Table 2.
Distribution and laboratory findings of IEIs in our series.
| Category | Disease | N (%) | Age at diagnosis (months) median (range) |
Associated flow cytometry findings | |
|---|---|---|---|---|---|
| Findings | % | ||||
| Combined immunodeficiencies | 163 (24.3%) | 17 (1 – 552) | |||
| SCIDs | 30 (4.5%) | 5 (2 – 17) | T cells < 300/μl | 96.7% | |
| Omenn Syndrome | 8 (1.2%) | 4.5 (1 – 10) | Absent naïve T cells Absent RTE Absent B cells |
100% 100% 100% |
|
| Leaky SCIDs | 9 (1.3%) | 19 (5 – 240) | Decreased naïve T cells Very low RTE Reduced B cells |
100% 100% 88.9% |
|
| MHC-II deficiency | 35 (5.2%) | 20 (1 – 132) | Absent HLA-DR expression on B cells CD4 lymphopenia Inverted CD4/CD8 ratio |
100% 88.6% 74.3% |
|
| Other CID | 81 (49.7%) | 36 (2 – 552) | CD4 lymphopenia Inverted CD4/CD8 ratio Decreased naïve CD8 T cells Decreased naïve CD4 T cells |
74.1% 60.5% 95.8% * 81.9% * |
|
| CIDs with associated or syndromic features | 101 (15.1%) | 48 (1 – 204) | |||
| DiGeorge syndrome | 7 (1.0%) | 3 (2 – 11) | CD3 lymphopenia | 100% | |
| Ataxia Telangiectasia | 11 (1.6%) | 90 (30 – 204) | CD3 lymphopenia Decreased naïve T cells |
100% 100% |
|
| Wiskott-Aldrich syndrome | 16 (2.4%) | 8 (1 – 48) | CD4 lymphopenia Inverted CD4/CD8 ratio Absent/reduced WASp expression |
62.5% 62.5% 66.7% ** |
|
| Hyper-IgE syndrome | 57 (8.5%) | 60 (8 – 192) | Defective IL-17 production Low CXCR3−CCR6+ Th17 cells Absent/reduced STAT3 phosphorylation |
81.8%#
45.5%# 9.1%# |
|
| ARPC1B deficiency | 2 (0.3%) | 96 (72 – 120) | Hyper-IgE CD3 lymphopenia Decreased naïve T cells Expanded TCRαβ DNT |
100% 100% 100% 50% |
|
| Predominantly antibody deficiencies | 155 (23.1%) | 96 (5 – 804) | |||
| Agammaglobulinemia | 17 (2.5%) | 36 (5 – 312) | Severe decrease of sIg Absent/profoundly decreased B cells Absent Btk expression (in male patients) |
100% 100% 100% ¥ |
|
| CVID | 70 (10.4%) | 252 (18 – 804) | Reduced switched memory B cells Expanded transitional B cells Expanded CD21lo B cells |
80.9%
§
23.8% § 28.6% § |
|
| Activated p110δ syndrome | 2 (0.3%) | 21 (18 – 24) | Reduced switched memory B cells Expanded transitional B cells Decreased naïve T cells |
100% 100% 100% |
|
| SIAD | 15 (2.2%) | 72 (30 – 624) | |||
| Unclassified antibody deficiency | 53 (7.9%) | 48 (5 – 708) | |||
| Diseases of immune dysregulation | 49 (7.3%) | 48 (1 – 336) | |||
| Chediak-Higashi Syndrome | 9 (1.3%) | 30 (1 – 84) | Defective NK-cell degranulation assay | 100% £ | |
| Griscelli Syndrome | 1 (0.1%) | 72 | |||
| FHL | 7 (1.0%) | 14 (1 – 54) | Defective/abnormal NK-cell degranulation | 71.4% | |
| ALPS | 5 (0.7%) | 42 (10 – 132) | Increased TCRαβ DNT | 100% | |
| RIPK1 deficiency | 4 (0.6%) | 78 (48 – 144) | Hypo-IgA and hypo-IgM Reduced switched memory B cells Elevated transitional B cells CD4 lymphopenia |
100% 100% 100% 100% |
|
| LRBA deficiency | 3 (0.4%) | 216 (156 – 336) | Hypogammaglobulinemia Reduced switched memory B cells Expanded CD21lo B cells |
100% 100% 100% |
|
| TPP2 deficiency | 2 (0.3%) | 106 (32 – 180) | Hypogammaglobulinemia Reduced naïve T cells |
100% 100% |
|
| IPEX syndrome | 1 (0.1%) | 17 | Markedly decreased FoxP3+CD25+ regulatory T cells | 100% | |
| Congenital defects of phagocyte number or function | 20 (3.0%) | 23 (1 – 372) | |||
| Congenital neutropenia | 8 (1.2%) | 22.5 (3 – 36) | |||
| Cyclic neutropenia | 2 (0.3%) | 26.5 (23 – 30) | |||
| CGD | 7 (1.0%) | 36 (5 – 372) | Absent/markedly reduced NADPH oxidase activity | 100% | |
| LAD-1 | 2 (0.3%) | 9.5 (1 – 18) | Absent CD18/CD11a expression | 100% | |
| Defects in intrinsic and innate immunity | 12 (1.8%) | 66 (18 – 252) | |||
| MSMD | 4 (0.6%) | 78 (30 – 252) | |||
| CMC | 5 (0.7%) | 36 (24 – 72) | IL-17A production defect Hyperphosphorylation of STAT1 after IFN-γ stimulation | 100% 100% |
|
| Autoinflammatory disorders | 2 (0.3%) | 84 (72 – 96) | |||
| Blau syndrome | 1 (0.1%) | 72 | |||
| A20 deficiency | 1 (0.1%) | 96 | |||
| Complement deficiencies | 153 (22.8%) | 288 (12 – 972) | |||
| C1 inhibitor deficiency | 115 (17.2%) | 336 (12 – 972) | |||
| Factor I deficiency | 5 (0.7%) | 426 (252 – 552) | |||
| Factor H deficiency | 3 (0.4%) | 348 (12 – 468) | |||
| CD46 deficiency | 7 (1%) | 240 (144 – 456) | Absent CD46 expression on lymphocytes Reduced CD46 expression on lymphocytes |
85.7% 14.3% |
|
| C3 deficiency | 2 (0.3%) | 96 (72 – 120) | |||
| C7 deficiency | 1 (0.1%) | 264 | |||
| CHAPLE disease | 6 (0.9%) | 72 (24 – 168) | Absent CD55 expression on neutrophils | 100% | |
| Phenocopies of IEI | Good syndrome | 3 (0.4%) | 780 (636 – 828) | Hypogammaglobulinemia Profoundly decreased B cells Inverted CD4/CD8 ratio |
100% 100% 100% |
| Unclassified immunodeficiencies | 12 (1.8%) | 36 (7 – 516) | |||
*: naïve and memory T cells were analyzed in 72 patients.
**: WASp expression was assessed in 9 patients.
#: Th17, Il-17 production and STAT3 phosphorylation were assessed in 22 patients.
¥: Btk expression was assessed in 2 male patients.
§ : Phenotyping of circulating B-cell subpopulations was performed in 63 patients.
£ : NK-cell degranulation assay was performed in two patients.
ALPS, autoimmune lymphoproliferative syndrome; APDS, activated PI3K delta syndrome; ARPC1B, actin related protein 2/3 complex subunit 1B; Btk, Bruton’s tyrosine kinase; CGD, chronic granulomatous disease; CID, combined immunodeficiency; CHAPLE, complement hyperactivation angiopathic thrombosis and protein-losing enteropathy; CMC, chronic mucocutaneous candidiasis; CVID, common variable immunodeficiency; FHL, familial hemophagocytic lymphohistiocytosis; HLA, human leukocyte antigen; IPEX, immune dysregulation-polyendocrinopathy-enteropathy-x-linked; LRBA, LPS-responsive beige-like anchor protein; MHC, major histocompatibility complex; MSMD, mendelian susceptibility to mycobacterial disease, OS, Omenn syndrome; RIPK1, receptor-interacting serine/threonine-protein kinase 1; RTE, recent thymic emigrants; SCID, severe combined immunodeficiency; SIAD, selective IgA deficiency; sIg, serum immunoglobulins; TPP2, tripeptidyl peptidase 2; STAT, signal transducer and activator of transcription; WASp, Wiskott Aldrich syndrome protein.