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PTX3 deficiency may increase aspergillosis risk in HSCT recipients
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In patients undergoing hematopoietic stem cell transplantation, a deficiency of the PTX3 gene may increase the risk for invasive aspergillosis, according to results of a recent study.
In an initial discovery study, the researchers analyzed 268 patients with hematologic disorders who underwent hematopoietic stem cell transplantation (HSCT) at the Hospital of the University of Perugia in Italy, and their donors. These patients were screened for PTX3 single nucleotide polymorphisms, and the cumulative incidence method was used to determine the probability of invasive aspergillosis according to PTX3 polymorphisms.
The analysis also was conducted through a multicenter confirmation study, which included 107 patients with invasive Aspergillus fumigatus infection and a matched control group (n=223). The confirmation study evaluated not only transplant recipients from related donors, but also those from unrelated donors.
In vitro and lung samples from transplant recipients were evaluated to determine the influence of PTX3 single nucleotide polymorphisms.
The researchers found that transplants from donors with a homozygous haplotype (h2/h2) in PTX3 conferred increased risk for infection. This effect was observed in both the discovery study (cumulative incidence, 37% vs. 15%; adjusted HR=3.08; P=.003) and the confirmation study (adjusted OR=2.78; P=.03). Transplants from these donors also were associated with impaired expression of PTX3. Deficiencies in PTX3 in h2/h2 neutrophils led to defective phagocytosis, most likely due to instability of messenger RNA. This, in turn, led to impaired clearance of the fungus.
“In this study, we found an association between donor h2/h2 haplotype in PTX3 and invasive aspergillosis in patients undergoing HSCT, a finding that supports the nonredundant role of PTX3 in host defense against A. fumigatus,” the researchers wrote. “More important, the increased risk of infection was observed regardless of the human leukocyte antigen-matching status of the donor, T-cell manipulation, and acute graft-versus-host disease and prophylaxis, further sustaining a potentially independent contribution of PTX3 variants to the development and outcome of invasive aspergillosis in the context of various strategies for modulating lymphocyte function.”
Disclosure: See the study for a full list of researchers’ financial disclosures.
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