Ancestry-based differences in the immune phenotype are associated with lupus activity.
JCI Insight
; 8(16)2023 08 22.
Article
em En
| MEDLINE
| ID: mdl-37606045
ABSTRACT
Systemic lupus erythematosus (SLE) affects 1 in 537 Black women, which is >2-fold more than White women. Black patients develop the disease at a younger age, have more severe symptoms, and have a greater chance of early mortality. We used a multiomics approach to uncover ancestry-associated immune alterations in patients with SLE and healthy controls that may contribute biologically to disease disparities. Cell composition, signaling, epigenetics, and proteomics were evaluated by mass cytometry; droplet-based single-cell transcriptomics and proteomics; and bead-based multiplex soluble mediator levels in plasma. We observed altered whole blood frequencies and enhanced activity in CD8+ T cells, B cells, monocytes, and DCs in Black patients with more active disease. Epigenetic modifications in CD8+ T cells (H3K27ac) could distinguish disease activity level in Black patients and differentiate Black from White patient samples. TLR3/4/7/8/9-related gene expression was elevated in immune cells from Black patients with SLE, and TLR7/8/9 and IFN-α phospho-signaling and cytokine responses were heightened even in immune cells from healthy Black control patients compared with White individuals. TLR stimulation of healthy immune cells recapitulated the ancestry-associated SLE immunophenotypes. This multiomic resource defines ancestry-associated immune phenotypes that differ between Black and White patients with SLE, which may influence the course and severity of SLE and other diseases.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Linfócitos B
/
Lúpus Eritematoso Sistêmico
Tipo de estudo:
Risk_factors_studies
Limite:
Female
/
Humans
Idioma:
En
Revista:
JCI Insight
Ano de publicação:
2023
Tipo de documento:
Article
País de afiliação:
Estados Unidos