CD70 Deficiency due to a Novel Mutation in a Patient with Severe Chronic EBV Infection Presenting As a Periodic Fever
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 sta...
Main Authors: | , , , , , , , , , , , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
Frontiers Media S.A.
2018-01-01
|
Series: | Frontiers in Immunology |
Subjects: | |
Online Access: | http://journal.frontiersin.org/article/10.3389/fimmu.2017.02015/full |
id |
doaj-b2bdffbf61a248c1a7973c27c4011b96 |
---|---|
record_format |
Article |
spelling |
doaj-b2bdffbf61a248c1a7973c27c4011b962020-11-24T21:24:41ZengFrontiers Media S.A.Frontiers in Immunology1664-32242018-01-01810.3389/fimmu.2017.02015308875CD70 Deficiency due to a Novel Mutation in a Patient with Severe Chronic EBV Infection Presenting As a Periodic FeverRoberta Caorsi0Marta Rusmini1Stefano Volpi2Sabrina Chiesa3Claudia Pastorino4Angela Rita Sementa5Paolo Uva6Alice Grossi7Edoardo Lanino8Maura Faraci9Francesca Minoia10Sara Signa11Paolo Picco12Alberto Martini13Isabella Ceccherini14Marco Gattorno15Clinica Pediatria e Reumatologia, Istituto Giannina Gaslini, Genova, ItalyDivision of Human Genetics, Istituto Giannina Gaslini, Genova, ItalyClinica Pediatria e Reumatologia, Istituto Giannina Gaslini, Genova, ItalyClinica Pediatria e Reumatologia, Istituto Giannina Gaslini, Genova, ItalyClinica Pediatria e Reumatologia, Istituto Giannina Gaslini, Genova, ItalyPathology Unit, Istituto Giannina Gaslini, Genova, ItalyCentre for Advanced Studies, Research and Development in Sardinia (CRS4), Science and Technology Park Polaris, Pula, ItalyDivision of Human Genetics, Istituto Giannina Gaslini, Genova, ItalyBone Marrow Transplantation Unit, Istituto Giannina Gaslini, Genova, ItalyBone Marrow Transplantation Unit, Istituto Giannina Gaslini, Genova, ItalyClinica Pediatria e Reumatologia, Istituto Giannina Gaslini, Genova, ItalyClinica Pediatria e Reumatologia, Istituto Giannina Gaslini, Genova, ItalyClinica Pediatria e Reumatologia, Istituto Giannina Gaslini, Genova, ItalyClinica Pediatria e Reumatologia, Istituto Giannina Gaslini, Genova, ItalyDivision of Human Genetics, Istituto Giannina Gaslini, Genova, ItalyClinica Pediatria e Reumatologia, Istituto Giannina Gaslini, Genova, ItalyPrimary 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.http://journal.frontiersin.org/article/10.3389/fimmu.2017.02015/fullCD70 deficiencyperiodic feveraphthous stomatitispharyngitiscervical adenitis syndromeperiodic fever |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
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 |
spellingShingle |
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 CD70 Deficiency due to a Novel Mutation in a Patient with Severe Chronic EBV Infection Presenting As a Periodic Fever Frontiers in Immunology CD70 deficiency periodic fever aphthous stomatitis pharyngitis cervical adenitis syndrome periodic fever |
author_facet |
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 |
author_sort |
Roberta Caorsi |
title |
CD70 Deficiency due to a Novel Mutation in a Patient with Severe Chronic EBV Infection Presenting As a Periodic Fever |
title_short |
CD70 Deficiency due to a Novel Mutation in a Patient with Severe Chronic EBV Infection Presenting As a Periodic Fever |
title_full |
CD70 Deficiency due to a Novel Mutation in a Patient with Severe Chronic EBV Infection Presenting As a Periodic Fever |
title_fullStr |
CD70 Deficiency due to a Novel Mutation in a Patient with Severe Chronic EBV Infection Presenting As a Periodic Fever |
title_full_unstemmed |
CD70 Deficiency due to a Novel Mutation in a Patient with Severe Chronic EBV Infection Presenting As a Periodic Fever |
title_sort |
cd70 deficiency due to a novel mutation in a patient with severe chronic ebv infection presenting as a periodic fever |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Immunology |
issn |
1664-3224 |
publishDate |
2018-01-01 |
description |
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. |
topic |
CD70 deficiency periodic fever aphthous stomatitis pharyngitis cervical adenitis syndrome periodic fever |
url |
http://journal.frontiersin.org/article/10.3389/fimmu.2017.02015/full |
work_keys_str_mv |
AT robertacaorsi cd70deficiencyduetoanovelmutationinapatientwithseverechronicebvinfectionpresentingasaperiodicfever AT martarusmini cd70deficiencyduetoanovelmutationinapatientwithseverechronicebvinfectionpresentingasaperiodicfever AT stefanovolpi cd70deficiencyduetoanovelmutationinapatientwithseverechronicebvinfectionpresentingasaperiodicfever AT sabrinachiesa cd70deficiencyduetoanovelmutationinapatientwithseverechronicebvinfectionpresentingasaperiodicfever AT claudiapastorino cd70deficiencyduetoanovelmutationinapatientwithseverechronicebvinfectionpresentingasaperiodicfever AT angelaritasementa cd70deficiencyduetoanovelmutationinapatientwithseverechronicebvinfectionpresentingasaperiodicfever AT paolouva cd70deficiencyduetoanovelmutationinapatientwithseverechronicebvinfectionpresentingasaperiodicfever AT alicegrossi cd70deficiencyduetoanovelmutationinapatientwithseverechronicebvinfectionpresentingasaperiodicfever AT edoardolanino cd70deficiencyduetoanovelmutationinapatientwithseverechronicebvinfectionpresentingasaperiodicfever AT maurafaraci cd70deficiencyduetoanovelmutationinapatientwithseverechronicebvinfectionpresentingasaperiodicfever AT francescaminoia cd70deficiencyduetoanovelmutationinapatientwithseverechronicebvinfectionpresentingasaperiodicfever AT sarasigna cd70deficiencyduetoanovelmutationinapatientwithseverechronicebvinfectionpresentingasaperiodicfever AT paolopicco cd70deficiencyduetoanovelmutationinapatientwithseverechronicebvinfectionpresentingasaperiodicfever AT albertomartini cd70deficiencyduetoanovelmutationinapatientwithseverechronicebvinfectionpresentingasaperiodicfever AT isabellaceccherini cd70deficiencyduetoanovelmutationinapatientwithseverechronicebvinfectionpresentingasaperiodicfever AT marcogattorno cd70deficiencyduetoanovelmutationinapatientwithseverechronicebvinfectionpresentingasaperiodicfever |
_version_ |
1725986774270869504 |