Permissive skin microbiomes in WHIM syndrome: HPV and pathogen expansion

Warts, hypogammaglobulinemia, infections, and myelokathexis syndrome is a rare inborn error of immunity caused by hyperfunctional pathogenic variants in CXCR4, predisposing individuals to recurrent bacterial skin and airway infections and warts. The targeted CXCR4 antagonist plerixafor has shown efficacy in wart regression and a potential reduction in bacterial infection frequency. Here, we investigated the skin microbiomes of 14 patients with warts, hypogammaglobulinemia, infections, and myelokathexis syndrome using shotgun metagenomics, compared with those of healthy controls. Warts, hypogammaglobulinemia, infections, and myelokathexis skin microbial communities displayed greater inter-individual variability, with highly diverse human papillomavirus profiles and an expansion of airway-associated pathogens on the skin. Among patients receiving plerixafor therapy, we observed shifts in the viral composition and a downward trend in viral abundances. Together, these findings demonstrate the distinctive and permissive skin microbiome in warts, hypogammaglobulinemia, infections, and myelokathexis syndrome and highlight the potential microbiome-modulating effects of targeted CXCR4 antagonism.