The PedPAD study: boys predominate in the hypogammaglobulinaemia registry of the ESID online database

Abstract

SummaryHypogammaglobulinaemias are the most common primary immunodeficiency diseases. This group of diseases is very heterogeneous, and little is known about these diseases in children. In the Pediatric Predominantly Antibody Deficiencies (PedPAD) study, we analysed data from the European Society for Immunodeficiencies (ESID) online database to gain more insight into the characteristics of children with hypogammaglobulinaemia; 46 centres in 18 different countries agreed to participate. Data from 2076 of the 3191 children who were registered at the time of data extraction with a diagnosis of hypogammaglobulinaemia (this excludes agammaglobulinaemia and defects in class-switch recombination) were available for analysis. The data set showed several limitations. Because of country-related differences in diagnostic criteria used for the classification of different types of primary hypogammaglobulinaemia, further analysis of the data was performed in the combined data set. The most striking observation is the strong majority of male patients in the group of children with primary hypogammaglobulinaemia (n = 1292, 63%). This male predominance was observed in each of the 18 countries involved. The boys were younger at diagnosis (mean age males 5·3 years; mean age females 5·8 years). Moreover, one or more complications were more frequently reported in boys (12%) compared to girls (5%). The male predominance suggests that patients with an undetected or unknown X-linked genetic cause are included in this group of children registered as primary hypogammaglobulinaemia.

Hypogammaglobulinemia in children: a warning sign to look deeply?

“…The clinical presentation in this series was similar to those reported in other publications . Impaired differentiation of B lymphocytes into memory cells is the main cellular defect reported in CVID, and in an attempt to classify CVID population, the determination of the frequency of switched memory B cells is currently used in patients older than 4 years .…”

“…Hypogammaglobulinemia and recurrent bacterial infections are the classical manifestations of CVID . However, in children, these symptoms can also result of immaturity of the immune system, THI, UH, or other well‐defined PID disease . Identification of pathological cases is essential to implement appropriate therapy and avoid severe complications and morbi‐mortality .…”

“…Diagnosis of CVID in childhood represents a challenge due to the lack of specific markers in an immature immune system and over 90% without a defined genetic defect . Predominance in male gender, positive family history of PID unrelated to consanguinity, and a greater potential for a poorer prognosis have been described in pediatric CVID .…”

“…Diagnosis of CVID in childhood represents a challenge due to the lack of specific markers in an immature immune system and over 90% without a defined genetic defect . Predominance in male gender, positive family history of PID unrelated to consanguinity, and a greater potential for a poorer prognosis have been described in pediatric CVID . Cellular disturbances include low B‐cell counts, decreased percentages of switched (CD19 + CD27 + IgD − ) and non‐switched memory B cells (CD19 + CD27 − IgD + ), and increased number of memory CD4 + T cells (CD4 + CD45RA − ) and low number of total and naive CD4 + T cells (CD4 + CD45RA + ), depending on the age and severity of clinical features .…”

B lymphocyte subsets and outcomes in patients with an initial diagnosis of transient hypogammaglobulinemia of infancy

“…It is also defined as a prolongation of physiological hypogammaglobulinemia during infancy without the impairment of specific antibody responses . According to a recent study, THI is one of the most common immunodeficiency diagnoses, affecting 24% of children with hypogammaglobulinemia . THI is considered a transient immunodeficiency, in which the immunoglobulin deficiency generally recovers when the patient is between 2 and 4 years of age.…”