Fenotipi ed endotipi di asma: basi patogenetiche ed implicazioni terapeutiche Lorenzo Cosmi [email protected]XXIX Congresso Sezione SIAIC Toscana VIII Congresso Sezione SIAIC Toscana-Emilia Romagna-San Marino I Congresso della Sezione della Società Italiana Allergologia ed Immunologia Clinica Umbria e Marche Firenze, 12-13 aprile 2013
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Fenotipi ed endotipi di asma: basi patogenetiche ed implicazioni terapeutiche
XXIX Congresso Sezione SIAIC ToscanaVIII Congresso Sezione SIAIC Toscana-Emilia Romagna-San MarinoI Congresso della Sezione della Società Italiana Allergologia ed
Immunologia Clinica Umbria e MarcheFirenze, 12-13 aprile 2013
Young Kim H et al. Nat. Immunol. 2010
Asma phenotypes and pathophysiological mechanisms
Wenzel SE Nat Med 2012
Th2 lymphocytes in asthma pathogenesis
Romagnani S. JACI 2000
Lambrecht BN et al. Nat Med 2012
The epithelial/ILC network in allergic sensitization
Walker JA et al. Curr Opin Immunol 2013
IL-4-, but not IFN-γγγγ-,,,, producing T cells in the bronchi of allergen-challenged asthmatics
Panina-Bordignon P et al. JCI 2001Holgate ST Nat Med 2012
Non-Th2 asthma: possible role of Th17 lymphocytes
Wenzel SE Nat Med 2012
Human effector CD4+ T cells
Cosmi L et al. Allergy 2011
Th17/Th2 Der p1 specific lymphocytes in asthmatic allergic patients
Cosmi L et al. JACI 2010
RORCGATA-3CCR6
CD161 IL-4R
IL-4
Th17/Th2Th17
RORCT-betCCR6
CD161 IL-4R
Wang YH et al. Curr Allergy Asthma Rep 2011
Th2 lymphocytes can shift to Th2 in response to IL-1 and IL-6, and IL-21
Th2 and Th17 lymphocytes support distinct asthma phenotypes
Cosmi L et al. Allergy 2011
Developing targeted biologic therapies in asthma
Pelaia R et al. Nat Rev Drug Discov 2012
Fanta CH NEJM 2009
Omalizumab in IgE-mediated asthma
Nair P et al. NEJM 2009
Mepolizumab is efficacy in prednisone-dependent asthma with eosinophilia
Pavord ID et al. Lancet 2012
The role of reslizumab in eosinophilic asthma
Castro M ey t al. Am J Respir Crit Care Med 2011
Patients with eosinophilic asthma that is poorly controlled with high-dose inhaled corticosteroid, were randomly assigned to receive infusions of reslizumab (53) or placebo (53)
Molfino NA et al. Clin Exp All 2011
Ingram J et al. JACI 2012
IL-13 in Th2 allergic asthma
Corren J et al. NEJM. 2011
Lebrikizumab treatment in adults with asthma
Patients with uncontrolled asthma despite treatment with medium-dose to high-dose inhaled glucocorticoids, were treated with lebrikizumab, an IgG4 humanized monoclonal antibody that specifically binds to interleukin-13 and inhibits its function
IL-4/IL-13 receptors and signaling pathways
Ingram J et al. JACI 2012
Wenzel S et al. Lancet 2007
Pitrakinra is a recombinant human IL-4 variant that inhibits the binding of interleukin 4 and interleukin 13 to interleukin-4Ralpha receptor complexes.In study 2, in the pitrakinra group, there was a significative lower decrease in FEV1 in response to allergen challlenge than in the placebo group.