Suppressor of Cytokine Signaling 1 Haploinsufficiency: A New Driver of Autoimmunity and Immunodysregulation

Meng Liu; Evan Hsu; Yan Du; Pui Y Lee

doi:10.1016/j.rdc.2023.06.003

Suppressor of Cytokine Signaling 1 Haploinsufficiency: A New Driver of Autoimmunity and Immunodysregulation

Rheum Dis Clin North Am. 2023 Nov;49(4):757-772. doi: 10.1016/j.rdc.2023.06.003. Epub 2023 Jul 21.

Authors

Meng Liu¹, Evan Hsu², Yan Du³, Pui Y Lee⁴

Affiliations

¹ Division of Immunology, Boston Children's Hospital and Harvard Medical School, Boston, MA, USA; Department of Rheumatology and Immunology, Guangdong Second Provincial General Hospital, Guangzhou, Guangdong, China.
² Division of Immunology, Boston Children's Hospital and Harvard Medical School, Boston, MA, USA.
³ Division of Immunology, Boston Children's Hospital and Harvard Medical School, Boston, MA, USA; Department of Rheumatology, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.
⁴ Division of Immunology, Boston Children's Hospital and Harvard Medical School, Boston, MA, USA. Electronic address: pui.lee@childrens.harvard.edu.

PMID: 37821194
DOI: 10.1016/j.rdc.2023.06.003

Abstract

Suppressor of cytokine signaling 1 (SOCS1) is a negative regulator of cytokine signaling that inhibits the activation of Janus kinases. A human disease caused by SOCS1 haploinsufficiency was first identified in 2020. To date, 18 cases of SOCS1 haploinsufficiency have been described. These patients experience enhanced activation of leukocytes and multiorgan system immunodysregulation, with immune-mediated cytopenia as the most common feature. In this review, the authors provide an overview on the biology of SOCS1 and summarize their knowledge of SOCS1 haploinsufficiency including genetics and clinical manifestations. They discuss the available treatment experience and outline an approach for the evaluation of suspected cases.

Keywords: Autoimmune disease; Autoimmunity; SOCS1; SOCS1 haploinsufficiency.

Publication types

Review

MeSH terms

Autoimmunity* / genetics
Cytokines / metabolism
Haploinsufficiency*
Humans
Suppressor of Cytokine Signaling 1 Protein / genetics
Suppressor of Cytokine Signaling Proteins

Substances

Suppressor of Cytokine Signaling 1 Protein
Suppressor of Cytokine Signaling Proteins
Cytokines