Table 1. Summary of human LCK-IEI... | Rockefeller University Press

Table 1.

Summary of human LCK-IEI

Reference		LCK		Cellular			Clinical
Citation	Mutation	Protein expression	Functionality	T cells	B cells	Immunoglobulins	Age onset	Infectious	Noninfectious	Treatment and outcome
Hauck et al., 2012	c.1022T>C p.L341P	Decreased	Catalytically inactive	↓ Total T ↓ CD4⁺ T ↔ CD8⁺ T ↓ Treg ↑ γδT (ratio) ↑ TCM CD4⁺ T ↑ TEM CD8⁺ T	↓ Total B	↔ IgG ↔ IgA ↑ IgM ↔IgE	18 mo	Upper/lower respiratory; pneumonia; pneumatocele	Chronic diarrhea; nodular skin lesions; arthritis; inflamed hypodermis; retinal vasculitis; pericarditis; serositis; dsDNA⁺	HSCT; died at age 30 mo, 7 days after HSCT
Li et al., 2016	Intronic c.188-2A>G ΔExon 3	ND	ND	↓ CD4⁺ T	ND	ND	23 years 18 years 15 years	Childhood onset pneumonia; bacterial infections; HPV infections (EV-specific HPV and genital HPV)	Not observed; pityriasis	Unknown; one died – cranial tumor; one died – unknown reasons; one alive (ATR)
Lanz et al., 2023	c.1393T>C p.C465R	Decreased	Limited activity ↓ Ca²⁺-flux ↓ pZAP70 ↓ pERK	↓ Total T ↓ CD4⁺ T ↓ CD8⁺ T ↑ Treg ↑ γδT (ratio) ↑ TEM ↓ Naive	↑ Total B	↔ IgG ↔ IgA ↓ IgM ↔ IgE	6 mo	Oral and perianal candidiasis; EBV; ADV; CMV; respiratory infections	Not observed	Died at age 12 mo, respiratory failure
Keller et al., 2023	c.1129dupA p.S377KTer1 4	Decreased Truncated (lacks kinase domain)	Kinase dead	↓ Total T ↓ CD4⁺ T ↓ CD8⁺ T Treg (NL) ↑ γδT ↓ Naive	↔ B	Hypogamma-globulinemia	11 mo	Recurrent pneumonia; otitis media; skin infections	Not reported	HSCT Alive (ATR)
Keller et al., 2023	c.1129dupA p.S377KTer1 4	Decreased Truncated (lacks kinase domain)	Kinase dead	↓ Total T ↓ CD4⁺ T ↓ CD8⁺ T Treg (NL) ↑ γδT ↓ Naive	↑ Naive ↓ Class-switched ↓ Transitional B	↓ IgG IgA ? IgM ? IgE ?	42 mo	Recurrent pneumonia; otitis media; stool positive for cryptosporidium antigen; oral candidiasis; CMV; EBV	Recurrent erythematous and ulcerative plaque skin lesions; cutaneous and subcutaneous lesions	IVIG, HSCT; died at age 3.5 years, 20 days after HSCT
Lui et al., 2024	c.1318C>T; P440S	Decreased	Limited activity ↓ Ca²⁺-flux ↓ Phosphorylation of LCK Y394, CD3ζ, ZAP70	↓ Total T ↓ CD4⁺ T ↓ CD8⁺ T Treg (ND) ↑ γδT ↓ Naive	↔ Total B ↑ Naive B ↓ Memory B (ratio)	↓ IgG ↓ IgA ↔ IgM	Birth	Recurrent viral and fungal respiratory and gastrointestinal infections; HSV stomatitis; oral candidiasis; cryptosporidiosis; Norovirus; Salmonella enteritis	Chronic diarrhea	IVIG, HSCT; died at age 6.5 years, 3 mo after HSCT, pneumonia
Lui et al., 2024	c.1318C>T; P440S	Decreased		↓ Total T ↓ CD4⁺ T ↓ CD8⁺ T Treg (ND) ↑ γδT ↓ Naive	↔ Total B ↑ Naive B ↓ Memory B (ratio)	ND	1.5 mo		Chronic diarrhea	IVIG, HSCT; age 3 years, alive (ATR)

Reference		LCK		Cellular			Clinical
Citation	Mutation	Protein expression	Functionality	T cells	B cells	Immunoglobulins	Age onset	Infectious	Noninfectious	Treatment and outcome
Hauck et al., 2012	c.1022T>C p.L341P	Decreased	Catalytically inactive	↓ Total T ↓ CD4⁺ T ↔ CD8⁺ T ↓ Treg ↑ γδT (ratio) ↑ TCM CD4⁺ T ↑ TEM CD8⁺ T	↓ Total B	↔ IgG ↔ IgA ↑ IgM ↔IgE	18 mo	Upper/lower respiratory; pneumonia; pneumatocele	Chronic diarrhea; nodular skin lesions; arthritis; inflamed hypodermis; retinal vasculitis; pericarditis; serositis; dsDNA⁺	HSCT; died at age 30 mo, 7 days after HSCT
Li et al., 2016	Intronic c.188-2A>G ΔExon 3	ND	ND	↓ CD4⁺ T	ND	ND	23 years 18 years 15 years	Childhood onset pneumonia; bacterial infections; HPV infections (EV-specific HPV and genital HPV)	Not observed; pityriasis	Unknown; one died – cranial tumor; one died – unknown reasons; one alive (ATR)
Lanz et al., 2023	c.1393T>C p.C465R	Decreased	Limited activity ↓ Ca²⁺-flux ↓ pZAP70 ↓ pERK	↓ Total T ↓ CD4⁺ T ↓ CD8⁺ T ↑ Treg ↑ γδT (ratio) ↑ TEM ↓ Naive	↑ Total B	↔ IgG ↔ IgA ↓ IgM ↔ IgE	6 mo	Oral and perianal candidiasis; EBV; ADV; CMV; respiratory infections	Not observed	Died at age 12 mo, respiratory failure
Keller et al., 2023	c.1129dupA p.S377KTer1 4	Decreased Truncated (lacks kinase domain)	Kinase dead	↓ Total T ↓ CD4⁺ T ↓ CD8⁺ T Treg (NL) ↑ γδT ↓ Naive	↔ B	Hypogamma-globulinemia	11 mo	Recurrent pneumonia; otitis media; skin infections	Not reported	HSCT Alive (ATR)
Keller et al., 2023	c.1129dupA p.S377KTer1 4	Decreased Truncated (lacks kinase domain)	Kinase dead	↓ Total T ↓ CD4⁺ T ↓ CD8⁺ T Treg (NL) ↑ γδT ↓ Naive	↑ Naive ↓ Class-switched ↓ Transitional B	↓ IgG IgA ? IgM ? IgE ?	42 mo	Recurrent pneumonia; otitis media; stool positive for cryptosporidium antigen; oral candidiasis; CMV; EBV	Recurrent erythematous and ulcerative plaque skin lesions; cutaneous and subcutaneous lesions	IVIG, HSCT; died at age 3.5 years, 20 days after HSCT
Lui et al., 2024	c.1318C>T; P440S	Decreased	Limited activity ↓ Ca²⁺-flux ↓ Phosphorylation of LCK Y394, CD3ζ, ZAP70	↓ Total T ↓ CD4⁺ T ↓ CD8⁺ T Treg (ND) ↑ γδT ↓ Naive	↔ Total B ↑ Naive B ↓ Memory B (ratio)	↓ IgG ↓ IgA ↔ IgM	Birth	Recurrent viral and fungal respiratory and gastrointestinal infections; HSV stomatitis; oral candidiasis; cryptosporidiosis; Norovirus; Salmonella enteritis	Chronic diarrhea	IVIG, HSCT; died at age 6.5 years, 3 mo after HSCT, pneumonia
Lui et al., 2024	c.1318C>T; P440S	Decreased		↓ Total T ↓ CD4⁺ T ↓ CD8⁺ T Treg (ND) ↑ γδT ↓ Naive	↔ Total B ↑ Naive B ↓ Memory B (ratio)	ND	1.5 mo		Chronic diarrhea	IVIG, HSCT; age 3 years, alive (ATR)

ADV, Adenoviruses; ATR, At the time of report; EV, Epidermodysplasia verruciformis; HPV, human papillomavirus; IVIG, Intravenous immunoglobulin; ND, Not determined; TEM, T-effector memory.