IL1B and DEFB1 Polymorphisms Increase Susceptibility to Invasive Mold Infection After Solid Organ Transplantation.

Wójtowicz, A; Gresnigt, M S; Lecompte, T; Bibert, S; Manuel, O; Joosten, L A B; Rüeger, S; Berger, C; Boggian, K; Cusini, Alexia; Garzoni, Christian; Hirsch, H H; Weisser, M; Mueller, N J; Meylan, P R; Steiger, Jürg; Kutalik, Z; Pascual, M; van Delden, C; van de Veerdonk, F L; ... (2015). IL1B and DEFB1 Polymorphisms Increase Susceptibility to Invasive Mold Infection After Solid Organ Transplantation. Journal of infectious diseases, 211(10), pp. 1646-1657. Oxford University Press 10.1093/infdis/jiu636

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BACKGROUND  Single nucleotide polymorphisms (SNPs) in immune genes have been associated with susceptibility to invasive mold infection (IMI) among hematopoietic stem cell (HSCT) but not solid organ transplant (SOT) recipients. METHODS  24 SNPs from systematically selected genes were genotyped among 1101 SOT recipients (715 kidneys, 190 liver, 102 lungs, 79 hearts, 15 other) from the Swiss Transplant Cohort Study. Association between SNPs and the endpoint were assessed by log-rank test and Cox regression models. Cytokine production upon Aspergillus stimulation was measured by ELISA in PBMCs from healthy volunteers and correlated with relevant genotypes. RESULTS  Mold colonization (N=45) and proven/probable IMI (N=26) were associated with polymorphisms in interleukin-1 beta (IL1B, rs16944; log-rank test, recessive mode, colonization P=0.001 and IMI P=0.00005), interleukin-1 receptor antagonist (IL1RN, rs419598; P=0.01 and P=0.02) and β-defensin-1 (DEFB1, rs1800972; P=0.001 and P=0.0002, respectively). The associations with IL1B and DEFB1 remained significant in a multivariate regression model (IL1B rs16944 P=0.002; DEFB1 rs1800972 P=0.01). Presence of two copies of the rare allele of rs16944 or rs419598 was associated with reduced Aspergillus-induced IL-1β and TNFα secretion by PBMCs. CONCLUSIONS  Functional polymorphisms in IL1B and DEFB1 influence susceptibility to mold infection in SOT recipients. This observation may contribute to individual risk stratification.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Department of Haematology, Oncology, Infectious Diseases, Laboratory Medicine and Hospital Pharmacy (DOLS) > Clinic of Infectiology

UniBE Contributor:

Cusini, Alexia; Garzoni, Christian and Steiger, Jürg

Subjects:

600 Technology > 610 Medicine & health

ISSN:

0022-1899

Publisher:

Oxford University Press

Language:

English

Submitter:

Annelies Luginbühl

Date Deposited:

03 Dec 2014 16:10

Last Modified:

23 Oct 2019 05:35

Publisher DOI:

10.1093/infdis/jiu636

PubMed ID:

25398456

BORIS DOI:

10.7892/boris.60176

URI:

https://boris.unibe.ch/id/eprint/60176

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