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Start Over Author "Krivan G" Journal nature genetics
2 results on '"Krivan G"'

1. Author Correction: Gain-of-function variants in SYK cause immune dysregulation and systemic inflammation in humans and mice.

Author

Wang L, Aschenbrenner D, Zeng Z, Cao X, Mayr D, Mehta M, Capitani M, Warner N, Pan J, Wang L, Li Q, Zuo T, Cohen-Kedar S, Lu J, Ardy RC, Mulder DJ, Dissanayake D, Peng K, Huang Z, Li X, Wang Y, Wang X, Li S, Bullers S, Gammage AN, Warnatz K, Schiefer AI, Krivan G, Goda V, Kahr WHA, Lemaire M, Lu CY, Siddiqui I, Surette MG, Kotlarz D, Engelhardt KR, Griffin HR, Rottapel R, Decaluwe H, Laxer RM, Proietti M, Hambleton S, Elcombe S, Guo CH, Grimbacher B, Dotan I, Ng SC, Freeman SA, Snapper SB, Klein C, Boztug K, Huang Y, Li D, Uhlig HH, and Muise AM

Published
2022
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2. Gain-of-function variants in SYK cause immune dysregulation and systemic inflammation in humans and mice.

Author

Wang L, Aschenbrenner D, Zeng Z, Cao X, Mayr D, Mehta M, Capitani M, Warner N, Pan J, Wang L, Li Q, Zuo T, Cohen-Kedar S, Lu J, Ardy RC, Mulder DJ, Dissanayake D, Peng K, Huang Z, Li X, Wang Y, Wang X, Li S, Bullers S, Gammage AN, Warnatz K, Schiefer AI, Krivan G, Goda V, Kahr WHA, Lemaire M, Lu CY, Siddiqui I, Surette MG, Kotlarz D, Engelhardt KR, Griffin HR, Rottapel R, Decaluwe H, Laxer RM, Proietti M, Hambleton S, Elcombe S, Guo CH, Grimbacher B, Dotan I, Ng SC, Freeman SA, Snapper SB, Klein C, Boztug K, Huang Y, Li D, Uhlig HH, and Muise AM

Subjects
Adult, Animals, Arthritis immunology, Arthritis pathology, Arthritis therapy, Base Sequence, Bone Marrow Transplantation, Colitis immunology, Colitis pathology, Colitis therapy, Dermatitis immunology, Dermatitis pathology, Dermatitis therapy, Family, Female, Gene Expression, Gene Knock-In Techniques, Humans, Infant, Lymphoma, Large B-Cell, Diffuse immunology, Lymphoma, Large B-Cell, Diffuse pathology, Lymphoma, Large B-Cell, Diffuse therapy, Male, Mice, Mice, Knockout, Middle Aged, Mutation, Pedigree, Protein Kinase Inhibitors pharmacology, Syk Kinase antagonists & inhibitors, Syk Kinase deficiency, Arthritis genetics, Colitis genetics, Dermatitis genetics, Lymphoma, Large B-Cell, Diffuse genetics, Syk Kinase genetics
Abstract

Spleen tyrosine kinase (SYK) is a critical immune signaling molecule and therapeutic target. We identified damaging monoallelic SYK variants in six patients with immune deficiency, multi-organ inflammatory disease such as colitis, arthritis and dermatitis, and diffuse large B cell lymphomas. The SYK variants increased phosphorylation and enhanced downstream signaling, indicating gain of function. A knock-in (SYK-Ser544Tyr) mouse model of a patient variant (p.Ser550Tyr) recapitulated aspects of the human disease that could be partially treated with a SYK inhibitor or transplantation of bone marrow from wild-type mice. Our studies demonstrate that SYK gain-of-function variants result in a potentially treatable form of inflammatory disease.

Published
2021
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