Flow Cytometry in the Diagnosis and Follow Up of Human Primary Immunodeficiencies

Primary immunodeficiencies (PID) comprise a group of more than 300 mostly monogenetic disorders of the immune system leading to infection susceptibility and a variety of associated clinical and immunological complications. In a majority of these disorders the absence, disproportions or dysfunction of leucocyte subpopulations or of proteins expressed by these cells are observed. These distinctive features are studied by multicolour flow cytometry and the results are used for diagnosis, follow up, classification and therapy monitoring in patients with PIDs. Although a definite diagnosis almost always relies on genetic analysis in PIDs, the results of flow cytometric diagnostics are pivotal in the initial diagnostic assessment of suspected PID patients and often guide the treating physician to a more selective and efficient genetic diagnostic procedure, even in the era of next generation sequencing technology. Furthermore, phenotypic and functional flow cytometry tests allow to validate novel genetic variants and the mapping of complex disturbances of the immune system in individual patients in a personalized manner. In this review we give an overview on phenotypic, functional as well as disease/protein specific flow cytometric assays in the diagnosis of PID and highlight diagnostic strategies and specialties for several selected PIDs by way of example.