Abstract
Inborn errors of immunity (IEI) are a group of inherited heterogeneous disorders affecting
the immune system characterized by increased susceptibility to infections, immune
dysregulation, and lymphoproliferation. Flow cytometry (FCM) is a rapid and reliable
technique for evaluation and enumeration of immune cells. It also helps in understanding
the functional and signaling pathways of the immune system. Lymphocyte subset analysis
is a simple and effective screening tool in suspected combined and humoral immunodeficiency
patients. Qualitative phagocytic defects such as chronic granulomatous disease and
leucocyte adhesion defect are easily diagnosed by FCM. Study of intracellular proteins
(e.g., BTK, WASP, DOCK8), cytokine production, and signaling molecules (e.g., STAT3)
by FCM is very useful but also quite challenging to establish. T and B lymphocyte
interaction for normal class switching of B cells can be assessed and can help in
diagnosis of combined variable immunodeficiency and hyperimmunoglobulin M syndrome.
FCM is also used in posttransplant monitoring of IEI patients and also in prenatal
diagnosis in suspected cases. It is also useful in validation of variants of uncertain
significance obtained in exome sequencing. FCM results should always be interpreted
with clinical history and, if needed, should be confirmed with molecular genetic studies
before establishing the final diagnosis. Ensuring good sample quality and running
parallel controls with patient samples will avoid the preanalytical and analytical
errors. This review describes the applications of FCM in the diagnosis of various
IEI.
Keywords
inborn errors of immunity - flow cytometry - primary immunodeficiency - phagocytic
defects - immune dysregulation - antibody deficiency
