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

Area of Science:

• Immunogenetics
• Transplant Medicine
• Infectious Disease Epidemiology

Background:

• Single-nucleotide polymorphisms (SNPs) in immune genes are linked to invasive mold infection (IMI) susceptibility in hematopoietic stem cell transplant recipients.
• This association has not been clearly established in solid-organ transplant (SOT) recipients.

Purpose of the Study:

• To investigate the association between specific genetic polymorphisms and the risk of mold colonization and invasive mold infection (IMI) in SOT recipients.
• To explore the functional impact of these polymorphisms on immune responses.

Main Methods:

• Genotyping of 24 SNPs in immune genes among 1101 SOT recipients from the Swiss Transplant Cohort Study.
• Association analysis using log-rank test and Cox regression models.
• Measurement of cytokine production (IL-1β, TNF-α) upon Aspergillus stimulation in peripheral blood mononuclear cells (PBMCs) and correlation with genotypes.

Main Results:

• Polymorphisms in interleukin 1β (IL1B; rs16944), interleukin 1 receptor antagonist (IL1RN; rs419598), and β-defensin 1 (DEFB1; rs1800972) were significantly associated with mold colonization and IMI.
• The associations for IL1B (rs16944) and DEFB1 (rs1800972) remained significant in multivariate analysis.
• Carriage of two copies of the rare allele for rs16944 or rs419598 was linked to reduced Aspergillus-induced IL-1β and TNF-α secretion.

Conclusions:

• Functional polymorphisms in IL1B and DEFB1 genes play a role in determining susceptibility to mold infections in SOT recipients.
• These findings may facilitate individual risk stratification for mold infections in SOT patients.