Table 1 Results of immunological characterization of the studied family. DNT, γ + δ + T and effector CD8 + memory cells are increased in II.2, III.2 and III.3; II.2 shows a B-cell memory deficiency
From: Immune dysregulation associated with co-occurring germline CBL and SH2B3 variants
II.1 | II.2 | III.1 | III.2 | III.3 (I-135) | Normal values for age (> 16 yrs.) | |
|---|---|---|---|---|---|---|
Immunophenotyping of peripheral blood cells | ||||||
WBC 10^9 /L | 6.54 | 5.24 | 5.41 | 7.01 | 3.85 | 3.60–10.50 |
Lymphocytes 10^9 /L | 1.92 | 0.81 | 2.07 | 2.05 | 1.51 | 1.2–4-1 |
Monocytes 10^9 /L | 0.40 | 0.46 | 0.42 | 0.42 | 0.35 | 0.10–0.90 |
CD3 + (PAN T), % (cells/μL) | 72% | 65.1% | 66% | 73.3% | 38.7% | 50–91% lymph |
CD3 + TCR α + β + , % | 96% | 87.5% | 95% | 89.3% | 90.4% | 36–98% CD3 + |
CD3 + TCR γ + δ + , % | 4% | 12.3% | 5% | 10.3% | 8.6% | 0.83–11% CD3 + |
CD3 + CD4-CD8-, (DNT) % | 0.7% | 2.9% | 2.7% | 2.4% | 2.6% | 0.57–3% CD3 + |
CD3 + CD4, % (cells/μL) | 43% (825) | 42.6% | 33% (683) | 27.4% (561) | 19.8% (298) | 28–64% CD3 + (500–2000) |
CD4 + CD45 RA + (Naïve), % | 21% | 23.3% | 50% | 48.5% | 37% | 16–100% CD4 + |
CD4 + CD45 RA-CCR7 + (Central memory), % | 55% | 70% | 42% | 48% | 56.2% | 18–95% CD4 + |
CD4 + CD45 RA-CCR7- (Effector memory), % | 20% | 6.6% | 10% | 3.4% | 6.8% | 1–23% CD4 + |
CD4 + CD45 RA + CCR7- (Terminal effector memory), % | 3% | 0.1% | < 0.1% | 0.08% | 0.08% | 0.0083–6.8% CD4 + |
CD4 + CD127 + CCR7 + CD25 + + (T reg) | 4 | n.d | 4 | n.d | n.d | 4–17% CD3 + |
CD3 + CD8, % (cells/μL) | 25% (480) | 10.8% | 26% (538) | 39.6% (811) | 16% (241) | 12–40% CD3 + (200–1200) |
CD8 + CD45 RA + (Naïve), % | 22% | 11.6% | 39% | 11.2% | 20.8% | 6–100% CD8 + |
CD8 + CD45 RA-CCR7 + (Central memory), % | 24% | 2.8% | 10% | 2.0% | 2.2% | 1–20% CD8 + |
CD8 + CD45 RA-CCR7- (Effector memory), % | 25% | 79.8% | 34% | 78.3% | 68.7% | 14–98% CD8 + |
CD8 + CD45 RA + CCR7- (Terminal effector memory), % | 28% | 5.6% | 18% | 8.5% | 8.4% | 7–53% CD8 + |
CD3-CD56 + CD16 + (NK), % | 17% | 25% | 21% | 12.7% | 44.8% | 5–49% WBC |
CD3 + CD56 + CD16 + (NKT), % | n.d | 4.2% | n.d | 3.8% | 1.7% | 1–18% WBC |
CD19 + (PAN B), % (cells/μL) | 10.66% (203) | 5.2% | 11.7% (242) | 8.7% (178) | 14.4% (217) | 4–28% (64–820) lymph |
CD19 + IGD + CD27- (B naïve) | 45% | 47.7% | 59% | 86.70% | 72.40% | 33–100% CD19 + |
CD19 + IgD + CD27 + (unswitched B memory) | 12% | 25.10% | 21% | 1.70% | 6% | 3–61% CD19 + |
CD19 + IgD-CD27 + (switched B memory) | 33% | 29.70 | 14% | 11.60% | 14% | 3–46% CD19 + |
CD19 + CD21 + CD38- (B CD21 + low) | 7% | 4.4% | 7% | 1.1% | 2.6% | 2–14% CD19 + |
CD19 + IgM + + CD38 + + (B transitional) | 3.6% | 2.3% | 1% | 9% | 7.1% | 0.27–24 CD19 + |
CD19 + IgM- + CD38 + + (B plasmablasts) | 0.3% | 0.10% | 0.3% | 0.10% | 0.02% | 0.7–6% CD19 + |
Lymphocyte proliferation with anti-CD3/anti-CD28 + rec. IL2 and with PHA | ||||||
Proliferating Lymphocytes with anti-CD3/anti-CD28 + rec. IL2 [%] | 76 | 97 | 79 | 66 | 94 | > 75% |
Proliferating Lymphocytes with PHA [%] | 92 | 96 | 98 | 95 | 96 | > 75% |
Fas-mediated apoptosis test | ||||||
Fas-mediated apoptosis (T lymphocyte survival, %) [< 82%] | 64% | 84; 831 | 75% | 95; 82a | n.d | < 82% |
TRECs expression, RTE, TFH | ||||||
TRECs expression | Normal | Low | Normal | Low | Low | |
CD4 + CD45RA + CD31 + (RTE) % | n.d | 13.4 | n.d | 32 | 27.3 | 7–100% |
CD4 + CD45R0 + CXCR5 + (TFH) % | n.d | 13.7 | n.d | 4.8 | 9.6 | 5–56% |
PhosphoS6 + lymphocytes | ||||||
CD3 + phospho S6 + , % | 3.58 | 5.1 | 8.51 | 8.2 | 5.25 | % Controls (n = 23) 7,3 (2,6–17,4%) median (10–90°pc) |
CD19 + phosphoS6 + , % | 13.1 | 5.1 | 15.8 | 5.8 | 13.2 | % Controls (n = 23) 6,4 (2,2–26,4%) median (10–90°pc) |