Abstract
BACKGROUND: The soluble pattern-recognition receptor known as long pentraxin 3 (PTX3) has a nonredundant role in antifungal immunity. The contribution of single-nucleotide polymorphisms (SNPs) in PTX3 to the development of invasive aspergillosis is unknown. METHODS: We screened an initial cohort of 268 patients undergoing hematopoietic stem-cell transplantation (HSCT) and their donors for PTX3 SNPs modifying the risk of invasive aspergillosis. The analysis was also performed in a multicenter study involving 107 patients with invasive aspergillosis and 223 matched controls. The functional consequences of PTX3 SNPs were investigated in vitro and in lung specimens from transplant recipients. RESULTS: Receipt of a transplant from a donor with a homozygous haplotype (h2/h2) in PTX3 was associated with an increased risk of infection, in both the discovery study (cumulative incidence, 37% vs. 15%; adjusted hazard ratio, 3.08; P = 0.003) and the confirmation study (adjusted odds ratio, 2.78; P = 0.03), as well as with defective expression of PTX3. Functionally, PTX3 deficiency in h2/h2 neutrophils, presumably due to messenger RNA instability, led to impaired phagocytosis and clearance of the fungus. CONCLUSIONS: Genetic deficiency of PTX3 affects the antifungal capacity of neutrophils and may contribute to the risk of invasive aspergillosis in patients treated with HSCT.
| Original language | English |
|---|---|
| Pages (from-to) | 421-432 |
| Number of pages | 12 |
| Journal | New England Journal of Medicine |
| Volume | 370 |
| Issue number | 5 |
| DOIs | |
| Publication status | Published - 2014 |
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ASJC Scopus subject areas
- Medicine(all)
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Genetic PTX3 deficiency and aspergillosis in stem-cell transplantation. / Cunha, Cristina; Aversa, Franco; Lacerda, João F.; Busca, Alessandro; Kurzai, Oliver; Grube, Matthias; Löffler, Jürgen; Maertens, Johan A.; Bell, Alain S.; Inforzato, Antonio; Barbati, Elisa; Almeida, Bruno; Santos E Sousa, Pedro; Barbui, Anna; Potenza, Leonardo; Caira, Morena; Rodrigues, Fernando; Salvatori, Giovanni; Pagano, Livio; Luppi, Mario; Mantovani, Alberto; Velardi, Andrea; Romani, Luigina; Carvalho, Agostinho.
In: New England Journal of Medicine, Vol. 370, No. 5, 2014, p. 421-432.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Genetic PTX3 deficiency and aspergillosis in stem-cell transplantation
AU - Cunha, Cristina
AU - Aversa, Franco
AU - Lacerda, João F.
AU - Busca, Alessandro
AU - Kurzai, Oliver
AU - Grube, Matthias
AU - Löffler, Jürgen
AU - Maertens, Johan A.
AU - Bell, Alain S.
AU - Inforzato, Antonio
AU - Barbati, Elisa
AU - Almeida, Bruno
AU - Santos E Sousa, Pedro
AU - Barbui, Anna
AU - Potenza, Leonardo
AU - Caira, Morena
AU - Rodrigues, Fernando
AU - Salvatori, Giovanni
AU - Pagano, Livio
AU - Luppi, Mario
AU - Mantovani, Alberto
AU - Velardi, Andrea
AU - Romani, Luigina
AU - Carvalho, Agostinho
PY - 2014
Y1 - 2014
N2 - BACKGROUND: The soluble pattern-recognition receptor known as long pentraxin 3 (PTX3) has a nonredundant role in antifungal immunity. The contribution of single-nucleotide polymorphisms (SNPs) in PTX3 to the development of invasive aspergillosis is unknown. METHODS: We screened an initial cohort of 268 patients undergoing hematopoietic stem-cell transplantation (HSCT) and their donors for PTX3 SNPs modifying the risk of invasive aspergillosis. The analysis was also performed in a multicenter study involving 107 patients with invasive aspergillosis and 223 matched controls. The functional consequences of PTX3 SNPs were investigated in vitro and in lung specimens from transplant recipients. RESULTS: Receipt of a transplant from a donor with a homozygous haplotype (h2/h2) in PTX3 was associated with an increased risk of infection, in both the discovery study (cumulative incidence, 37% vs. 15%; adjusted hazard ratio, 3.08; P = 0.003) and the confirmation study (adjusted odds ratio, 2.78; P = 0.03), as well as with defective expression of PTX3. Functionally, PTX3 deficiency in h2/h2 neutrophils, presumably due to messenger RNA instability, led to impaired phagocytosis and clearance of the fungus. CONCLUSIONS: Genetic deficiency of PTX3 affects the antifungal capacity of neutrophils and may contribute to the risk of invasive aspergillosis in patients treated with HSCT.
AB - BACKGROUND: The soluble pattern-recognition receptor known as long pentraxin 3 (PTX3) has a nonredundant role in antifungal immunity. The contribution of single-nucleotide polymorphisms (SNPs) in PTX3 to the development of invasive aspergillosis is unknown. METHODS: We screened an initial cohort of 268 patients undergoing hematopoietic stem-cell transplantation (HSCT) and their donors for PTX3 SNPs modifying the risk of invasive aspergillosis. The analysis was also performed in a multicenter study involving 107 patients with invasive aspergillosis and 223 matched controls. The functional consequences of PTX3 SNPs were investigated in vitro and in lung specimens from transplant recipients. RESULTS: Receipt of a transplant from a donor with a homozygous haplotype (h2/h2) in PTX3 was associated with an increased risk of infection, in both the discovery study (cumulative incidence, 37% vs. 15%; adjusted hazard ratio, 3.08; P = 0.003) and the confirmation study (adjusted odds ratio, 2.78; P = 0.03), as well as with defective expression of PTX3. Functionally, PTX3 deficiency in h2/h2 neutrophils, presumably due to messenger RNA instability, led to impaired phagocytosis and clearance of the fungus. CONCLUSIONS: Genetic deficiency of PTX3 affects the antifungal capacity of neutrophils and may contribute to the risk of invasive aspergillosis in patients treated with HSCT.
UR - http://www.scopus.com/inward/record.url?scp=84893065011&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84893065011&partnerID=8YFLogxK
U2 - 10.1056/NEJMoa1211161
DO - 10.1056/NEJMoa1211161
M3 - Article
C2 - 24476432
AN - SCOPUS:84893065011
VL - 370
SP - 421
EP - 432
JO - New England Journal of Medicine
JF - New England Journal of Medicine
SN - 0028-4793
IS - 5
ER -