Embed Size (px)
Citation preview
Fenotipi ed endotipi di asma: basi patogenetiche ed implicazioni terapeutiche
Lorenzo [email protected]
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.
Targeting the IL-4/IL-13 pathway in asthma
Allergen-induced FEV1 response
Brodalumab significantly improved plaque psoriasis
Papp K et al NEJM 2012Cosmi L et al J Exp Med 2008
healthy skin psoriatic skin
What biolgics for non-Th2 asthma?
Brodalumab binds human interleukin-17RA and blocks the biologic activity of interleukins 17A, 17F, 17A/F heterodimer, and 17E (interleukin-25)
Iwakura Y et al Immunity 2011
Brodalumab blocks both IL-17A and IL-25
The potential role of blocking IL-17 and IL-25 in asthma
Wang YH et al. Curr Opin Immunol 2008
Biological therapies for asthma
Pelaia R et al. Nat Rev Drug Discov 2012
Grazie per l’attenzione
![BPCO E PRINCIPALI FENOTIPI - AMCPamcp.it/wp-content/uploads/2015/10/ercoli.pdfDAI GRANDI NUMERI Si stima che il 4.5% della popolazione generale sia affetta da BPCO [6] La prevalenza](https://img.pdfslide.tips/doc/110x75/60933b0e168a97466e2ef585/bpco-e-principali-fenotipi-dai-grandi-numeri-si-stima-che-il-45-della-popolazione.jpg)
