Table 2 Immunologic features of patients... | American Society of Hematology

Table 2

Immunologic features of patients with STAT3 gain-of-function mutations

		Normal range/healthy control median value	Patient 1 (K658N)	Patient 2 (K392R)	Patient 3 (M394T)
Leukocytes		3400-8200	7100	6900 (7500)*	5900
	Lymphocytes	1000-4500	1700	4278 (1270)*	820 ↓
	Monocytes	200-800	600	690 (370)*	570
	Neutrophils	1500-7500	4800	1750 (5830)*	4130
	Basophils	0-100	0	182 (0)*	80
	Eosinophils	100-400	0 ↓	10 (0)*↓	280
	Platelets	150 000-360 000	267 000	290 000 (266 000)*	271 000
	NK cells (CD3⁻CD16⁺/56⁺)	90-600 (12%)	12 (0.7%) ↓	128 (3%) (38, 0.5%)* ↓	40-90 (4-13%) ↓
	NK cell function and maturation		Normal	Normal	Normal
Dendritic cells
Plasmacytoid	lin⁻HLA-DR⁺CD123⁺CD11c⁻	0.1-0.3%	0.06% ↓	<0.01% ↓	0.01% ↓
Monocytoid	lin⁻HLA-DR⁺CD123⁻CD11c⁺	0.1-0.3%	0.2%	<0.01% ↓	0.73% ↑
CD3⁺ T cells		700-2100 (71%)	1462 (86%)	3507 (82%) (1092, 86%)*	474 (74%)
	TCRαβ⁺	94%	94%	45% ↓ (93%)*	97%
	TCRγδ ⁺	6%	6%	55% ↑ (7%)*	3%
	CD57⁺	21%	8.4%	65% ↑	65% ↑
	CD4⁻CD8⁻	4.2%	3.4%	30% (2.3%)* ↑	6%
	CD4⁻CD8⁻ TCRαβ⁺	<3.4%	1.6%	1%	5% ↑
	CD4⁻CD8⁻ TCRγδ +	NA	1.8%	29%↑	1%
CD3⁺CD4⁺ T cells		458-1406 (60%)	789 (54%)	666 (19%) ↓ (380, 34.8%)*	307 (48%) ↓
	CD45RO⁺	51%	46%	70% ↑	NA
	CD45RA⁺	47%	51%	26% ↓	18% ↓
	Ki-67⁺	2%	2,50%	1.80%	NA
	HLA-DR⁺	3%	29%	1.90%	NA
TCM	CCR7⁺CD45RA⁻	38%	44%	54% ↑	56% ↑
Naive	CCR7⁺CD45RA⁺	45%	50%	24% ↓	20% ↓
TEM	CCR7⁻CD45RA⁻	11%	5%	22% ↑	23% ↑
Temra	CCR7⁻CD45RA⁺	4%	1%	1%	2%
	Granzyme B⁺	1%	0.2%	1.9%	NA
Unstimulated	IFN-γ/TNF-α secretion	0%	0.2%	0.1%	Normal§
Stimulated	IFN-γ/TNF-α secretion	5%	7.3%	21.5% ↑	Normal§
Treg	FOXP3⁺CD25⁺	2.3-7.8%	1.45% ↓	(0.67%)* ↓	4.9%
Treg suppressive capacity			Low	Low	Normal
Th17†	CD69⁺IL17⁺	0.47-1.59%	0.13% ↓	(0.35%)* ↓	0.22 ↓
CD3⁺CD8⁺ T cells		200-1200 (51%)	570 (39%)	1790 (51%) (339, 31%)*	134 (21%)
	CD45RO⁺	41%	20%	5% ↓	NA
	CD45RA⁺	72%	76%	93% ↑	68%
	Ki-67⁺	1%	2,70%	16% ↑	NA
	HLA-DR⁺	3%	29%	56% ↑	NA
TCM	CCR7⁺CD45RA⁻	8%	11%	3%	13%
Naive	CCR7⁺CD45RA⁺	35%	62% ↑	8% ↓	45% ↑
TEM	CCR7⁻CD45RA⁻	27%	8% ↓	4% ↓	22%
Temra	CCR7⁻CD45RA⁺	33%	19%	86% ↑	21%
	Granzyme B⁺	11%	14.9%	0.2%	NA
Unstimulated	IFN-γ/TNF-α secretion	0%	0.1%	0.1%	Normal§
Stimulated	IFN-γ/TNF-α secretion	7.20%	4.50%	4.30%	Normal§
CD19⁺ B cells		70-230 (12%)	660 (9.3%)	174 (14%)*	80 (11%)
Transitional	CD38^hiIgM^hi	0.6-3.5%	3.4%	(0%)* ↓	0.4% ↓
Naive	CD27⁻IgD⁺	NA	70% ↑	(68%)* ↑	94% ↑
Mature B cells	CD21⁺	11-45%	84% ↑	(70%)* ↑	88 ↑
Memory	CD27⁺	15-45%	23%	(26%)*	4% ↓
Marginal zone-like	CD27⁺IgD⁺IgM⁺	7.2-30.8%	19.5% ↑	(24.9%)* ↑	2.9%
Switched memory	CD27⁺IgD⁻IgM⁻	6.5-29.2%	0.5% ↓	(0.5%)* ↓	<0.1 ↓
Plasmablasts	CD38⁺⁺IgM⁻	—	0.0%	(0.37%)*	0.5
Activated	CD38^lowCD21^low	0.6-3.5%	12.1% ↑	(22.5%)* ↑	11.7 ↑
Immunoglobulins (prior IVIG)
	IgG	6.8-15.0 g/L	5.8 ↓	2.8 ↓	0.16 ↓
	IgA	0.52-4.02 g/L	1.67	0.21	1.7
	IgM	0.47-2.84 g/L	3.38	1.44	0.6
	IgE	0-110 IU/L	0.7	0.5	<2
Complement	Classical., alternative, and mannan-binding lectin pathway hemolytic activities		Normal	Normal	Normal
Lymphocyte proliferative responses to mitogens	Phytohemagglutinin, concanavalin A, pokeweed mitogen		Normal	Normal	Normal
Lymphocyte chemotaxis			NA	NA	Normal
Specific antibodies against vaccine antigens	Tetanus, diphtheria, pneumococcal polysaccharide		Protective	Protective	Tetanus unprotective, others NA
Autoantibodies‡			TPO positive	Negative	Negative

		Normal range/healthy control median value	Patient 1 (K658N)	Patient 2 (K392R)	Patient 3 (M394T)
Leukocytes		3400-8200	7100	6900 (7500)*	5900
	Lymphocytes	1000-4500	1700	4278 (1270)*	820 ↓
	Monocytes	200-800	600	690 (370)*	570
	Neutrophils	1500-7500	4800	1750 (5830)*	4130
	Basophils	0-100	0	182 (0)*	80
	Eosinophils	100-400	0 ↓	10 (0)*↓	280
	Platelets	150 000-360 000	267 000	290 000 (266 000)*	271 000
	NK cells (CD3⁻CD16⁺/56⁺)	90-600 (12%)	12 (0.7%) ↓	128 (3%) (38, 0.5%)* ↓	40-90 (4-13%) ↓
	NK cell function and maturation		Normal	Normal	Normal
Dendritic cells
Plasmacytoid	lin⁻HLA-DR⁺CD123⁺CD11c⁻	0.1-0.3%	0.06% ↓	<0.01% ↓	0.01% ↓
Monocytoid	lin⁻HLA-DR⁺CD123⁻CD11c⁺	0.1-0.3%	0.2%	<0.01% ↓	0.73% ↑
CD3⁺ T cells		700-2100 (71%)	1462 (86%)	3507 (82%) (1092, 86%)*	474 (74%)
	TCRαβ⁺	94%	94%	45% ↓ (93%)*	97%
	TCRγδ ⁺	6%	6%	55% ↑ (7%)*	3%
	CD57⁺	21%	8.4%	65% ↑	65% ↑
	CD4⁻CD8⁻	4.2%	3.4%	30% (2.3%)* ↑	6%
	CD4⁻CD8⁻ TCRαβ⁺	<3.4%	1.6%	1%	5% ↑
	CD4⁻CD8⁻ TCRγδ +	NA	1.8%	29%↑	1%
CD3⁺CD4⁺ T cells		458-1406 (60%)	789 (54%)	666 (19%) ↓ (380, 34.8%)*	307 (48%) ↓
	CD45RO⁺	51%	46%	70% ↑	NA
	CD45RA⁺	47%	51%	26% ↓	18% ↓
	Ki-67⁺	2%	2,50%	1.80%	NA
	HLA-DR⁺	3%	29%	1.90%	NA
TCM	CCR7⁺CD45RA⁻	38%	44%	54% ↑	56% ↑
Naive	CCR7⁺CD45RA⁺	45%	50%	24% ↓	20% ↓
TEM	CCR7⁻CD45RA⁻	11%	5%	22% ↑	23% ↑
Temra	CCR7⁻CD45RA⁺	4%	1%	1%	2%
	Granzyme B⁺	1%	0.2%	1.9%	NA
Unstimulated	IFN-γ/TNF-α secretion	0%	0.2%	0.1%	Normal§
Stimulated	IFN-γ/TNF-α secretion	5%	7.3%	21.5% ↑	Normal§
Treg	FOXP3⁺CD25⁺	2.3-7.8%	1.45% ↓	(0.67%)* ↓	4.9%
Treg suppressive capacity			Low	Low	Normal
Th17†	CD69⁺IL17⁺	0.47-1.59%	0.13% ↓	(0.35%)* ↓	0.22 ↓
CD3⁺CD8⁺ T cells		200-1200 (51%)	570 (39%)	1790 (51%) (339, 31%)*	134 (21%)
	CD45RO⁺	41%	20%	5% ↓	NA
	CD45RA⁺	72%	76%	93% ↑	68%
	Ki-67⁺	1%	2,70%	16% ↑	NA
	HLA-DR⁺	3%	29%	56% ↑	NA
TCM	CCR7⁺CD45RA⁻	8%	11%	3%	13%
Naive	CCR7⁺CD45RA⁺	35%	62% ↑	8% ↓	45% ↑
TEM	CCR7⁻CD45RA⁻	27%	8% ↓	4% ↓	22%
Temra	CCR7⁻CD45RA⁺	33%	19%	86% ↑	21%
	Granzyme B⁺	11%	14.9%	0.2%	NA
Unstimulated	IFN-γ/TNF-α secretion	0%	0.1%	0.1%	Normal§
Stimulated	IFN-γ/TNF-α secretion	7.20%	4.50%	4.30%	Normal§
CD19⁺ B cells		70-230 (12%)	660 (9.3%)	174 (14%)*	80 (11%)
Transitional	CD38^hiIgM^hi	0.6-3.5%	3.4%	(0%)* ↓	0.4% ↓
Naive	CD27⁻IgD⁺	NA	70% ↑	(68%)* ↑	94% ↑
Mature B cells	CD21⁺	11-45%	84% ↑	(70%)* ↑	88 ↑
Memory	CD27⁺	15-45%	23%	(26%)*	4% ↓
Marginal zone-like	CD27⁺IgD⁺IgM⁺	7.2-30.8%	19.5% ↑	(24.9%)* ↑	2.9%
Switched memory	CD27⁺IgD⁻IgM⁻	6.5-29.2%	0.5% ↓	(0.5%)* ↓	<0.1 ↓
Plasmablasts	CD38⁺⁺IgM⁻	—	0.0%	(0.37%)*	0.5
Activated	CD38^lowCD21^low	0.6-3.5%	12.1% ↑	(22.5%)* ↑	11.7 ↑
Immunoglobulins (prior IVIG)
	IgG	6.8-15.0 g/L	5.8 ↓	2.8 ↓	0.16 ↓
	IgA	0.52-4.02 g/L	1.67	0.21	1.7
	IgM	0.47-2.84 g/L	3.38	1.44	0.6
	IgE	0-110 IU/L	0.7	0.5	<2
Complement	Classical., alternative, and mannan-binding lectin pathway hemolytic activities		Normal	Normal	Normal
Lymphocyte proliferative responses to mitogens	Phytohemagglutinin, concanavalin A, pokeweed mitogen		Normal	Normal	Normal
Lymphocyte chemotaxis			NA	NA	Normal
Specific antibodies against vaccine antigens	Tetanus, diphtheria, pneumococcal polysaccharide		Protective	Protective	Tetanus unprotective, others NA
Autoantibodies‡			TPO positive	Negative	Negative

CD3⁺ T-cell, CD4⁺ cell, CD8⁺ cell, and CD19⁺ cell numbers are indicated as absolute counts and relative percentages of all lymphocytes (%). Healthy control values are indicated either as absolute count ranges or medians (%).

↑, high value; ↓, low value; IVIG, intravenous immunoglobulin therapy; NA, not applicable; TCM, central memory T cell; TEM, effector memory T cell; Temra, effector memory RA T cell; Treg, regulatory T cell.

Tested before onset of lymphoproliferation at 12 y of age.

†

Of all activated CD3⁺CD4⁺ cells.

‡

For detailed specification, see supplemental data.

Test method differs from that of other patients.

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