Transient hypogammaglobulinemia and unclassified hypogammaglobulinemia: ‘Similarities and differences’

Abstract

Transient hypogammaglobulinemia of infancy (THI) is characterized by recurrent infections and one or more reduced serum immunoglobulin (Ig) levels. Usually, this clinical picture resolves spontaneously by 3 yr of age. However, hypogammaglobulinemia persists until adolescence in some patients. In recent years, those patients have been classified as undefined/unclassified hypogammaglobulinemia (UCH). We aimed to evaluate the clinical and immunologic features of patients with THI and UCH considering age of recovery and to assess relationships between hypogammaglobulinemia, infections, and allergic manifestations. We reviewed the medical records of children followed with a diagnosis of hypogammaglobulinemia from 2001 to 2007. Patients with decreased levels (<2 s.d.) of one or more major Ig isotypes (IgG, IgA, IgM) with normal antibody responses and lymphocyte subpopulations were included (n = 374). Those patients whose Igs normalized during the follow-up period were classified as THI and the others as UCH. The THI group consisted of 71 patients (27 females, 44 males) with a mean recovery age of 68.87 +/- 36.5 months. About 95% of patients with THI recovered before 10 yr of age. The UCH group consisted of 303 patients (105 females, 198 males) with a mean age at diagnosis of 52 +/- 42 months. The most common presenting manifestations in the THI and UCH groups were upper respiratory tract infections (URTIs), lower respiratory tract infections, and asthma (42%, 50%, and 52% in the THI group vs. 39%, 53%, and 55% in the UCH group, respectively). In the THI group, the prevalence of atopic disease was related to age and found to be increased markedly after 44 months. In all patients, the prevalence of asthma was independently and positively associated with family history of atopy and age, whereas it was negatively associated with recurrent URTIs. Patients with THI and UCH have similar clinical and immunologic features. The normalization of Igs may be delayed in a majority of the patients with hypogammaglobulinemia. This observation may be a contribution to the classical definition and diagnostic criteria for THI.

Microbes, Immunity, and Behavior: Psychoneuroimmunology Meets the Microbiome

“…Neonates have low expression of co-stimulatory molecules, diminished dendritic cell (DC) differentiation, impaired phagocytosis as well as defective interaction between DCs, T lymphocytes and regulatory T cells and impaired cytotoxic activity of T cells (Kotiranta-Ainamo et al, 2004;Velilla et al, 2006). Furthermore, the activity of the transplacentally derived maternal immunoglobulin G antibodies results in a deficiency of specific humoral responses, which include minimal levels of IgA in neonates (Keles et al, 2010). Similar findings have been reported in animal studies.…”

Gut Microbiota: The Conductor in the Orchestra of Immune–Neuroendocrine Communication

“…31,32 Moreover, the suppressive activity of the transplacentally transmitted maternal IgG antibodies contributes to the deficiency of specific humoral response, including the low production of IgA in human neonates. 33 Immune immaturities have also been reported in animal studies, in which germ-free (GF) mice and those in the first days of colonization share many traits, characterized by smaller Peyer's patches and reduced cellularity of the lamina propria with lower Cd4 þ and Cd8 þ T cells. 34,35 Plasma cells and intraepithelial lymphocytes are rare in the small intestinal mucosa, and sIgA levels are significantly lower with reduced expression of genes and activation markers of intestinal macrophages.…”

Evolution of Hypogammaglobulinemia in Premature and Full-Term Infants

“…The immunological profile of this child was evaluated to assess the history of recurrent infections: he has no allergic diseases, his lymphocyte subpopulations are normal, whereas he presents a concomitant IgG1 and IgG2 deficit, not clinically significant. This subject cannot fall within the current criteria for THI (3,10); he shows a benign clinical course with later normalization of his IgG, as had occurred in other cases described by the literature (11)(12)(13)(14).…”