Cellular and Molecular Diversity in Scleroderma

Hinchcliff, Monique; García-Milián, Rolando; Donato, Stefano Di; Dill, Karin E.; Bundschuh, Elizabeth; Galdo, Francesco Del

doi:10.1016/j.smim.2022.101648

Seminars in Immunology

2021

DOI: 10.1016/j.smim.2022.101648

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Cellular and Molecular Diversity in Scleroderma

Monique Hinchcliff

Rolando García-Milián²,

Stefano Di Donato³

et al.

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2021

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Distinct T cell chromatin landscapes in scleroderma subtypes

Dou

Zhao

Abe

et al. 2021

Preprint

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Systemic sclerosis (SSc; scleroderma) is a poorly understood autoimmune rheumatic disease that primarily affects women. The clinical hallmark is hardening of the skin, but internal organ dysfunction is the leading cause of death. Diagnosis and treatment are complicated by heterogeneity within the disease including variable lethality, fibrosis severity, serum autoantibody production, and internal organ involvement. Important gaps remain in our knowledge of the exact molecular and cellular pathways underlying distinct SSc subtypes. Herein, we identify genome-wide chromatin accessibility profiles of peripheral CD4+ T cells to distinguish and better understand the observed heterogeneity in SSc patients. We identify a link between serum anticentromere autoantibody (ACA) subtype and elevated levels of T helper 2 (Th2) cells and increased chromatin access at gene loci encoding fibrosis-driving Th2 cytokines IL4, IL13, and IL4 receptor. Biological sex followed by autoantibody subtype are the predominant variables associated with differences in CD4+ T cell epigenomic profiles, while mycophenolate mofetil treatment appeared to have no effect. These results suggest new mechanistic basis and therapeutic strategies to address SSc, especially the ACA+ subtype that is associated with pulmonary arterial hypertension.

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Distinct T cell chromatin landscapes in scleroderma subtypes

Dou

Zhao

Abe

et al. 2021

Preprint

View full text Add to dashboard Cite

show abstract

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Cellular and Molecular Diversity in Scleroderma

Cited by 1 publication

References 372 publications

Distinct T cell chromatin landscapes in scleroderma subtypes

Distinct T cell chromatin landscapes in scleroderma subtypes

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