Somatic Reversion of Pathogenic Dock8 Variants Alters Lymphocyte Differentiation and Function to Effectively Cure Dock8 Deficiency

Somatic Reversion of Pathogenic Dock8 Variants Alters Lymphocyte Differentiation and Function to Effectively Cure Dock8 Deficiency Publisher Pubmed

Pillay BA^{1, 2} ; Fusaro M^{3, 4, 5} ; Gray PE^{6, 7, 8} ; Statham AL¹ ; Burnett L^{1, 2, 8} ; Bezrodnik L⁹ ; Kane A^{1, 2, 8, 10, 11, 12} ; Tong W^{8, 11} ; Abdo C¹³ ; Winter S^{3, 5, 14} ; Chevalier S⁴ ; Levy R^{3, 14, 15} ; Masson C^{3, 16} ; Schmitt Y^{3, 17, 18} Show All Authors

Pillay BA^{1, 2}
Fusaro M^{3, 4, 5}
Gray PE^{6, 7, 8}
Statham AL¹
Burnett L^{1, 2, 8}
Bezrodnik L⁹
Kane A^{1, 2, 8, 10, 11, 12}
Tong W^{8, 11}
Abdo C¹³
Winter S^{3, 5, 14}
Chevalier S⁴
Levy R^{3, 14, 15}
Masson C^{3, 16}
Schmitt Y^{3, 17, 18}
Bole C¹⁷
Malphettes M¹⁹
Macintyre E¹³
De Villartay JP²⁰
Ziegler JB^{6, 7, 8}
Smart JM²¹
Peake J²²
Aghamohammadi A²³
Hammarstrom L²⁴
Abolhassani H^{23, 24}
Picard C^{3, 4, 5, 14}
Fischer A^{3, 14, 25, 26}
Latour S⁵
Neven B^{14, 27}
Tangye SG^{1, 2, 8}
Ma CS^{1, 2, 8}

Source: Journal of Clinical Investigation Published:2021

Abstract

Inborn errors of immunity cause monogenic immune dysregulatory conditions such as severe and recurrent pathogen infection, inflammation, allergy, and malignancy. Somatic reversion refers to the spontaneous repair of a pathogenic germline genetic variant and has been reported to occur in a number of inborn errors of immunity, with a range of impacts on clinical outcomes of these conditions. DOCK8 deficiency due to biallelic inactivating mutations in DOCK8 causes a combined immunodeficiency characterized by severe bacterial, viral, and fungal infections, as well as allergic disease and some cancers. Here, we describe the clinical, genetic, and cellular features of 3 patients with biallelic DOCK8 variants who, following somatic reversion in multiple lymphocyte subsets, exhibited improved clinical features, including complete resolution of infection and allergic disease, and cure over time. Acquisition of DOCK8 expression restored defective lymphocyte signalling, survival and proliferation, as well as CD8+ T cell cytotoxicity, CD4+ T cell cytokine production, and memory B cell generation compared with typical DOCK8-deficient patients. Our temporal analysis of DOCK8-revertant and DOCK8-deficient cells within the same individual established mechanisms of clinical improvement in these patients following somatic reversion and revealed further nonredundant functions of DOCK8 in human lymphocyte biology. Last, our findings have significant implications for future therapeutic options for the treatment of DOCK8 deficiency. Copyright: © 2021, American Society for Clinical Investigation.

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Style	Citing Format
MLA	Pillay BA, et al.. "Somatic Reversion of Pathogenic Dock8 Variants Alters Lymphocyte Differentiation and Function to Effectively Cure Dock8 Deficiency." Journal of Clinical Investigation, vol. 131, no. 3, 2021, pp. -.
APA	Pillay BA, Fusaro M, Gray PE, Statham AL, Burnett L, Bezrodnik L, Kane A, Tong W, Abdo C, Winter S, Chevalier S, Levy R, Masson C, Schmitt Y, Bole C, Malphettes M, Macintyre E, De Villartay JP, Ziegler JB, ... Ma CS (2021). Somatic Reversion of Pathogenic Dock8 Variants Alters Lymphocyte Differentiation and Function to Effectively Cure Dock8 Deficiency. Journal of Clinical Investigation, 131(3), -.
Chicago	Pillay BA, Fusaro M, Gray PE, Statham AL, Burnett L, Bezrodnik L, Kane A, et al.. "Somatic Reversion of Pathogenic Dock8 Variants Alters Lymphocyte Differentiation and Function to Effectively Cure Dock8 Deficiency." Journal of Clinical Investigation 131, no. 3 (2021): -.
Harvard	Pillay BA et al. (2021) 'Somatic Reversion of Pathogenic Dock8 Variants Alters Lymphocyte Differentiation and Function to Effectively Cure Dock8 Deficiency', Journal of Clinical Investigation, 131(3), pp. -.
Vancouver	Pillay BA, Fusaro M, Gray PE, Statham AL, Burnett L, Bezrodnik L, et al.. Somatic Reversion of Pathogenic Dock8 Variants Alters Lymphocyte Differentiation and Function to Effectively Cure Dock8 Deficiency. Journal of Clinical Investigation. 2021;131(3):-.
BibTex	@article{ author = {Pillay BA and Fusaro M and Gray PE and Statham AL and Burnett L and Bezrodnik L and Kane A and Tong W and Abdo C and Winter S and Chevalier S and Levy R and Masson C and Schmitt Y and Bole C and Malphettes M and Macintyre E and De Villartay JP and Ziegler JB and Smart JM and Peake J and Aghamohammadi A and Hammarstrom L and Abolhassani H and Picard C and Fischer A and Latour S and Neven B and Tangye SG and Ma CS}, title = {Somatic Reversion of Pathogenic Dock8 Variants Alters Lymphocyte Differentiation and Function to Effectively Cure Dock8 Deficiency}, journal = {Journal of Clinical Investigation}, volume = {131}, number = {3}, pages = {-}, year = {2021} }
RIS	TY - JOUR AU - Pillay BA AU - Fusaro M AU - Gray PE AU - Statham AL AU - Burnett L AU - Bezrodnik L AU - Kane A AU - Tong W AU - Abdo C AU - Winter S AU - Chevalier S AU - Levy R AU - Masson C AU - Schmitt Y AU - Bole C AU - Malphettes M AU - Macintyre E AU - De Villartay JP AU - Ziegler JB AU - Smart JM AU - Peake J AU - Aghamohammadi A AU - Hammarstrom L AU - Abolhassani H AU - Picard C AU - Fischer A AU - Latour S AU - Neven B AU - Tangye SG AU - Ma CS TI - Somatic Reversion of Pathogenic Dock8 Variants Alters Lymphocyte Differentiation and Function to Effectively Cure Dock8 Deficiency JO - Journal of Clinical Investigation VL - 131 IS - 3 SP - EP - PY - 2021 ER -

Style

Citing Format

MLA

Pillay BA, et al.. "Somatic Reversion of Pathogenic Dock8 Variants Alters Lymphocyte Differentiation and Function to Effectively Cure Dock8 Deficiency." Journal of Clinical Investigation, vol. 131, no. 3, 2021, pp. -.

APA

Pillay BA, Fusaro M, Gray PE, Statham AL, Burnett L, Bezrodnik L, Kane A, Tong W, Abdo C, Winter S, Chevalier S, Levy R, Masson C, Schmitt Y, Bole C, Malphettes M, Macintyre E, De Villartay JP, Ziegler JB, ... Ma CS (2021). Somatic Reversion of Pathogenic Dock8 Variants Alters Lymphocyte Differentiation and Function to Effectively Cure Dock8 Deficiency. Journal of Clinical Investigation, 131(3), -.

Chicago

Pillay BA, Fusaro M, Gray PE, Statham AL, Burnett L, Bezrodnik L, Kane A, et al.. "Somatic Reversion of Pathogenic Dock8 Variants Alters Lymphocyte Differentiation and Function to Effectively Cure Dock8 Deficiency." Journal of Clinical Investigation 131, no. 3 (2021): -.

Harvard

Pillay BA et al. (2021) 'Somatic Reversion of Pathogenic Dock8 Variants Alters Lymphocyte Differentiation and Function to Effectively Cure Dock8 Deficiency', Journal of Clinical Investigation, 131(3), pp. -.

Vancouver

Pillay BA, Fusaro M, Gray PE, Statham AL, Burnett L, Bezrodnik L, et al.. Somatic Reversion of Pathogenic Dock8 Variants Alters Lymphocyte Differentiation and Function to Effectively Cure Dock8 Deficiency. Journal of Clinical Investigation. 2021;131(3):-.

BibTex

@article{ author = {Pillay BA and Fusaro M and Gray PE and Statham AL and Burnett L and Bezrodnik L and Kane A and Tong W and Abdo C and Winter S and Chevalier S and Levy R and Masson C and Schmitt Y and Bole C and Malphettes M and Macintyre E and De Villartay JP and Ziegler JB and Smart JM and Peake J and Aghamohammadi A and Hammarstrom L and Abolhassani H and Picard C and Fischer A and Latour S and Neven B and Tangye SG and Ma CS}, title = {Somatic Reversion of Pathogenic Dock8 Variants Alters Lymphocyte Differentiation and Function to Effectively Cure Dock8 Deficiency}, journal = {Journal of Clinical Investigation}, volume = {131}, number = {3}, pages = {-}, year = {2021} }

RIS

TY - JOUR
AU - Pillay BA
AU - Fusaro M
AU - Gray PE
AU - Statham AL
AU - Burnett L
AU - Bezrodnik L
AU - Kane A
AU - Tong W
AU - Abdo C
AU - Winter S
AU - Chevalier S
AU - Levy R
AU - Masson C
AU - Schmitt Y
AU - Bole C
AU - Malphettes M
AU - Macintyre E
AU - De Villartay JP
AU - Ziegler JB
AU - Smart JM
AU - Peake J
AU - Aghamohammadi A
AU - Hammarstrom L
AU - Abolhassani H
AU - Picard C
AU - Fischer A
AU - Latour S
AU - Neven B
AU - Tangye SG
AU - Ma CS
TI - Somatic Reversion of Pathogenic Dock8 Variants Alters Lymphocyte Differentiation and Function to Effectively Cure Dock8 Deficiency
JO - Journal of Clinical Investigation
VL - 131
IS - 3
SP -
EP -
PY - 2021
ER -

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