Impaired specific antibody response and increased B-cell population in transient hypogammaglobulinemia of infancy.
BACKGROUND
Transient hypogammaglobulinemia of infancy (THI) is a heterogeneous disorder with poorly understood pathophysiology.


OBJECTIVE
To better characterize THI and improve understanding of its pathophysiology.


METHODS
Twenty-four children with hypogammaglobulinemia defined by an IgG level less than 2 SDs below the mean on 2 occasions, who did not have other immunologic diagnoses, were followed and retrospectively reviewed.


RESULTS
The average z-score for IgG level at presentation was -2.4 (mean age, 12 months; median age, 8 months), with a mean level of 254 mg/dL. Thirteen of 24 patients had IgA levels less than 2 SDs below the mean, 5 had IgM levels less than 2 SDs below the mean, and 7 of 23 had elevated IgE levels. Eighteen were followed up until their IgG levels normalized (mean age, 27 months; median age, 23 months), with 12 of 18 normalizing by 24 months and the remainder by 59 months. There was a significant association between presenting IgG z-score and duration of disease (P = .05). Five of the 18 patients had absolute CD19+ B-cell counts greater than the 95% percentile for age (P < .001), and the mean percentage and absolute CD19+ B-cell count across all patients were greater than those of the age-matched controls (P = .02). Most patients had nonprotective titers to Haemophilus influenzae type b vaccine, and one third had nonprotective titers to tetanus vaccine. Twenty patients carried at least one atopic diagnosis, and 13 of those had recurrent wheezing.


CONCLUSIONS
THI is associated with a number of immunologic abnormalities beyond just hypogammaglobulinemia. These abnormalities include impaired specific antibody responses and increased proportions of CD19+ B cells and may be suggestive of particular immunologic mechanisms that result in hypogammaglobulinemia.
Dorsey
Morna J
MJ
Division of Immunology, Children's Hospital Boston, Harvard Medical School, Boston, Massachusetts, USA. MDorsey@hsc.usf.edu
Orange
Jordan S
JS
D000361:Agammaglobulinemia / Q000097:blood / Q000276:immunology*; D000917:Antibody Formation / Q000276:immunology*; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology*; D002675:Child, Preschool; D006801:Humans; D007111:Immunity, Cellular / Q000276:immunology; D007136:Immunoglobulins / Q000097:blood; D007223:Infant; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology
D007136:Immunoglobulins