491 Recalcitrant cutaneous warts in a family with inherited ICOS deficiency

Recalcitrant warts (RW), caused by human papillomaviruses (HPVs), can be a cutaneous manifestation of inborn error immunity. This study investigated the clinical manifestations, immunodeficiency, single-gene susceptibility, and HPV repertoire in consanguineous family with severe sinopulmonary infections RWs. Clinical immunological evaluations, including fluorescence-activated cell-sorting lymphocyte-transformation test, provided evidence for immunodeficiency. Combined whole-exome sequencing genome-wide homozygosity mapping was utilized to disclose candidate sequence variants. Whole-transcriptome (RNA-Seq) used concomitantly investigate genotypes consequences detected variants host. The proband, 41-year-old male, found homozygous c.6delG, p.Lys2Asnfs*17 variant ICOS, encoding inducible T cell co-stimulator. located inside 5 Mb runs on 2q33.2. RNA-Seq confirmed deleteriousness ICOS three skin biopsies revealing significant downregulation its ligand, ICOSLG. Reads unaligned genome were applied 926 different viruses, α-HPV57, β-HPV107, β-HPV14 β-HPV17 detected. Collectively, we describe previously unrecognized immunity HPVs, indicating that autosomal recessive deficiency underlie RWs, emphasizing underpinnings RWs at nexus viral genomic variation.