Anti-IL21 Monoclonal antibody, clone 4B4-O3 [eFluor® 660]

A recent study in the nonobese diabetic (NOD) mouse demonstrated the involvement of interleukin (IL)-21 in the pathogenesis of type 1 diabetes. A strong susceptibility locus, Idd3, has also been mapped to the interval containing the routine gene for IL-21 (I/21), making I/21 and the human orthologue IL21 a functional and positional candidate gene for type 1 diabetes. To investigate the contribution of the human genes for IL-21 and its receptor (IL-21R) to susceptibility to type 1 diabetes, we re-sequenced IL21 to identify novel sequence variants, searched for informative variants of IL21R, and studied the association of theme variants with the disease. Two polymorphisms, a single nucleotide polymorphism (SNP) and a mononucleotide repeat polymorphism, were identified for IL21, and an allele of the mononucleotide repeat polymorphism was positively associated with the IL21R were identified, one of which was associated with the disease. Scoring of individuals according to the status of these alleles showed a significant trend for high scores for susceptibility in diabetes patients, suggesting the contribution of IL21 and IL21R to disease susceptibility in an additive manner. These data suggest a contribution of IL21 and IL21R to genetic susceptibility to type 1 diabetes and possible involvement of IL-21 and its receptor system in the disease pathogenesis.

Background: T helper (Th) 17 cells may play a role in allergic asthma. This study assessed the effect of allergen inhalation challenge on circulating Th17 cells and related cytokines in allergic asthmatics. Methods: Peripheral blood mononuclear cells were collected from 16 atopic asthmatics before and 24 h after allergen challenge, as well as from 10 atopic nonasthmatics and 10 normal controls. Cells were stained for Th17 cytokines and their receptors (IL-17A, IL-17F, IL-21, IL22, IL-17R, and IL-23R) using flow cytometry. Cytokine concentrations from cell culture supernatants were quantified using a multiplex assay for IL-17A, IL-17F, IL-21, IL-22, and IL-23. Results: At baseline, asthmatics had a higher percentage of circulating Th17 cells (1.2 +/- 0.5%) compared to normal controls (0.9 +/- 0.66%, p < 0.001) but not compared to atopic nonasthmatics (1.13 +/- 0.5%). There was a significant increase in Th17 cells in asthmatics after allergen challenge to 1.55 +/- 0.4% (p < 0.05) and a trend toward significance in IL-17R expression from 3.4 +/- 4.3 to 6.86 +/- 6.84% after allergen challenge (p = 0.06). There was also a significant reduction in IL21- positive cells following allergen challenge from 3.46 +/- 1.85 to 2.33 +/- 1.37% (p < 0.001). There were no significant differences in IL-17F, IL-22 and IL-23R expression. The concentration of IL-17A in culture supernatant was significantly higher in asthmatics compared to normal controls and IL-7A significantly increased 24 h after allergen challenge. Conclusions: The increase of Th17 cells and IL-17A in atopic asthma after allergen inhalation challenge suggests a possible role for Th17 in allergen-induced airway responses. (C) 2014 S. Karger AG, Basel