IFNL3/4 polymorphisms are associated with AIDS-related Kaposi’s sarcoma. AIDS
Bibert et al. aimed to analyze whether single nucleotide polymorphisms (SNPs) within the Interferon lambda 3/4 region (IFNL3/4) variants are associated with susceptibility to AIDS-related Kaposi’s sarcoma among men who have sex with men (MSM) enrolled in the Swiss HIV Cohort Study. Of note, SNPs encoding for IFNL3/4 determine different haplotypic combinations (diplotypes) based on their capacity to produce IFNL4, that is, no production versus production as an active P70 or less active S70 form.
Genomic DNA isolated either from blood or cell pellets was genotyped for haplotype tagging SNPs rs8099917 and rs12980275.
Kaposi’s sarcoma was diagnosed in 221 of 2’558 MSM Caucasian participants. Both rs12980275 and rs8099917 were associated with an increased risk of Kaposi’s sarcoma (cumulative incidence 15 versus 10%, P=0.01 and 16 versus 10%, P=.009, respectively). Diplotypes predicted to produce the active P70 form (cumulative incidence 16 versus 10%, P=0.01) but not the less active S70 (cumulative incidence 11 versus 10%, P=0.7) form of IFNL4 were associated with an increased risk of Kaposi’s sarcoma, compared with those predicted not to produce IFNL4. The associations remained significant in a multivariate Cox regression model after adjustment for age at infection, combination antiretroviral therapy, median CD4+ T-cell count nadir and CD4+ slopes (hazard ratio 1.42, 95% confidence interval 1.06–1.89, P=0.02 for IFLN P70 versus no IFNL4).
In summary, the data show an association between IFNL3/4 polymorphisms and the development of Kaposi’s sarcoma among HIV+ MSM patients. This new finding confirms that IFNLs mediate antiviral responses against a growing range of viruses.