EVER2 Deficiency is Associated with Mild T-cell Abnormalities
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Epidermodysplasia verruciformis (EV) is a rare genodermatosis characterized by persistent flat warts or pityriasis versicolor-like lesions caused by betapapillomaviruses (EV-HPVs). Autosomal recessive EVER1 and EVER2 deficiencies account for EV in most patients. The mechanisms by which mutations in these partners of the Zinc transporter ZnT1 impair host defense against EV-HPVs are still poorly understood. Keratinocytes of EVER-deficient patients display an alteration of zinc homeostasis and an enhanced proliferative activity. Since EVER proteins are highly expressed in T lymphocytes, we aimed to assess the impact of EVER2 deficiency on T-cell development and function. We studied circulating lymphocyte populations in three adult EV patients sharing the same EVER2 mutation (T150fsX3). We found a normal count of CD4+ and CD8+ T cells and a normal proliferative capacity in response to anti-CD3 stimulation. However, we observed a significant increase of memory CD4+ and effector memory CD8+ T cells, a bias of the TCR Vαβ and Vγδ repertoires and an increase of skin-homing CD4+ T-cell subsets. Our findings suggest that EVER2-deficient patients display mild T-cell abnormalities. It remains unclear whether these abnormalities result from EVER deficiency, chronic EV-HPV infection, or both.
KeywordsEpidermodysplasia verruciformis EVER immune deficiencies T cells
We thank the members of both branches of the Saint Giles Laboratory of Human Genetics of Infectious Diseases, but also Aminata Diabate, Corinne Jacques, Chantal Harre and Stephanie N’Daga for excellent technical assistance, and Svetlana Mazel for flow cytometry expertise. We warmly thank the patients for their participation. This work was supported by grants from INSERM, University Paris Descartes, the Rockefeller University, the St. Giles Foundation, and the Rockefeller University Center for Clinical and Translational Science grant number UL1RR024143.
Competing interest statement
The authors declare that they have no competing financial interests.
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