Late-onset combined immune deficiency: a subset of common variable immunodeficiency with severe T cell defect.
BACKGROUND
Common variable immunodeficiency (CVID) is a primary immune deficiency defined by defective antibody production. In most series, a small proportion of patients present with opportunistic infections (OIs).


METHODS
The French DEFI study has enrolled patients with primary hypogammaglobulinemia and allows a detailed clinical and immunologic description of patients with previous OIs and/or at risk for OIs.


RESULTS
Among 313 patients with CVID, 28 patients (8.9%) presented with late-onset combined immune deficiency (LOCID), defined by the occurrence of an OI and/or a CD4(+) T cell count <200 x 10(6) cells/L, and were compared with the remaining 285 patients with CVID. The patients with LOCID more frequently belonged to consanguineous families (29% vs 8%; P = .004). They differed from patients with CVID with a higher prevalence of splenomegaly (64% vs 31%), granuloma (43% vs 10%), gastrointestinal disease (75% vs 42%), and lymphoma (29% vs 4%). Even on immunoglobulin substitution, they required more frequent antibiotics administration and hospitalization. Lymphocyte counts were lower, with a marked decrease in CD4(+) T cell counts (158 x 10(6) vs 604 x 10(6) cells/L; P < .001) and a severe defect in naive CD45RA(+)CCR7(+)CD4(+) T cell counts (<20% of total CD4(+) T cells in 71% of patients with LOCID vs 37% of patients with CVID; P = .001). The CD19(+) B cell compartment was also significantly decreased (20 x 10(6) vs 102 x 10(6) cells/L; P < .001).


CONCLUSIONS
LOCID differs from classic CVID in its clinical and immunologic characteristics. Systematic T cell phenotype may help to discriminate such patients from those with CVID. Identification of this phenotype should result in a more fitted diagnostic and therapeutic approach of infections and could provide insights for genetic diagnosis.
Malphettes
Marion
M
Département d'Immunologie, Hôpital Saint-Louis, Assistance Publique Hôpitaux de Paris, Paris, France. marion.malphettes@sls.aphp.fr
Gérard
Laurence
L
Carmagnat
Maryvonnick
M
Mouillot
Gaël
G
Vince
Nicolas
N
Boutboul
David
D
Bérezné
Alice
A
Nove-Josserand
Raphaële
R
Lemoing
Vincent
V
Tetu
Laurent
L
Viallard
Jean-François
JF
Bonnotte
Bernard
B
Pavic
Michel
M
Haroche
Julien
J
Larroche
Claire
C
Brouet
Jean-Claude
JC
Fermand
Jean-Paul
JP
Rabian
Claire
C
Fieschi
Claire
C
Oksenhendler
Eric
E
D000328:Adult; D000361:Agammaglobulinemia / Q000276:immunology / Q000473:pathology; D017668:Age of Onset; D000368:Aged; D017074:Common Variable Immunodeficiency / Q000150:complications* / Q000276:immunology*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009894:Opportunistic Infections / Q000209:etiology / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology* / Q000473:pathology*; D055815:Young Adult