Table 3.
Clinical/immunological characteristics of patients carrying pathogenic or of unknown significance variants related to risk factors for immune-dysregulation (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 | GnomAD MAF | Varsome | SCT | Status | ||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| L tot (/mmc) | T (%) | B (%) | NK(%) | DNT (%) | Il 10 (pg/mL) | IL18(pg/mL) | Vit B12 (ng/L) | IgG (mg/dL) | IgA(mg/dL) | IgM(mg/dL) | |||||||||||
| 1, M | ITP, AIHA |
ALPS-like | 4 | No | No | 2,298 | 53 | 44 | 0.6 | 0.4 | Na | Na | 732 | 1,197 | 52 | 106 |
TNFRSF13B
p. Ser194Ter |
\ | P | No | Alive |
| 2, F | ITP, AIHA, AIN | CVID | 3 | LPR, arthritis, recurrent fevers |
CD, ANA | 1,129 | 72 | 11 | 15 | 5 | 0,9 | 1,225 | 807 | 250 | 15 | 101 |
TNFRSF13B
p.Arg202His |
0,000729 | VUS | No | Alive |
| 3, M | ITP, AIHA |
ALPS-like | 1 | No | No | 4,375 | 57 | 31 | 9.5 | 2.7 | 11,2 | 800 | 1,005 | 1,785 | 84 | 157 | TNFRSF13B p.Gln57His | 0,00019 | VUS | No | Alive |
| 4, F | ITP, AIN |
CVID | 1 | Congenital malformations hydrocephalous BMF |
No | 310 | 52 | 35 | 0.5 | 0.8 | Na | Na | Na | Na | Na | Na |
TNFRSF13B
p.Arg202His |
0,000729 | VUS | Yes | Alive |
| 5, F | AIHA, AIN | ALPS | 1 | LPR | DAT, ASMA | 3,045 | 74 | 9 | 1.6 | 4.1 | 90 | 5,001 | 1,492 | 1,596 | 119 | 69 |
CASP10
p.Val410Ile |
0,0419 | B° | Yes | Alive |
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 anticoagulant; 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). °Abnormal functional test (29).