype in the Western world is oligoarticular JIA [4], commonly characterized by asymmetric disease onset with inflammation in one to four large joints [3, 5]. The importance of the innate immune response is reflected in the treatment of oligoarticular JIA, where the most commonly used drugs are either nonspecific or target important components of the innate immune system such as tumor necrosis factor alpha (TNFα) and interleukin 6 (IL-6), while therapies targeting T and B cells in the adaptive immune system are more seldom used [10, 11]
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