Flow cytometry-based diagnosis of primary immunodeficiency diseases

Abstract

Primary immunodeficiencies (PIDs) are a heterogeneous group of inherited diseases of the immune system. The definite diagnosis of PID is ascertained by genetic analysis; however, this takes time and is costly. Flow cytometry provides a rapid and highly sensitive tool for diagnosis of PIDs. Flow cytometry can evaluate specific cell populations and subpopulations, cell surface, intracellular and intranuclear proteins, biologic effects associated with specific immune defects, and certain functional immune characteristics, each being useful for the diagnosis and evaluation of PIDs. Flow cytometry effectively identifies major forms of PIDs, including severe combined immunodeficiency, X-linked agammaglobulinemia, hyper IgM syndromes, Wiskott-Aldrich syndrome, X-linked lymphoproliferative syndrome, familial hemophagocytic lymphohistiocytosis, autoimmune lymphoproliferative syndrome, IPEX syndrome, CTLA 4 haploinsufficiency and LRBA deficiency, IRAK4 and MyD88 deficiencies, Mendelian susceptibility to mycobacterial disease, chronic mucocuneous candidiasis, and chronic granulomatous disease. While genetic analysis is the definitive approach to establish specific diagnoses of PIDs, flow cytometry provides a tool to effectively evaluate patients with PIDs at relatively low cost.

Expanding TREC and KREC Utility in Primary Immunodeficiency Diseases Diagnosis

“…PID is a large group of disorders encompassing more than 400 conditions affecting development and/or functioning of the immune system (23). Flow cytometry is a sensitive and important tool in evaluating the immune system function and in PID diagnosis (24). However, it is expensive, not easily available in developing countries and requires appropriate training and equipment.…”

Primary Immunodeficiency

“…As our understanding of the defect or dysfunction of immune system increases, immunophenotypic and functional assays based on flow cytometry have been extensively used in identifying the abnormality of various cell types and their functions associated with certain diseases, including PIDs. Furthermore, flow cytometry is also a favorable technique for the measurement of intra-and extracellular cytokine production (e.g., IL12, IFN, TNF, and TH17), cell surface protein expression (e.g., Foxp3, CTLA-4, and BTK), and cellular signaling pathways (e.g., phosphor-STAT) [45]. The information gained from flow cytometry analysis can assist not only in the diagnosis, monitoring, and treatment of the diseases but also in understanding the influence of immune system associated with genetic defects that are newly identified.…”

“…Additionally, seeking for a consistent healthy Table 5. Phenotypic and functional assessment for PIDs by flow cytometry [45,46]. Primary Immunodeficiency DOI: http://dx.doi.org /10.5772/intechopen.89624 fresh blood as assay normal control and obtaining a proper reference range can be challenging in routine laboratory practice.…”

Inflammatory bowel diseases and primary immunodeficiency diseases

“…Pathway genes in IBD-associated loci Epithelial barrier function and repair CDH1, ERRFI1, GNA12, HNF4A, ITLN1, MUC19, NKX2-3, PLA2G2E, PTGER4, REL, STAT3 Innate mucosal defence CARD9, FCGR2A, IL18RAP, ITLN1, NOD2, REL, SLC11A1 Autophagy ATG16L1, CUL2, DAP, IRGM, LRRK2, NOD2, PARK7 Apoptosis/necroptosis DAP, FASLG, MST1, PUS10, THADA Activation of adaptive immune response IL23R response pathway CCR6, IL12B, IL21, IL23R, JAK2, STAT3, STAT4, TYK2 NF-jB NFKB1, REL, TNFAIP3, TNIP1 Aminopeptidases ERAP1, ERAP2 IL-2 and IL-21 T-cell activation IL2, IL21, IL2RA Regulation of adaptive immune response TH17 cell differentiation AHR, CCR6, IL2, IL21, IL23R, IRF4, JAK2, RORC, STAT3, TNFSF15, TYK2 T-cell activation ICOSLG, IFNG, IL12B, IL2, IL21, IL23R, IL2RA, IL7R, NDFIP1, PIM3, PRDM1, TAGAP, TNFRSF9, TNFSF8 B-cell [16,17]. XIAP expression is decreased in lymphocytes and monocytes of some patients with XIAP deficiency (Figure 4(a)) [17,18], and muramyl dipeptide signaling is selectively defective in patients with XIAP deficiency (Figure 4(b)) [19]. IL-10 receptor deficiency can also be detected using assays that determine whether exogenous IL-10 suppresses lipopolysaccharide-induced cytokine production in peripheral blood mononuclear cells [20,21].…”