title: Intermediate monocytes are increased in enthesitis-related arthritis, a category of juvenile idiopathic arthritis.
abstract: Microarray of peripheral blood (PB) and synovial fluid mononuclear cells (PBMC, SFMC) of patients with juvenile idiopathic arthritis-enthesitis-related arthritis (JIA-ERA) has shown the involvement of monocytes. On the basis of CD14 and CD16 expression, monocytes are classified as classical, intermediate and non-classical. In response to Toll-like receptor (TLR) stimulation, intermediate monocytes produce proinflammatory cytokines and play a role in inflammatory diseases. Therefore, we have studied the microarray profile of monocytes, the frequency of their subsets and cytokine production. Monocyte-specific microarray analysis was performed in six healthy controls' PBMC and six patients' PBMC and SFMC using Illumina chips WG12. Monocyte subsets were assessed in 46 patients with JIA-ERA and 17 healthy controls and 17 disease controls by flow cytometry. Interleukin (IL)-23 and tumour necrosis factor (TNF) levels were measured in culture supernatants of eight controls and seven patients' PBMC/SFMC with/without lipopolysaccharide (LPS) stimulation. Cytokine-producing intermediate monocytes were assessed by flow cytometry. Genes related to antigen presentation, cytokine signalling and TLR pathway were regulated differentially in PB and synovial monocytes of patients with JIA-ERA. Key genes of intermediate monocytes, such as CLEC10A and MARCO, were expressed three- to fourfold more in JIA-ERA. In PB, the frequency of intermediate monocytes was significantly higher in JIA-ERA (4·90% ± 3·5) compared to controls (1·8% ± 1·06; P < 0·001). Patients' synovial cells also had more intermediate monocytes compared to PB (11·25% ± 11·32, 5·9% ± 4·8; P = 0.004). Intermediate monocytes are the major producers of IL-23. Thus, intermediate monocytes may play an important role in JIA-ERA, possibly by producing cytokines, and contribute to joint inflammation.
authors.affiliation: Department of Clinical Immunology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India.
authors.forename: P
authors.initials: P
authors.lastname: Gaur
authors.affiliation: Department of Clinical Immunology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India.
authors.forename: A
authors.initials: A
authors.lastname: Myles
authors.affiliation: Department of Clinical Immunology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India.
authors.forename: R
authors.initials: R
authors.lastname: Misra
authors.affiliation: Department of Clinical Immunology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India.
authors.forename: A
authors.initials: A
authors.lastname: Aggarwal
mesh_terms: D000293:Adolescent; D000328:Adult; D001171:Arthritis, Juvenile / Q000276:immunology*; D002454:Cell Differentiation; D002478:Cells, Cultured; D002648:Child; D005260:Female; D006801:Humans; D053759:Interleukin-23 / Q000378:metabolism; D037181:Lectins, C-Type / Q000235:genetics*; D018950:Lipopolysaccharide Receptors / Q000378:metabolism; D008070:Lipopolysaccharides / Q000276:immunology; D008297:Male; D009000:Monocytes / Q000502:physiology*; D017452:Receptors, IgG / Q000378:metabolism; D011971:Receptors, Immunologic / Q000235:genetics*; D013583:Synovial Membrane / Q000276:immunology*; D046888:Tissue Array Analysis; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D055815:Young Adult
chemical_list: C545222:CLEC10A protein, human; D053759:Interleukin-23; D037181:Lectins, C-Type; D018950:Lipopolysaccharide Receptors; D008070:Lipopolysaccharides; C490460:MARCO protein, human; D017452:Receptors, IgG; D011971:Receptors, Immunologic; D014409:Tumor Necrosis Factor-alpha
keywords: gene expression; inflammation; intermediate monocytes; juvenile arthritis; synovial fluid