Establishment of pediatric reference ranges for circulating naïve and memory T and B cell subsets guided by the human...

Our knowledge of the immune system continues to expand at a rapid pace, and this coupled with technological advances now enables us to interrogate both the breadth and the depth of the immune response at levels without precedent. This has also facilitated rapidly integrating some of this carefully vetted knowledge into clinical practice. Notable examples of these advances include successfully harnessing the therapeutic potential of the immune system (immunotherapy), as well as an expanding menu of clinical flow-cytometry laboratory tests to assess the phenotype and function of the cellular immune response. This has also given rise to an emerging sub-discipline called "Immune-Health", with its premise undergirded by the notion that the surveillance capacity and sentinel nature of the immune response might enable the immune system to serve as a reliable barometer of overall health of the individual. At its core, immune-health entails defining baseline immune characteristics for each individual so that perturbations in this baseline signature can serve as clinically actionable biomarkers that might predict the onset, help monitor the progression and potentially mitigate the effects of the underlying disease process. Defining appropriate reference-ranges (RR) for key cellular immune parameters constitutes one of the essential building-blocks of the concept of immune-health. Establishing pediatric RR for cellular correlates of immune-health and disease is a time-consuming and labor-intensive process, and consequently only a select few specialty laboratories at some children's hospitals (with a well-established immunodeficiency/immunedysregulation clinical service) and a couple of large national reference laboratories in the United States (US) have invested their time and effort into this endeavor. Furthermore, the lack of standardization in the definition of immune subsets has also complicated this effort. In 2012, the Human Immunophenotyping Consortium (HIPC) established by the National Institute of Allergy and Infectious Diseases (NIAID)-Division of Allergy, Immunology and Transplantation, published a benchmark study that attempted to standardize the definitions for several cellular immune parameters. In general, Europe has led the charge in advancing these standardization efforts, while similar efforts in the US have been rather sparse, and currently there's a marked paucity of US based studies describing the establishment of pediatric reference ranges (RR) for T and B cell subsets based on the HIPC standardization initiative. In this report, we describe the results of the endeavor, at a large, free-standing children's hospital in the US with a busy clinical immunology service, to establish pediatric reference ranges for naïve and memory T and B cell subsets largely adapted from the subset definitions outlined by the HIPC.