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01-10-2017 | Original Article

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

Authors: 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 Korganow, the DEFI study group

Published in: Journal of Clinical Immunology | Issue 7/2017

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 CD21^low CD38^low 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.

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Title: Neutropenia in Patients with Common Variable Immunodeficiency: a Rare Event Associated with Severe Outcome
Authors: 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 Korganow
the DEFI study group
Publication date: 01-10-2017
Publisher: Springer US
Published in: Journal of Clinical Immunology / Issue 7/2017
Print ISSN: 0271-9142
Electronic ISSN: 1573-2592
DOI: https://doi.org/10.1007/s10875-017-0434-2

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Abstract

Background

Methods

Results

Conclusion

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