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Journal of Clinical Immunology

, Volume 37, Issue 7, pp 715–726 | Cite as

Neutropenia in Patients with Common Variable Immunodeficiency: a Rare Event Associated with Severe Outcome

  • Aurélien Guffroy
  • Rachel Mourot-Cottet
  • Laurence Gérard
  • Vincent Gies
  • Chantal Lagresle
  • Aurore Pouliet
  • Patrick Nitschké
  • Sylvain Hanein
  • Boris Bienvenu
  • Valérie Chanet
  • Jean Donadieu
  • Martine Gardembas
  • Marina Karmochkine
  • Raphaele Nove-Josserand
  • Thierry Martin
  • Vincent Poindron
  • Pauline Soulas-Sprauel
  • Fréderic Rieux-Laucat
  • Claire Fieschi
  • Eric Oksenhendler
  • Isabelle André-Schmutz
  • Anne-Sophie KorganowEmail author
  • the DEFI study group
Original Article

Abstract

Background

Common variable immunodeficiency (CVID) is characterized by infections and hypogammaglobulinemia. Neutropenia is rare during CVID.

Methods

The French DEFI study enrolled patients with primary hypogammaglobulinemia. Patients with CVID and neutropenia were retrospectively analyzed.

Results

Among 473 patients with CVID, 16 patients displayed neutropenia (lowest count [0–1400]*106/L). Sex ratio (M/F) was 10/6. Five patients died during the follow-up (11 years) with an increased percentage of deaths compared to the whole DEFI group (31.3 vs 3.4%, P < 0.05). Neutropenia was diagnosed for 10 patients before 22 years old. The most frequent symptoms, except infections, were autoimmune cytopenia, i.e., thrombopenia or anemia (11/16). Ten patients were affected with lymphoproliferative diseases. Two patients were in the infection only group and the others belonged to one or several other CVID groups. The median level of IgG was 2.6 g/L [0.35–4.4]. Most patients presented increased numbers of CD21low CD38low B cell, as already described in CVID autoimmune cytopenia group. Neutropenia was considered autoimmune in 11 cases. NGS for 52 genes of interest was performed on 8 patients. No deleterious mutations were found in LRBA, CTLA4, and PIK3. More than one potentially damaging variant in other genes associated with CVID were present in most patients arguing for a multigene process.

Conclusion

Neutropenia is generally associated with another cytopenia and presumably of autoimmune origin during CVID. In the DEFI study, neutropenia is coupled with more severe clinical outcomes. It appears as an “alarm bell” considering patients’ presentation and the high rate of deaths. Whole exome sequencing diagnosis should improve management.

Keywords

Neutropenia Autoimmune cytopenia Common variable immunodeficiency (CVID) Next genome sequencing 

Abbreviations

AC

Autoimmune cytopenia

AIHA

Autoimmune hemolytic anemia

AIN

Autoimmune neutropenia

CVID

Common variable immuno-deficiency

ENT

Ears, nose, and throat

GAT

Granulocyte aggregation test

GIFT

Granulocyte immunofluorescence test

HNA

Human neutrophil antigen

ITP

Idiopathic thrombocytopenic purpura

LOCID

Late-onset combined immunodeficiency

LP

Lymphoproliferation

MAIGA

Monoclonal antibody immobilization of granulocyte antigen

OS

Overall survival

Notes

Authorsʼ Contribution

A.G., R.M-C., L.G., C.F, E.O., A.S.K designed the research.

A.G., R.M-C, L.G., B.B., V.C., J.D., M.G., M.K., R.N-J., T.M, V.P, P.S-S, C.F, E.O, and A.S.K performed the research.

A.G, R.M-C., V.G, C.L, A.P, F.R-L, I.A-S, and A.S.K. analyzed the data.

A.G., R.M-C., V.G., I.A-S, and A.S.K. wrote the paper.

All the authors read and approve the final manuscript.

Funding

APJC (appel à projet jeune chercheur) DICEP GIRCI Grand Est 2016.

RARENET co-financed by the ERDF of the EU in the framework of the INTERREG V Upper Rhine program.

Compliance with Ethical Standards

Conflict of Interest

The authors declare that they have no conflicts of interest.

Supplementary material

10875_2017_434_MOESM1_ESM.docx (195 kb)
ESM 1 (DOCX 194 kb)

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Copyright information

© Springer Science+Business Media, LLC 2017

Authors and Affiliations

  • Aurélien Guffroy
    • 1
    • 2
  • Rachel Mourot-Cottet
    • 3
  • Laurence Gérard
    • 4
    • 5
  • Vincent Gies
    • 1
    • 2
  • Chantal Lagresle
    • 6
  • Aurore Pouliet
    • 7
  • Patrick Nitschké
    • 8
  • Sylvain Hanein
    • 9
  • Boris Bienvenu
    • 10
  • Valérie Chanet
    • 11
  • Jean Donadieu
    • 12
  • Martine Gardembas
    • 13
  • Marina Karmochkine
    • 14
  • Raphaele Nove-Josserand
    • 15
  • Thierry Martin
    • 1
    • 2
  • Vincent Poindron
    • 1
  • Pauline Soulas-Sprauel
    • 1
    • 2
  • Fréderic Rieux-Laucat
    • 16
  • Claire Fieschi
    • 4
    • 5
  • Eric Oksenhendler
    • 4
    • 5
  • Isabelle André-Schmutz
    • 6
  • Anne-Sophie Korganow
    • 1
    • 2
    Email author
  • the DEFI study group
  1. 1.Department of Clinical Immunology and Internal MedicineStrasbourg University Hospital, National Reference Center for Autoimmune DiseasesStrasbourgFrance
  2. 2.CNRS UPR 3572 Immunopathology and Therapeutic Chemistry/Laboratory of Excellence MedalisInstitute of Molecular and Cellular Biology (IBMC)StrasbourgFrance
  3. 3.Department of Internal Medicine BStrasbourg University HospitalStrasbourgFrance
  4. 4.Department of Clinical Immunology, Saint-Louis HospitalAssistance Publique Hôpitaux de Paris (APHP)ParisFrance
  5. 5.EA3518Université Paris Diderot Paris 7ParisFrance
  6. 6.INSERM UMR 1163 Human Lympho Hematopopoiesis LaboratoryParis Descartes Sorbonne Paris Cite University, Imagine InstituteParisFrance
  7. 7.INSERM UMR 1163 Bioinformatic PlatformParis Descartes Sorbonne Paris Cite University, Imagine InstituteParisFrance
  8. 8.INSERM UMR 1163 Genomic PlatformParis Descartes Sorbonne Paris Cite University, Imagine InstituteParisFrance
  9. 9.INSERM UMR 1163 Translational Genetic PlatformParis Descartes Sorbonne Paris Cite University, Imagine InstituteParisFrance
  10. 10.Department of Internal MedicineCaen University HospitalCaenFrance
  11. 11.Department of Internal MedicineCabinet de Médecine Interne et Maladies Infectieuses, Pôle Santé RépubliqueClermont-FerrandFrance
  12. 12.Department of Pediatric Hematology and Oncology, Hôpital d’enfants Armand-TrousseauParis University HospitalParisFrance
  13. 13.Department of HematologyAngers University HospitalAngersFrance
  14. 14.Department of Clinical Immunology, European Hospital Georges PompidouParis University HospitalParisFrance
  15. 15.Department of Internal MedicineLyon University HospitalPierre-BéniteFrance
  16. 16.INSERM UMR 1163 Immunogenetics of pediatric autoimmune diseases laboratoryParis Descartes Sorbonne Paris Cite University, Imagine InstituteParisFrance

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