Jennifer A. Sutter

Adrenocortical tumors are rare in children and are associated with a poor prognosis when malignant. The fund of knowledge regarding etiology, presentation and clinical outcomes remains limited. Evaluation of genetic disorders associated with the development of adrenocortical disorders has allowed researchers to identify a number of mutations that may be involved in tumorigenesis, including alterations in the GNAS1, PRKAR1A, TP53 and IGF2 genes. Clinical presentation in children is associated most commonly with young age, female gender and symptoms of virilization. Most children have localized disease at presentation which may be associated with a better prognosis when compared to adults. Surgical resection remains the only potentially curative treatment and mitotane, the most frequently used chemotherapeutic agent, has a poor response rate and is highly toxic. Broader participation in multi-center research, such as the International Pediatric Adrenocortical Tumor Registry, is needed to collect sufficient data to better guide our clinical management.

Although autoantibodies have been used for decades as diagnostic and prognostic markers in type 1 diabetes (T1D), further analysis of developmental abnormalities in B cells could reveal tolerance checkpoint defects that could improve individualized therapy. To evaluate B cell developmental progression in T1D, immunophenotyping was used to classify circulating B cells into transitional, mature naïve, mature activated, and resting memory subsets. Then each subset was analyzed for the expression of additional maturation-associated markers. While the frequencies of B cell subsets did not differ significantly between patients and controls, some T1D subjects exhibited reduced proportions of B cells that expressed transmembrane activator and CAML interactor (TACI) and Fas receptor (FasR). Furthermore, some T1D subjects had B cell subsets with lower frequencies of class switching. These results suggest circulating B cells exhibit variable maturation phenotypes in T1D. These phenotypic variations may correlate with differences in B cell selection in individual T1D patients.

There are few studies of the developmental changes in B-cell subsets in children. Recent data from adult populations demonstrate that alterations to B-cell subsets have functional consequences and can be helpful diagnostically. Comparable studies in children have been hindered by the lack of normative data and by significant changes with age. This study evaluated B-cell subsets by 4-color flow cytometry in 47 children of different ages. The use of a 4-color platform is compatible with broad use in clinical laboratories. We found that there are rapid changes in the B-cell compartment in infancy and early childhood. Total B-cell numbers decline early in life, and this correlates with a decline in transitional B cells and naïve B cells. The decline is most rapid between 1 and 5 years of age, with a slower decline later in childhood. In contrast, nonswitched and switched memory B cells both increase during the 1st 5 years of life. The decline in B-cell numbers did not occur until after 1 year of age, suggesting that the period after birth is a unique developmental window. These data provide a reference set for further studies on B-cell dysfunction in pediatric disorders. The changes occurring in early childhood document the need for age-related assessments and serve to underscore the B-cell-specific kinetics of immunologic development in humans.