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

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.

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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

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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.

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Contributions

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.

Corresponding author

Correspondence to Anne-Sophie Korganow.

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The authors declare that they have no conflicts of interest.

Additional information

Aurélien Guffroy and Rachel Mourot-Cottet contribute equally to the work.

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Guffroy, A., Mourot-Cottet, R., Gérard, L. et al. Neutropenia in Patients with Common Variable Immunodeficiency: a Rare Event Associated with Severe Outcome. J Clin Immunol 37, 715–726 (2017). https://doi.org/10.1007/s10875-017-0434-2

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Keywords

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