Neutropenia in Patients with Common Variable Immunodeficiency: a Rare Event Associated with Severe Outcome
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Common variable immunodeficiency (CVID) is characterized by infections and hypogammaglobulinemia. Neutropenia is rare during CVID.
The French DEFI study enrolled patients with primary hypogammaglobulinemia. Patients with CVID and neutropenia were retrospectively analyzed.
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.
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.
KeywordsNeutropenia Autoimmune cytopenia Common variable immunodeficiency (CVID) Next genome sequencing
Autoimmune hemolytic anemia
Common variable immuno-deficiency
Ears, nose, and throat
Granulocyte aggregation test
Granulocyte immunofluorescence test
Human neutrophil antigen
Idiopathic thrombocytopenic purpura
Late-onset combined immunodeficiency
Monoclonal antibody immobilization of granulocyte antigen
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.
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.
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