Genetic variants in donor PTX3 impair antifungal immunity and predispose to invasive aspergillosis after stem cell transplantation

Event Abstract Back to Event Genetic variants in donor PTX3 impair antifungal immunity and predispose to invasive aspergillosis after stem cell transplantation Cristina Cunha1, Franco Aversa2, Alberto Mantovani3, Luigina Romani1 and Agostinho Carvalho1* 1 University of Perugia, Department of Experimental Medicine and Biochemical Sciences, Italy 2 University of Parma, Department of Clinical and Experimental Medicine, Italy 3 University of Milan, Istituto Clinico Humanitas IRCCS, Italy Invasive aspergillosis is a major complication associated with hematopoietic stem cell transplantation, although individual risk varies considerably. Given the pivotal role of the long pentraxin 3 (PTX3) in antifungal immunity, we investigated the contribution of genetic variation in PTX3 to risk of invasive aspergillosis in a discovery cohort of 229 recipients of allogeneic hematopoietic stem cell transplants and their donors. The analysis was validated in a large multicenter study involving 107 cases of invasive aspergillosis and 223 matched controls. A donor homozygous haplotype (h2/h2) in PTX3 increased risk for invasive aspergillosis in the discovery (adjusted hazard ratio, 3.15; P=0.002) and validation (adjusted odds ratio, 2.78; P=0.03) studies. Functionally, the h2/h2 haplotype led to decreased expression of PTX3 in neutrophils, presumably due to impaired mRNA stability, resulting in defective phagocytosis and clearance of the fungus. PTX3 deficiency was confirmed in bronchoalveolar lavage and lung specimens from transplant recipients with h2/h2 donors. In conclusion, our findings disclose a crucial role of PTX3 to human antifungal immunity and point to PTX3 deficiency as an important risk factor for invasive aspergillosis in stem cell transplant recipients. Acknowledgements This work was supported by the European Society of Clinical Microbiology and Infectious Diseases (ESCMID) Research Grant “Genetic variants of PTX3 and invasive aspergillosis: from risk assessment to mechanistic insights”. Cristina Cunha was supported by the Fundação para a Ciência e Tecnologia, Portugal (contract SFRH/BD/65962/2009). Keywords: Invasive Pulmonary Aspergillosis, Hematopoietic Stem Cell Transplantation, Single nucleotide polymorphisms (SNPs), Pentraxin 3, Neutrophils Conference: 15th International Congress of Immunology (ICI), Milan, Italy, 22 Aug - 27 Aug, 2013. Presentation Type: Abstract Topic: Innate immunity Citation: Cunha C, Aversa F, Mantovani A, Romani L and Carvalho A (2013). Genetic variants in donor PTX3 impair antifungal immunity and predispose to invasive aspergillosis after stem cell transplantation. Front. Immunol. Conference Abstract: 15th International Congress of Immunology (ICI). doi: 10.3389/conf.fimmu.2013.02.01021 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 30 Jun 2013; Published Online: 22 Aug 2013. * Correspondence: Dr. Agostinho Carvalho, University of Perugia, Department of Experimental Medicine and Biochemical Sciences, Perugia, Italy, agostinhocarvalho@med.uminho.pt Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Cristina Cunha Franco Aversa Alberto Mantovani Luigina Romani Agostinho Carvalho Google Cristina Cunha Franco Aversa Alberto Mantovani Luigina Romani Agostinho Carvalho Google Scholar Cristina Cunha Franco Aversa Alberto Mantovani Luigina Romani Agostinho Carvalho PubMed Cristina Cunha Franco Aversa Alberto Mantovani Luigina Romani Agostinho Carvalho Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.