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ARCHIVES OF HELLENIC MEDICINE: ISSN 11-05-3992
CONTINUING MEDICAL EDUCATION
ARCHIVES OF HELLENIC MEDICINE 2008, 25(4):548-549
ΣΥΝΕΧΙΖΟΜΕΝΗ ΙΑΤΡΙΚΗ ΕΚΠΑΙΔΕΥΣΗ ÁÑ×ÅÉÁ ÅËËÇÍÉÊÇÓ ÉÁÔÑÉÊÇÓ 2008, 25(4):548-549
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G. Loules,
Clinical Immunology Quiz – Case 5 F. Kalala,
A. Mamara,
E. Tsitsami,
Peripheral blood from a 10-year old female was referred M. Speletas
to the Immunology Lab for immunophenotyping. The patient
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complained for recurrent upper respiratory tract infections and Department of Immunology and
Histocompatibility, Medical School,
otitis media during the last year while a history of frequent
University of Thessaly, Larissa, Greece
infections was recorded since infancy. Although, the absolute
number of lymphocyte subsets was into normal ranges (fig. 1 and
tab. 1), the patient displayed a mild hypogammaglobulinemia
(tab. 1). Although the patient did not fulfill the diagnostic criteria
a molecular analysis of TNFRSF13B gene (encoding TACI) was
for the diagnosis of common variable immunodeficiency (CVID),
performed.
Interestingly, the patient was double heterozygous in
TNFRSF13B, carrying the mutations V220A and P251L (fig. 2).
Further analysis demonstrated that her parents were TNFRSF13B
heterozygotes but did not display hypogammaglobulinemia.
Comment
TACI (Transmembrane Activator, calcium modulator and
Cyclophilin ligand Interactor) is a transmembrane receptor, which
mediates isotype switching in B cells. Recently, 6 mutations (in
homozygous or heterozygous state) in TNFRSF13B gene were
found to be present in 10% to 20% of patients with CVID, implying
the contribution of this gene in the disease pathogenesis and/or
phenotype. However, TNFRSF13B mutations were reported in normal
Figure 1. Flow cytometry analysis showing normal lymphocyte
subsets.
Table 1. Lymphocyte subsets and serum immunoglobulins of the
patient.
Blood lymphocyte subpopulations (×109/L)
Total lymphocyte count 4.217 (2.9–5.1)
T lymphocytes
CD3 3.163 (1.8–3.2)
CD4 1.718 (1.0–1.8)
CD8 1.242 (0.3–0.6)
B lymphocytes
CD19 0.577 (0.3–0.6)
Quantitative serum immunoglobulins (mg/dL)
IgG 919 (934–1640)
IgA 51 (85–242)
Figure 2. Molecular analysis of TNFRSF13B gene, showing the presence
IgM 47 (100–252)
of the V220A and P251L mutations.
Clinical Immunology Quiz – Case 5 549
individuals, indicating possibly that when alone do not necessarily Corresponding author:
predispose to CVID pathogenesis. Nevertheless, their presence could
M. Speletas, Department of Immunology and Histocompati-
be considered as an early indicator of CVID emergence, considering bility, Medical School, University of Thessaly, University Hospi-
that in several CVID patients the diagnosis is underestimated and a tal of Larissa, GR-411 10 Larissa, Greece, Tel: +302410681862,
delayed diagnosis can lead to increased morbidity and mortality. Thus, Fax: +302410682580,
in our patient, persistent hypogammaglobulinemia and recurrent e-mail: maspel@med.uth.gr
infections are followed-up for Ig replacement to be considered.
Diagnosis: TACI mutations in a child with hypogammaglobulinemia
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