Impaired specific antibody response and increased B-cell population in transient hypogammaglobulinemia of infancy

Division of Immunology, Children's Hospital Boston, Harvard Medical School, Boston, Massachusetts, USA.
Annals of allergy, asthma & immunology: official publication of the American College of Allergy, Asthma, & Immunology (Impact Factor: 2.75). 12/2006; 97(5):590-5. DOI: 10.1016/S1081-1206(10)61085-X
Source: PubMed

ABSTRACT Transient hypogammaglobulinemia of infancy (THI) is a heterogeneous disorder with poorly understood pathophysiology.
To better characterize THI and improve understanding of its pathophysiology.
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.
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.
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.

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