Table 1. Summary of clinical... | Rockefeller University Press

Table 1.

Summary of clinical characteristics of four patients with WAS gene mutation with large vessel vasculopathy in our cohort

	Patient 1	Patient 2	Patient 3	Patient 4
Age of presentation	5 years	3.5 years	11 years	11.8 years
Age of onset of initial symptoms	Infancy	2 years	8 years	11.4 years
Age at diagnosis of WAS	5 years	3.5 years	11 years	11.8 years
Age at the time of vasculitis manifestations	16 years	10 years	11 years	11.4 years
Presenting complaints	Acute febrile encephalopathy, seizures, right-sided lower motor neuron facial nerve palsy, bilateral lateral rectus palsy	Recurrent abdominal pain	Polyarthritis, recurrent abdominal pain, cough, hypertension, cardiac dysfunction	Abdominal pain, neck pain, left upper limb claudication
Lymphoproliferation	Present	Present	Present	Absent
Past infections
Bacterial infections	Sinopulmonary infections, pyogenic meningitis, pulmonary Tuberculosis	Sinopulmonary infections	None	None
Viral infections	None	Warts, extensive molluscum contagiosum	None	None
Autoimmune manifestations, if any	DCT negative autoimmune hemolytic anemia	Autoimmune hemolytic anemia	Arthritis, ANA negative, DCT negative	None
Eczema	++	++	−	−
IVIg prophylaxis at the time of vasculitis	Noncompliant	Noncompliant	Not initiated	Not initiated
EBV viral load	9720 copies/ml	38,880 copies/ml	Negative	5200 copies
CMV PCR, Serology:(HIV, HSV, HCV) and HBsAg	Negative	Negative	Negative	Negative
Investigations
MPV (fl)	6.7	6.8	7.4	6.1
Lowest platelet counts at presentation with vasculitis (×10⁹/L)	2.9	35	69	136
Immunoglobulin profile
IgG (g/L) (N:5–16)	12.4	7.5	6.67	14.9
IgM (g/L) (N:0.5–2)	1.35	0.24	0.47	0.50
IgA (g/L) (N:0.4–2)	0.59	5.68	1.92	5.83
IgE (KU/L; N<100)	370	6720	786	1256
Lymphocyte Subset analysis
CD3⁺ T lymphocytes (N: 55–75%)	61.9%	76.64%	56.9%	86.5%
CD19⁺ B lymphocytes (N: 10–30%)	7.6%	4.99%	30.58%	5.09%
CD16/56⁺ NK cells (N:4–23%)	7.3%	10.69%	11.81%	7.14%
CD3⁺ CD4⁺ T cell (N:27–53%)	36.25%	36.25%	69.75%	71.6%
CD3⁺ CD8⁺ T cell (N: 19–34%)	55.97%	55.97%	21.14%	19.4%
CD4:CD8 ratio (N: 0.9–3.6)	0.65	0.65	3.3	4.1
CD4⁺ CD127^– CD25⁺ (T_regs) (N: 5–10%)	4%	4%	14.45%	8.8%
WAS protein expression
Delta MFI	Patient: 1200	Patient: 281	Patient: 1495	Patient: 5128
Delta MFI	Control: 4300	Control: 1087	Control: 4761	Control: 7875
Stain index	Patient: 4	Patient: 4.17	Patient: 159	Patient: 145.46
Stain index	Control: 15.33	Control 8.68	Control: 428	Control: 65.68
WAS protein	Reduced	Reduced	Reduced	Normal
WAS gene variant	c.1021+2T>G, Intron 10-IVS 10+2 T>G	Exon 1 c.37C>T; p.R13*	Exon 2 c.256C>T, p.Arg86Cys	Exon 1 c.103 C>T, p.Leu35Phe
Arterial involvement	Thoracic and suprarenal part of abdominal aorta, critical focal luminal narrowing of brachiocephalic trunk at its origin with complete luminal occlusion of left subclavian artery and left common carotid artery	Abdominal aorta extending from diaphragmatic hiatus to bifurcation (L5 vertebral level). Variable length of proximal coeliac trunk, superior mesenteric artery and left renal artery showed fusiform dilatations	Suprarenal and renal segments and short infrarenal segment of the abdominal aorta, celiac artery origin, anterior right renal artery, posterior right renal artery	Long segment occlusion / tight stenosis of left subclavian artery.

	Patient 1	Patient 2	Patient 3	Patient 4
Age of presentation	5 years	3.5 years	11 years	11.8 years
Age of onset of initial symptoms	Infancy	2 years	8 years	11.4 years
Age at diagnosis of WAS	5 years	3.5 years	11 years	11.8 years
Age at the time of vasculitis manifestations	16 years	10 years	11 years	11.4 years
Presenting complaints	Acute febrile encephalopathy, seizures, right-sided lower motor neuron facial nerve palsy, bilateral lateral rectus palsy	Recurrent abdominal pain	Polyarthritis, recurrent abdominal pain, cough, hypertension, cardiac dysfunction	Abdominal pain, neck pain, left upper limb claudication
Lymphoproliferation	Present	Present	Present	Absent
Past infections
Bacterial infections	Sinopulmonary infections, pyogenic meningitis, pulmonary Tuberculosis	Sinopulmonary infections	None	None
Viral infections	None	Warts, extensive molluscum contagiosum	None	None
Autoimmune manifestations, if any	DCT negative autoimmune hemolytic anemia	Autoimmune hemolytic anemia	Arthritis, ANA negative, DCT negative	None
Eczema	++	++	−	−
IVIg prophylaxis at the time of vasculitis	Noncompliant	Noncompliant	Not initiated	Not initiated
EBV viral load	9720 copies/ml	38,880 copies/ml	Negative	5200 copies
CMV PCR, Serology:(HIV, HSV, HCV) and HBsAg	Negative	Negative	Negative	Negative
Investigations
MPV (fl)	6.7	6.8	7.4	6.1
Lowest platelet counts at presentation with vasculitis (×10⁹/L)	2.9	35	69	136
Immunoglobulin profile
IgG (g/L) (N:5–16)	12.4	7.5	6.67	14.9
IgM (g/L) (N:0.5–2)	1.35	0.24	0.47	0.50
IgA (g/L) (N:0.4–2)	0.59	5.68	1.92	5.83
IgE (KU/L; N<100)	370	6720	786	1256
Lymphocyte Subset analysis
CD3⁺ T lymphocytes (N: 55–75%)	61.9%	76.64%	56.9%	86.5%
CD19⁺ B lymphocytes (N: 10–30%)	7.6%	4.99%	30.58%	5.09%
CD16/56⁺ NK cells (N:4–23%)	7.3%	10.69%	11.81%	7.14%
CD3⁺ CD4⁺ T cell (N:27–53%)	36.25%	36.25%	69.75%	71.6%
CD3⁺ CD8⁺ T cell (N: 19–34%)	55.97%	55.97%	21.14%	19.4%
CD4:CD8 ratio (N: 0.9–3.6)	0.65	0.65	3.3	4.1
CD4⁺ CD127^– CD25⁺ (T_regs) (N: 5–10%)	4%	4%	14.45%	8.8%
WAS protein expression
Delta MFI	Patient: 1200	Patient: 281	Patient: 1495	Patient: 5128
Delta MFI	Control: 4300	Control: 1087	Control: 4761	Control: 7875
Stain index	Patient: 4	Patient: 4.17	Patient: 159	Patient: 145.46
Stain index	Control: 15.33	Control 8.68	Control: 428	Control: 65.68
WAS protein	Reduced	Reduced	Reduced	Normal
WAS gene variant	c.1021+2T>G, Intron 10-IVS 10+2 T>G	Exon 1 c.37C>T; p.R13*	Exon 2 c.256C>T, p.Arg86Cys	Exon 1 c.103 C>T, p.Leu35Phe
Arterial involvement	Thoracic and suprarenal part of abdominal aorta, critical focal luminal narrowing of brachiocephalic trunk at its origin with complete luminal occlusion of left subclavian artery and left common carotid artery	Abdominal aorta extending from diaphragmatic hiatus to bifurcation (L5 vertebral level). Variable length of proximal coeliac trunk, superior mesenteric artery and left renal artery showed fusiform dilatations	Suprarenal and renal segments and short infrarenal segment of the abdominal aorta, celiac artery origin, anterior right renal artery, posterior right renal artery	Long segment occlusion / tight stenosis of left subclavian artery.

Bold values indicate abnormal values.

N, age related normal values; WAS, Wiskott Aldrich syndrome; DCT, direct coombs test; fl, femtoliter; ANA, Anti nuclear antibody; IVIg, intravenous immunoglobulin; NK cell, natural killer cells, T_regs, Regulatory T cells; MFI, mean fluorescence index; EBV, Epstein barr virus; PCR, polymerase chain reaction, HIV-Human immunodeficiency virus; HSV, herpes simplex virus; HCV, Hepatitis C Virus; HBsAg, Hepatitis B surface antigen.

[ViewLarge]