Infants Presenting with Recurrent Infections and Low Immunoglobulins: Characteristics and Analysis of Normalization

Abstract

To better characterize infants presenting with diminished immunoglobulin levels and intact antibody formation, we present 49 such infants, correlating presenting characteristics with history and time to immunoglobulin normalization. Term infants with the following characteristics were included: 1) one or more immunoglobulin classes > 2SD below mean, 2) protective antibody titer to tetanus and diphtheria, 3) intact cellular immunity, 4) no features of other syndromes. The children were 69.4% male and had recurrent otitis media (77.6%), wheezing (61.2%), and atopy (26.5%). Diminished IgA (95.9%) was most common, but 65.3% had multiple isotypes diminished. During follow-up, 25/49 (51%) normalized immunoglobulins, of whom 80% were male; only 48% normalized in infancy. Female immunoglobulin normalization was significantly delayed (p< .001). No deaths or serious infections occurred. This phenotype is predominantly seen in male infants with otitis media and wheezing. Female infants have significantly delayed immunoglobulin normalization. Transient hypogammaglobulinemia of infancy can be diagnosed only retrospectively.

Phenotypic Parameters Predict Time to Normalization in Infants with Hypogammaglobulinemia

“…In agreement with previously reported findings, [8] male infants resolved more quickly than females (p=0.001). The median time to resolution in males was 13 months with 73% resolving in 3 years.…”

“…[7] At the time of initial recognition of hypogammaglobulinemia in an infant, since this may be physiologic, immunologists are often finding with clinically relevant questions regarding the likely duration of hypogammaglobulinemia. Previous studies have shown that males are more likely than females to have resolution of hypogammaglobulinemia during infancy, [8] however, other than this observation, there has been little information that would allow an informed prediction about the probable time to resolution to hypogammaglobulinemia. The goal of this study was to define parameters, present at the time of diagnosis that might predict time to resolution of hypogammaglobulinemia.…”

“…Prior studies checked the reasonableness of this model by Kaplan-Meier curves, using interval midpoints as time to normalization, and found very similar results when compared to model-based graphs. [8] Quartiles were compared with one another regarding age at diagnosis and percentage male using Kruskal-Wallis and Chi-square methods, respectively.…”

Five years of experience in transient hypogammaglobulinemia of infancy

“…Whealan ve ark. (21) hipogamaglobülinemi tanısı ile izlenen 49 olgunun tamamı-nın difteri ve tetanos aşı yanıtlarının olduğu bildirmiş-tir. Mammedova ve ark.…”

Prototypic Three Pediatric Cases of Recurrent Wheezing Attacks Associated with Hypogammaglobulinemia

“…Recurrent wheezing resistant to β2 adrenergic-agonist and anti-cholinergic therapies are usually investigated for hypogammaglobulinemia. In fact, recurrent viral infections including lower respiratory tract infections have been reported as associated to transient hypogammaglobulinemia of infancy (THI) [1][2][3][4][5]. Yet, the main clinical feature in patients affected by infantile hypogammaglobulinemia remains recurrent infections.…”