Table 4.
Flow cytometry-based diagnosis of IEIs.
| IEI | Associated flow cytometry findings |
|---|---|
| Robust evidence | |
| SCID | T-cell count <300/μl |
| Omenn Syndrome | Absent or severely decreased naïve T cells and RTE |
| MHC-II deficiency | Absent or markedly decreased HLA-DR expression on B cells |
| WAS | Absent or markedly decreased WASp expression on T cells |
| XLA | Absent or very low (<2%) circulation B cells with absent/reduced Btk expression on monocytes |
| XL-CGD | Absent NADPH oxidase activity |
| FHL type 2 | Absent or markedly decreased perforin expression on NK cells |
| FHL types 3, 4 and 5 | Defective resting NK-cell degranulation assay |
| LAD-1 | Absent CD18/CD11a expression on neutrophiles |
| AR-CD46 deficiency | Absent CD46 expression on T cells |
| CHAPLE disease | Absent CD55 expression on neutrophiles |
| Suggestive evidence | |
| CD3γ deficiency | Low CD3/TCRαβ expression on T cells |
| HIES | Markedly decreased Th17 cells or defective IL-17 production associated or not with STAT3 phosphorylation defect |
| CMC-STAT1 GOF | Markedly decreased Th17 cells or defective IL-17 production associated with hyperphosphorylation of STAT1 |
| APDS | Expanded transitional B cells with reduced switched memory B cells and decreased naïve T cells |
| ALPS-FAS | Significant increase in TCRαβ DNT (>7% of CD3+ T cells) |
| IPEX syndrome | Absent or markedly decreased FOXP3+CD25+ Treg |
| AR-CGD | Reduced NADPH oxidase activity |
| AD-CD46 deficiency | ~ 50% reduction of CD46 expression on lymphocytes |
| Informative clues | |
| Hypomorphic V(D)J recombination defects | Markedly decreased naïve T cells and RTE associated or not with reduced B cells |
| DiGeorge syndrome | Reduced naive T cells and RTE |
| Ataxia Telangiectasia | CD3 lymphopenia with reduced naive T cells |
| CVID | Markedly decreased switched memory B cells |
| LRBA deficiency | Reduced switched memory B cells with expanded CD21lo B cells |
| RIPK1 deficiency | Decreased central and effector memory CD4 T cells Decreased switched and non-switched memory B cells Raised transitional B cells |
| Good’s syndrome | Absent or markedly decreased B cells Low CD4/CD8 ratio |
AD, autosomal dominant; ALPS, autoimmune lymphoproliferative syndrome; APDS, activated PI3K delta syndrome; AR, autosomal recessive; CGD, chronic granulomatous disease; CHAPLE, complement hyperactivation angiopathic thrombosis and protein-losing enteropathy; CMC, chronic mucocutaneous candidiasis; CVID, common variable immunodeficiency; FHL, familial hemophagocytic lymphohistiocytosis; HIES, hyper-IgE syndrome; IPEX, immune dysregulation-polyendocrinopathy-enteropathy-x-linked; LRBA, LPS-responsive beige-like anchor protein; LAD, leukocyte adhesion deficiency; LRBA, LPS-responsive beige-like anchor protein; MHC, major histocompatibility complex; RIPK1, receptor-interacting serine/threonine-protein kinase 1; SCID, severe combined immunodeficiency; STAT, signal transducer and activator of transcription; WAS, Wiskott Aldrich syndrome; XLA, X-linked agammaglobulinemia.