title: Aberrant expression of regulatory cytokine IL-35 and pattern recognition receptor NOD2 in patients with allergic asthma.
abstract: We investigated the plasma concentration of the novel regulatory cytokine IL-35 and intracytosolic pattern recognition receptors nucleotide-binding oligomerization domain (NOD)-like receptors in granulocytes and explored their potential implication in disease severity monitoring of allergic asthma. The expression of circulating IL-35 and other pro-inflammatory mediators in asthmatic patients or control subjects were evaluated using enzyme-linked immunosorbent assay (ELISA). The intracellular expressions of NOD1 and NOD2 in CCR3+ granulocytes were assessed using flow cytometry. Plasma concentrations of IL-35, IL-17A, basophil activation marker basogranulin, and eosinophilic airway inflammation biomarker periostin were significantly elevated in allergic asthmatic patients compared to non-atopic control subjects (all probability (p) <0.05). Both granulocyte markers exhibited significant and positive correlation with plasma IL-35 concentration in asthmatic patients (all p < 0.05). Significant positive correlation was also identified between plasma concentrations of IL-35 and periostin with disease severity score in asthmatic patients (both p < 0.05). The basophil activation allergenicity test was positive in allergic asthmatic patients but not in control subjects. Despite significantly elevated eosinophil count in allergic asthmatic patients, downregulation of NOD2 in CCR3+ granulocytes was observed in these patients (both p < 0.05). A negative correlation between plasma concentrations of tumor necrosis factor family member LIGHT and soluble herpesvirus entry mediator was observed in patients with elevated plasma concentration of IL-35 (p < 0.05). Aberrant expression of NOD2 in granulocytes may be contributed to the impaired innate immunity predisposing allergic asthma. IL-35 may serve as a potential surrogate biomarker for disease severity of allergic asthma.
authors.affiliation: Department of Chemical Pathology, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, NT, Hong Kong, ck-wong@cuhk.edu.hk.
authors.forename: Chun Kwok
authors.initials: CK
authors.lastname: Wong
authors.forename: Ting Fan
authors.initials: TF
authors.lastname: Leung
authors.forename: Ida Miu Ting
authors.initials: IM
authors.lastname: Chu
authors.forename: Jie
authors.initials: J
authors.lastname: Dong
authors.forename: Yvonne Yi On
authors.initials: YY
authors.lastname: Lam
authors.forename: Christopher Wai Kei
authors.initials: CW
authors.lastname: Lam
mesh_terms: D000293:Adolescent; D000328:Adult; D001249:Asthma / Q000175:diagnosis / Q000378:metabolism*; D015415:Biomarkers / Q000378:metabolism; D016207:Cytokines / Q000096:biosynthesis; D005260:Female; D005786:Gene Expression Regulation; D006098:Granulocytes / Q000378:metabolism; D006801:Humans; D006967:Hypersensitivity / Q000175:diagnosis / Q000378:metabolism*; D007113:Immunity, Innate / Q000502:physiology; D007378:Interleukins / Q000096:biosynthesis*; D008297:Male; D053473:Nod2 Signaling Adaptor Protein / Q000096:biosynthesis*; D055815:Young Adult
chemical_list: D015415:Biomarkers; D016207:Cytokines; D007378:Interleukins; C429018:NOD2 protein, human; D053473:Nod2 Signaling Adaptor Protein; C532417:interleukin-35, human