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10.1016/j.jaci.2016.08.032

http://scihub22266oqcxt.onion/10.1016/j.jaci.2016.08.032
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C5376378!5376378!27702673
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suck abstract from ncbi


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pmid27702673      J+Allergy+Clin+Immunol 2017 ; 139 (5): 1548-1558.e4
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  • Mechanism of Th2/Th17-predominant and Neutrophilic, Th2/Th17-low Subtypes of Asthma #MMPMID27702673
  • Liu W; Liu S; Verma M; Zafar I; Good JT; Rollins D; Groshong S; Gorska MM; Martin RJ; Alam R
  • J Allergy Clin Immunol 2017[May]; 139 (5): 1548-1558.e4 PMID27702673show ga
  • Background: The mechanism of Th2/Th17-predominant and Th2/Th17-low asthma is unknown. Objective: To study the immune mechanism of Th2/Th17-predominant and Th2/Th17-low asthma. Methods: In a previously reported cohort of 60 asthmatic patients, 16 patients were immunophenotyped with Th2/Th17-predominant asthma and 22 patients with Th2/Th17-low asthma. We examined BAL leukocytes, cytokines, mediators, and epithelial cell function for these asthma subgroups. Results: Th2/Th17-predominant asthma had elevated IL1?, IL6, IL23, C3a and serum amyloid A (SAA) in BAL, and correlated with IL1? and C3a. Th2/Th17 cells expressed higher levels of the IL1 receptor and p-p38 MAPK. Anakinra, an IL1 receptor antagonist protein, inhibited BAL Th2/Th17 cells. Th2/Th17-low asthma had two distinct subgroups?neutrophilic asthma (45%) and pauci-inflammatory asthma (55%). This contrasted with Th2/Th17-predominant and Th2-predominant asthma, which had neutrophilic asthma in 6% and 0% of patients, respectively. BAL neutrophils strongly correlated with BAL myeloperoxidase, IL8, IL1?, IL6, G-CSF, and GM-CSF.. Sixty percent of the patients with neutrophilic asthma had a pathogenic microorganism in BAL culture, which suggested a subclinical infection. Conclusion: We uncovered a critical role for the IL1? pathway in Th2/Th17-predminant asthma. A subgroup of Th2/Th17-low patients had neutrophilic asthma and elevated BAL IL1?, IL6, IL8, G-CSF, and GM-CSF. IL1? was directly involved in IL8 production and likely contributed to neutrophilic asthma. Sixty percent of neutrophilic patients had a subclinical infection.
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