CD70 deficiency due to a novel mutation in a patient with severe chronic EBV infection presenting as a periodic fever

Roberta Caorsi, Marta Rusmini, Stefano Volpi, Sabrina Chiesa, Claudia Pastorino, Angela Rita Sementa, Paolo Uva, Alice Grossi, Edoardo Lanino, Maura Faraci, Francesca Minoia, Sara Signa, Paolo Picco, Alberto Martini, Isabella Ceccherini, Marco Gattorno

Research output: Contribution to journalArticlepeer-review


Primary immunodeficiencies with selective susceptibility to EBV infection are rare conditions associated with severe lymphoproliferation. We followed a patient, son of consanguineous parents, referred to our center for recurrent periodic episodes of fever associated with tonsillitis and adenitis started after an infectious mononucleosis and responsive to oral steroid. An initial diagnosis of periodic fever, aphthous stomatitis, pharyngitis, cervical adenitis syndrome was done. In the following months, recurrent respiratory infections and episodes of keratitis were also observed, together with a progressive reduction of immunoglobulin levels and an increase of CD20+ cells. Cell sorting and EBV PCR showed 25,000 copies for 100,000 leukocytes with predominant infection of B lymphocytes. Lymph node's biopsy revealed reactive lymphadenopathy with paracortical involvement consistent with a chronic EBV infection. Molecular analysis of XIAP, SHA2D1A, ITK, and CD27 genes did not detect any pathogenic mutation. The patients underwent repeated courses of anti-CD20 therapy with only a partial control of the disease, followed by stem cell transplantation with a complete normalization of clinical and immunological features. Whole exome sequencing of the trio was performed. Among the variants identified, a novel loss of function homozygous c.163-2A > G mutation of the CD70 gene, affecting the exon 2 AG-acceptor splice site, fit the expected recessive model of inheritance. Indeed, deficiency of both CD27, and, more recently, of its ligand CD70, has been reported as a cause of EBV-driven lymphoproliferation and hypogammaglobulinemia. Cell surface analysis of patient-derived PHA-T cell blasts and EBV-transformed lymphoblastoid cell lines confirmed absence of CD70 expression. In conclusion, we describe a case of severe chronic EBV infection caused by a novel mutation of CD70 presenting with recurrent periodic fever.

Original languageEnglish
Article number2015
JournalFrontiers in Immunology
Issue numberJAN
Publication statusPublished - Jan 29 2018


  • Aphthous stomatitis
  • CD70 deficiency
  • Cervical adenitis syndrome
  • Ebstein-Barr virus
  • Hematopoietic stem cell transplantation
  • Periodic fever
  • Pharyngitis

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology


Dive into the research topics of 'CD70 deficiency due to a novel mutation in a patient with severe chronic EBV infection presenting as a periodic fever'. Together they form a unique fingerprint.

Cite this