Table 2.
Clinical/immunological characteristics of patients carrying pathogenic/likely pathogenic variants related t o IEI (abnormal results in bold).
| Pt, sex | Type of cytopenia | Clinical phenotype | Age (years) at diagnosis | Other clinical signs | Other abnormalities | Lymphocyte subpopulations | ALPS Cytokines | Immunoglobulin levels | Variant° | GnomADMAF | Varsome | SCT | Status | ||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| L tot (/mmc) | T(%) | B(%) | NK (%) | DNT (%) | Il10 (pg/mL) | IL18(pg/mL) | Vit B12 (ng/L) | IgG (mg/dL) | IgA(mg/dL) | IgM(mg/dL) | |||||||||||
| 1, F | ITP, AIHA | ALPS | 7 | LPR | No | 1,900 | 83 | 6 | 9 | 2 | Na | Na | 1,581 | Na | 17 | 81 |
FAS
p.Glu256Gln |
\ | LP | No | Alive |
| 2, M | ITP, AIHA | ALPS | 6 | LPR | No | 1,757 | 78 | 15 | 16.4 | 5.8 | 35 | 550 | 921 | 2,000 | 100 | 43 |
FAS
p.Glu 245Lys |
\ | P | No | Alive |
| 3, F | ITP, AIHA | ALPS | 1 | LPR | No | 970 | 75 | 9.4 | 13.3 | 13 | 40 | 950 | 10,233 | 1716 | 120 | 93 |
FAS
p.Gln273His |
\ | P | No | Alive |
| 4, F | ITP, AIHA | ALPS | 12 | LPR arthritis, | Anti-parietal ab | 510 | 65 | 19 | 13.5 | 2.2 | 7 | 425 | 370 | 600 | 97 | 66 |
CTLA4
p.Cys58Sfs*13 |
\ | LP | No | Alive |
| 5, F | ITP, AIHA, AIN | ALPS | 2 | LPR arthritis, sclerosing cholangitis | Anti TPO, anti-Tg, CD, ANA, LAC | 670 | 87 | 5.3 | 2 | 4.7 | 0,2 | 265 | 999 | 3,556 | 199 | 244 |
IKBKG*
p.Glu125Lys |
0.00186 | LP | No | Alive |
| 6, F | ITP, AIHA, AIN | CVID | 2 | LPR | AI hepatitis, ANCA | 4,125 | 62 | 20 | 12.6 | 2.4 | 0 | 2,100 | 0 | 1,185 | 119 | 14 |
CARD11
p.Arg967Cys |
0.0000294 | VUS | No | Alive |
| 7, F | ITP, AIHA, AIN | ALPS | 5 | LPR | No | 5,060 | 97 | 2.6 | 1 | 5.1 | 14 | 5,250 | 374 | 254 | 13 | 299 |
ADA2
p.Thr187Pro/ p.Leu188Pro STAT3 p.Lys658Arg (mosaicisms) |
/;0.00000882;/ | LP/LP/LP | No | Dead |
| 8, M | ITP, AIHA | Idiopathic | 3 | No | Recurrent infections |
315 | 85 | 0.2 | 14 | 1.7 | 385 | 268 | 268 | 695 | 136 | 61 |
LIG4
p.Arg278His HOMO |
\ | P | Yes | Alive |
| 9, F | ITP, AIN | ALPS | 1 | LPR recurrent fevers |
DAT; CD, ASMA, AI hepatitis | 5,890 | 82 | 13 | 3.7 | 2.6 | Na | Na | Na | 955 | 54 | 67 |
LRBA
Arg655Ter HOMO |
0.0000147 | P | No | Alive |
| 10, F | ITP, AIN | ALPS | 11 | LPR recurrent fevers |
No | 1,690 | 73 | 19.9 | 1.1 | 6 | 79 | 1,175 | 2,000 | 1,689 | 293 | 110 |
FAS
p.Cys129Arg |
\ | P | No | Alive |
| 11, M | ITP, AIN | ALPS | 9 | LPR | CD | 60 | 61 | 28 | 0 | 3.5 | 4 | 550 | Na | Na | Na | Na |
STAT3^
p.Arg152Trp |
\ | LP | No | Alive |
| 12, M | ITP, AIN | ALPS-like | 2 | No | AI hepatitis, ENA | 730 | 45.8 | 38.2 | 8.1 | 3 | Na | Na | 1,100 | 1,815 | 26 | 20 |
CARD11
p.Val1009Ile |
0.000559 | VUS | Yes | Alive |
| 13, M | AIHA, AIN | ALPS-like | 2 | LPR, MAS | Cold agglutinins | 749 | 48 | 15 | 4.1 | 0.4 | Na | Na | 400 | 549 | 19 | 17 |
RAG1
p.Arg507Gln HOMO |
\ | LP | Yes | Alive |
IEI, inborn errors of immunity; AI hepatitis, autoimmune hepatitis; AIHA, autoimmune haemolytic anaemia; AIN, autoimmune neutropenia; ANA, antinuclear antibodies; ANCA, anti-neutrophil cytoplasmic antibodies; ASMA, anti-smooth-muscle antibodies; B, benign; BMF, bone marrow failure; CD, celiac disease; DAT, direct antiglobulin test; DNT, double negative T cells; ENA, extractable nuclear antigen antibodies; ES, Evans syndrome; SCT stem cell transplant; ITP, immune thrombocytopenia; LAC, lupus anti-coagulant; LP, likely pathogenic; MAC, multilineage autoimmune cytopenia; MAS, macrophage activation syndrome; Na, not available; P, pathogenic; Tg, thyroglobulin; TPO, thyroid peroxidase; VUS, variant of unknown significance; LPR, lymphoproliferation (Chronic, > 6 months, non-malignant, non-infectious lymphadenopathy or splenomegaly or both). °Variant zygosity is always meant as heterozygosity unless differently reported * A ratio of active/inactive × chromosome equal to 70:30, demonstrating that a moderate skewing was detected. This finding suggests a correlation between skewed × inactivation and phenotype in carriers of X-linked disease. ^ Gain of function (28).