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Genetic Predisposition and Aspergillosis in Stem-Cell Transplant Recipients

Summary and Comment |
January 29, 2014

Genetic Predisposition and Aspergillosis in Stem-Cell Transplant Recipients

  1. Larry M. Baddour, MD

PTX3 deficiency may increase the risk for invasive aspergillosis in hematopoietic stem-cell transplant recipients.

  1. Larry M. Baddour, MD

Animal infection models have suggested that the protein long pentraxin 3 (PTX3) is important in antifungal immunity. In a recent study, researchers screened patients undergoing allogeneic hematopoietic stem-cell transplantation (HSCT) and their donors for single-nucleotide polymorphisms (SNPs) in the PTX3 gene to determine whether certain SNPs were associated with increased risk for developing invasive aspergillosis (IA).

Two different patient populations were screened for SNPs: 268 adult patients with hematologic disorders who were undergoing allogeneic HSCT — and their respective donors — from one medical center in Italy (discovery cohort), and 107 HSCT patients with proven or probable IA at various medical centers in Europe and 223 matched controls (confirmation cohort).

A homozygous haplotype, h2/h2, in PTX3 was associated with increased risk for IA in both the discovery cohort (cumulative incidence, 37% vs. 15%; adjusted hazard ratio, 3.08; 95% confidence interval,1.47–6.44) and the confirmation cohort (adjusted odds ratio, 2.78; 95% CI, 1.22–8.93).

In vitro studies demonstrated that neutrophils from h2/h2 patients had impaired phagocytosis of Aspergillus fumigatus conidia and a decrease in conidiocidal activity. The addition of PTX3 enhanced both phagocytosis and conidiocidal activity.

Comment

These findings provide further support for a role of long pentraxin 3 in host defense. Might similar investigations ultimately improve our ability to define a subpopulation at risk for opportunistic infections — in this case, invasive aspergillosis — and aid us in developing optimal prevention strategies?

  • Disclosures for Larry M. Baddour, MD at time of publication Editorial boards UpToDate Leadership positions in professional societies American Heart Association (Chairman, Rheumatic Fever, Endocarditis, Kawasaki Disease Committee)

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