Journal of Clinical Immunology

, Volume 33, Issue 1, pp 14–21 | Cite as

EVER2 Deficiency is Associated with Mild T-cell Abnormalities

  • Amandine Crequer
  • Capucine Picard
  • Vincent Pedergnana
  • Annick Lim
  • Shen-Ying Zhang
  • Laurent Abel
  • Slawomir Majewski
  • Jean-Laurent Casanova
  • Stefania Jablonska
  • Gerard Orth
  • Emmanuelle Jouanguy
Original Research


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.


Epidermodysplasia 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.

Supplementary material

10875_2012_9749_Fig3_ESM.jpg (51 kb)
Esm 1

EVER2-deficient patients have an increase of CCR10+CD4+ T cells. Skin-homing T-cell subsets were assessed on live CD3+-gated cryopreserved PBMCs from the two patients (P1 values indicated by gray diamonds, P2 values indicated by gray squares, P3 values indicated by gray up triangles) and healthy controls (indicated by black circles) by flow cytometry (a) CCR6+, (b) CCR4+ and (c) CCR10+ proportions were assessed on live CD3+, CD4+ and CD8+ gated PBMCs for the patients and 17, 12 and 12 healthy controls, respectively. (* = p <0.05; ns = non significant). (JPEG 50 kb)

10875_2012_9749_MOESM1_ESM.tif (1 mb)
High resolution image (TIFF 1.03 MB)
10875_2012_9749_Fig4_ESM.jpg (52 kb)
Esm 2

EVER2-deficient patients have normal frequencies of αE+, α4+ and β7+ T cells. Tissue-homing T-cell subsets were assessed on live CD3+-gated cryopreserved PBMCs from the two patients (P1 values indicated by gray diamonds, P2 values indicated by gray squares, P3 values indicated by gray up triangles) and healthy controls (indicated by black circles) by flow cytometry (a) αE+, (b) αE+CLA+ proportions were assessed on live CD3+, CD4+ and CD8+ gated PBMCs and 12, 17 and 12 healthy controls, respectively (c) α4+, β7+ and α4+β7+ proportions were assessed on live CD3+ gated PBMCs for the patients and 12 healthy controls, respectively. ns = non significant). (JPEG 52 kb)

10875_2012_9749_MOESM2_ESM.tif (1014 kb)
High resolution image (TIFF 0.99 MB)


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Copyright information

© Springer Science+Business Media, LLC 2012

Authors and Affiliations

  • Amandine Crequer
    • 1
    • 4
  • Capucine Picard
    • 2
    • 3
    • 4
  • Vincent Pedergnana
    • 2
    • 4
  • Annick Lim
    • 5
  • Shen-Ying Zhang
    • 1
    • 2
  • Laurent Abel
    • 1
    • 2
    • 4
  • Slawomir Majewski
    • 6
  • Jean-Laurent Casanova
    • 1
    • 2
    • 4
    • 7
  • Stefania Jablonska
    • 8
  • Gerard Orth
    • 9
  • Emmanuelle Jouanguy
    • 1
    • 2
    • 4
  1. 1.St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller BranchThe Rockefeller UniversityNew YorkUSA
  2. 2.Laboratory of Human Genetics of Infectious Diseases, Necker BranchINSERM U980ParisFrance
  3. 3.Study Center of Primary ImmunodeficienciesNecker Hospital, AP-HPParisFrance
  4. 4.Paris Descartes UniversityParisFrance
  5. 5.Department of ImmunologyPasteur InstituteParisFrance
  6. 6.Department of Dermatology and VenereologyCenter of Diagnostics and Treatment of STD at Warsaw Medical UniversityWarsawPoland
  7. 7.Pediatric Immuno-hematology UnitNecker Hospital, AP-HPParisFrance
  8. 8.Department of DermatologyWarsaw School of MedecineWarsawPoland
  9. 9.Department of VirologyPasteur InstituteParisFrance

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