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J Clin Immunol. 2017 Oct;37(7):715-726. doi: 10.1007/s10875-017-0434-2. Epub 2017 Aug 26.

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

Author information

1
Department of Clinical Immunology and Internal Medicine, Strasbourg University Hospital, National Reference Center for Autoimmune Diseases, Strasbourg, France.
2
CNRS UPR 3572 Immunopathology and Therapeutic Chemistry/Laboratory of Excellence Medalis, Institute of Molecular and Cellular Biology (IBMC), Strasbourg, France.
3
Department of Internal Medicine B, Strasbourg University Hospital, Strasbourg, France.
4
Department of Clinical Immunology, Saint-Louis Hospital, Assistance Publique Hôpitaux de Paris (APHP), Paris, France.
5
EA3518, Université Paris Diderot Paris 7, Paris, France.
6
INSERM UMR 1163 Human Lympho Hematopopoiesis Laboratory, Paris Descartes Sorbonne Paris Cite University, Imagine Institute, Paris, France.
7
INSERM UMR 1163 Bioinformatic Platform, Paris Descartes Sorbonne Paris Cite University, Imagine Institute, Paris, France.
8
INSERM UMR 1163 Genomic Platform, Paris Descartes Sorbonne Paris Cite University, Imagine Institute, Paris, France.
9
INSERM UMR 1163 Translational Genetic Platform, Paris Descartes Sorbonne Paris Cite University, Imagine Institute, Paris, France.
10
Department of Internal Medicine, Caen University Hospital, Caen, France.
11
Department of Internal Medicine, Cabinet de Médecine Interne et Maladies Infectieuses, Pôle Santé République, Clermont-Ferrand, France.
12
Department of Pediatric Hematology and Oncology, Hôpital d'enfants Armand-Trousseau, Paris University Hospital, Paris, France.
13
Department of Hematology, Angers University Hospital, Angers, France.
14
Department of Clinical Immunology, European Hospital Georges Pompidou, Paris University Hospital, Paris, France.
15
Department of Internal Medicine, Lyon University Hospital, Pierre-Bénite, France.
16
INSERM UMR 1163 Immunogenetics of pediatric autoimmune diseases laboratory, Paris Descartes Sorbonne Paris Cite University, Imagine Institute, Paris, France.
17
Department of Clinical Immunology and Internal Medicine, Strasbourg University Hospital, National Reference Center for Autoimmune Diseases, Strasbourg, France. korganow@unistra.fr.
18
CNRS UPR 3572 Immunopathology and Therapeutic Chemistry/Laboratory of Excellence Medalis, Institute of Molecular and Cellular Biology (IBMC), Strasbourg, France. korganow@unistra.fr.

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:

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

PMID:
28842786
DOI:
10.1007/s10875-017-0434-2
[Indexed for MEDLINE]

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