Dataset Information

Novel SNPs in IL-17F and IL-17A genes associated with somatic cell count in Chinese Holstein and Inner-Mongolia Sanhe cattle.

ABSTRACT: Bovine mastitis is the most common and costly disease of lactating cattle worldwide. Apart from milk somatic cell count (SCC) and somatic cell score (SCS), serum cytokines such as interleukin-17 (IL-17) and interleukin-4 (IL-4) may also be potential indicators for bovine mastitis. The present study was designed to investigate the effects of single nucleotide polymorphisms (SNPs) in bovine IL-17F and IL-17A genes on SCC, SCS and serum cytokines in Chinese Holstein and Inner-Mongolia Sanhe cattle, and to compare the mRNA expression variations of the cows with different genotypes.A total of 464 lactating cows (337 Holstein and 127 Inner-Mongolia Sanhe cattle) were screened for SNPs identification and the data were analyzed using fixed effects of herd, parity, season and year of calving by general linear model procedure. The results revealed that SNP g.24392436C?>?T in IL-17F and SNP g.24345410A?>?G in IL-17A showed significant effects on SCC and IL-4 in Holstein (n?=?337) and on IL-17 and IL-4 in Sanhe cattle (n?=?127). The homozygous GG genotype of SNP g.24345410A?>?G had significantly higher mRNA expression compared with the heterozygous AG genotype.The results indicate that IL-17F and IL-17A could be powerful candidate genes of mastitis resistance and the significant SNPs might be useful genetic markers against mastitis in both dairy and dual purpose cattle.

SUBMITTER: Usman T

PROVIDER: S-EPMC5237346 | biostudies-other | 2017

REPOSITORIES: biostudies-other

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Novel SNPs in IL-17F and IL-17A genes associated with somatic cell count in Chinese Holstein and Inner-Mongolia Sanhe cattle.

Usman Tahir T Wang Yachun Y Liu Chao C He Yanghua Y Wang Xiao X Dong Yichun Y Wu Hongjun H Liu Airong A Yu Ying Y

Journal of animal science and biotechnology 20170113

<h4>Background</h4>Bovine mastitis is the most common and costly disease of lactating cattle worldwide. Apart from milk somatic cell count (SCC) and somatic cell score (SCS), serum cytokines such as interleukin-17 (IL-17) and interleukin-4 (IL-4) may also be potential indicators for bovine mastitis. The present study was designed to investigate the effects of single nucleotide polymorphisms (SNPs) in bovine IL-17F and IL-17A genes on SCC, SCS and serum cytokines in Ch ...[more]

PMID: 28101335

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Project description:Interleukin (IL)-17A is a key driver of inflammation and the principal target of anti-IL-17 therapeutic monoclonal antibodies. IL-17A, and its structurally similar family member IL-17F, have been shown to be functionally dysregulated in certain human immune-mediated inflammatory diseases such as psoriasis, psoriatic arthritis, and axial spondyloarthritis. Given the overlapping biology of these two cytokines, we postulated that dual neutralization of IL-17A and IL-17F may provide a greater depth of clinical response in IL-17-mediated diseases than IL-17A inhibition alone. We identified 496.g1, a humanized antibody with strong affinity for IL-17A but poor affinity for IL-17F. Affinity maturation of 496.g1 to 496.g3 greatly enhanced the affinity of the Fab fragment for IL-17F while retaining strong binding to IL-17A. As an IgG1, the affinity for IL-17A and IL-17F was 3.2 pM and 23 pM, respectively. Comparison of 496.g3 IgG1 with the commercially available anti-IL-17A monoclonal antibodies ixekizumab and secukinumab, by surface plasmon resonance and in a human in vitro IL-17A functional assay, showed that 496.g3 and ixekizumab display equivalent affinity for IL-17A, and that both antibodies are markedly more potent than secukinumab. In contrast to ixekizumab and secukinumab, 496.g3 exhibited the unique feature of also being able to neutralize the biological activity of IL-17F. Therefore, antibody 496.g3 was selected for clinical development for its ability to neutralize the biologic function of both IL-17A and IL-17F and was renamed bimekizumab (formerly UCB4940). Early clinical data in patients with psoriasis, in those with psoriatic arthritis, and from the Phase 2 studies in psoriasis, psoriatic arthritis, and ankylosing spondylitis, are encouraging and support the targeted approach of dual neutralization of IL-17A and IL-17F. Taken together, these findings provide the rationale for the continued clinical evaluation of bimekizumab in patients with immune-mediated inflammatory diseases.

Dataset Information

Novel SNPs in IL-17F and IL-17A genes associated with somatic cell count in Chinese Holstein and Inner-Mongolia Sanhe cattle.

Publications

Novel SNPs in <i>IL-17F</i> and <i>IL-17A</i> genes associated with somatic cell count in Chinese Holstein and Inner-Mongolia Sanhe cattle.

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