Journal
JCI INSIGHT
Volume 4, Issue 22, Pages -Publisher
AMER SOC CLINICAL INVESTIGATION INC
DOI: 10.1172/jci.insight.133083
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Funding
- UCSF Nina Ireland Program for Lung Health (NIPLH) Innovative Grant program
- Clinical Sciences Research & Development Service of the VA Office of Research and Development [IK2CX001034]
- Joel D. Cooper Award from the International Society for Heart and Lung Transplantation (ISHLT)
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BACKGROUND. Innate immune activation impacts lung transplant outcomes. Dectin-1 is an innate receptor important for pathogen recognition. We hypothesized that genotypes reducing dectin-1 activity would be associated with infection, graft dysfunction, and death in lung transplant recipients. METHODS. We assessed the rs16910526 CLEC7A gene polymorphism Y238X, which results in dectin-1 truncation, in 321 lung allograft recipients at a single institution and in 1,129 lung allograft recipients in the multicenter Lung Transplant Outcomes Group (LTOG) cohort. Differences in dectin-1 mRNA, cytokines, protein levels, immunophenotypes, and clinical factors were assessed. RESULTS. Y238X carriers had decreased dectin-1 mRNA expression (P = 0.0001), decreased soluble dectin-1 protein concentrations in bronchoalveolar lavage (P = 0.008) and plasma (P = 0.04), and decreased monocyte surface dectin-1 (P = 0.01) compared with wild-type subjects. Y238X carriers had an increased risk of fungal pathogens (HR 1.17, CI 1.0-1.4), an increased risk of graft dysfunction or death (HR 1.6, CI 1.0-2.6), as well increased mortality in the UCSF cohort (HR 1.8, CI 1.1-3.8) and in the LTOG cohort (HR 1.3, CI 1.1-1.6), compared with wild-type CLEC7A subjects. CONCLUSION. Increased rates of graft dysfunction and death associated with this dectin-1 polymorphism may be amplified by immunosuppression that drives higher fungal burden from compromised pathogen recognition.
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