Application of Cytometry in Primary Immunodeficiencies

The field of primary immunodeficiencies (PIDs) is rapidly evolving, especially because of the introduction and routine availability of Next Generation Sequencing (NGS), which is based on targeted panel sequencing or Whole Exome Sequencing (WES) with or without a filter for PID genes. These recent technological advances are significantly impacting PID diagnostics since they improve the identification of variants of known PID genes and also broaden the clinical spectrum of these genes. While NGS methods such as WES allow for the identification of mutations in new candidate genes, their turn-around time is relatively long (i.e. a couple of months in a routine diagnostic setting). In contrast, flow cytometry provides descriptive insight into the composition of leukocyte subsets within a day. With the new generation of clinical cytometers (fast, digital, three laser instruments) it is possible to immunophenotype several dozens of immune cell subsets (naïve and effector subsets, activated subsets of lymphocytes, subsets of innate cells etc) in a short period of time. Flow cytometry can also serve as technology for functional validation of genetic variants’ impact on the immune system. Cytometry also offers an opportunity to measure various immune cell functions concomitantly at a single cell level. Finally, flow cytometry immunophenotyping is crucial for correct interpretation of NGS-based results. Altogether, the application of cytometry in primary immunodeficiencies has a superior position in the diagnosis of severe PIDs (e.g. Severe Combined Immunodeficiency) as it is useful for the classification of disease subgroups in Common Variable Immunodeficiency and is thus, a topic of broad interest for clinicians and laboratory specialists responsible for making fast and accurate diagnosis as well as for researchers in the field of immunology and immunodeficiency. With recent advances in cytometry methods there is an increasing need for development and standardization of complex data analysis at the single cell level as well as analyses of large patient cohorts.

This Research Topic aims to create a bridge across multiple sub-topics with a common interest in:

• Using cytometry to diagnose primary immunodeficiencies.
• Using cytometry to describe immunophenotype of immune cells in PIDs.
• Developing novel cytometry methods enabling the investigation of immune cell function in PIDs.
• Standardizing cytometry methods and data analysis for large cohort of PID patients.
• Highlighting the use of computational methods in cytometry data analysis of PIDs patients.

We welcome the submission of Original Research articles, Reviews, Methods, Protocols and Case Reports on the application of cytometry in the study of immune cells in PIDs.

We acknowledge the initiation and support of this Research Topic by the International Union of Immunological Societies (IUIS). We hereby state publicly that the IUIS has had no editorial input in articles included in this Research Topic, thus ensuring that all aspects of this Research Topic are evaluated objectively, unbiased by any specific policy or opinion of the IUIS.