Infants Presenting With Recurrent Infections and Low Immunoglobulins: Characteristics and Analysis of Normalization
Authors: Bonilla Francisco A. 
Published: November 2007

Whelan MA, Hwan WH, Beausoleil J, Hauck WW, McGeady SJ. J Clin Immunol. 2006;26:7–11
PURPOSE OF THE STUDY. To determine the outcomes of infants and young children with recurrent infections found to have low levels of ≥1 immunoglobulin (Ig) class (IgG, IgA, or IgM) without other screening laboratory indicators of immunodeficiency.
STUDY POPULATION. Forty-nine infants who presented for evaluation at &lt;24 months of age and had IgG, IgA, or IgM levels of &lt;2 SD below the age-adjusted mean, intact antibody response to tetanus and diphtheria, intact cellular immunity, and no other immunodeficiency diagnoses.
METHODS. Retrospective review of medical charts at a single institution from 1977 to 2005.
RESULTS. Boys accounted for 70% of the patients. Recurrent otitis media was the predominant presentation (78%). Significant associated features were recurrent wheezing with infection (61%) and atopy (27%). Multiple isotypes were reduced in 65% of the patients; low IgA was most prevalent (96%). Only half of the patients had achieved normalization of Ig levels at the end of the observation period. Of these, 84% had become normal by 5 years of age. Of the patients who had not yet normalized at the end of the study, 54% were &gt;5 years old. Two met criteria for selective IgA deficiency. Higher levels of Igs at presentation were associated with shorter times to normalization. Boys who presented at younger ages normalized more quickly than those who presented later. The opposite was true for girls. On average, the time to normalization for girls was 10-fold longer than the time for boys. Serious infections or death were not observed.
CONCLUSIONS. Most patients with this phenotype are boys with recurrent otitis media, wheezing episodes, and atopy. Girls with this presentation may be at greater risk for prolonged immunodeficiency. A “definitive” diagnosis of transient hypogammaglobulinemia can only be conferred retrospectively (ie, after Ig levels have normalized).
REVIEWER COMMENTS. There were several interesting new observations in this group of patients. In particular, the gender differences in time to normalization stand out; the immunologic significance of this finding is not known. The authors correctly pointed out that patients must be followed at least until clinical resolution, if not actual normalization, of Ig values. Only half of the patients normalized during the observation period. It is possible that other specific immunodeficiency diagnoses may be conferred on some of the patients who are still hypogammaglobulinemic. The authors did not comment on whether some patients who initially presented in this way subsequently developed additional clinical and/or laboratory features leading to the diagnosis of other immunodeficiencies. Without knowing this, it is impossible to estimate the predictive value of intact vaccine responses in this setting (ie, how often do we “miss” a different specific immunodeficiency diagnosis if we stop after this initial evaluation). However, these and other reports suggest that the majority of these patients follow a relatively benign course.