ATYPICAL PRESENTATION OF X-LINKED IL-2 RECEPTOR GAMMA MUTATION CHARACTERIZED BY RECURRENT CUTANEOUS AND GENITAL WARTS

Abstract

<h3>Introduction</h3> Combined immunodeficiency syndromes constitute a group of inherited immune disorders characterized by diminished lymphocyte number and function. Late onset combined immunodeficiency can be difficult to diagnose as patients initially have a less severe phenotype compared to their SCID counterparts. Here we describe a case of an atypical presentation of late onset combined immunodeficiency due to a hemizygous IL-2 receptor gamma (IL-2Rg) mutation. <h3>Case</h3> The patient is a 41-year-old male with a 25-year history of recurrent cutaneous warts of the hands and feet. At the age of 36 he developed perianal condylomata acuminata that later developed into squamous cell carcinoma. He reported no history of recurrent sinopulmonary infection, atopic disease, or autoimmunity. Immune phenotyping demonstrated normal B- and NK cell counts but CD4+ T-cell lymphopenia with poor proliferation to antigenic stimulation. Total immunoglobulins were normal but without vaccine responses. Genetic testing revealed a hemizygous variant of unknown significance in IL2Rg gene. NK cell cytotoxicity assay showed suboptimal cytotoxicity and CD8+ T-cells exhibited impaired pSTAT5 confirming the likely pathogenicity of this variant. <h3>Discussion</h3> IL-2 plays a critical role in the activation among a host of T-cells and NK cells. Deleterious mutations of the IL-2Rg gene are associated with X-linked SCID displaying a T−B+NK− phenotype. Milder phenotypes have been reported with hypomorphic mutations of IL-2Rg, with a recent report describing recurrent cutaneous warts and respiratory infections in two brothers with splice site mutations. This patient's chronic HPV infection resulted in malignant sequalae, highlighting the importance for awareness of the phenotypic heterogeneity that can occur in X-linked SCID.