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A T cell immune suppression signature distinguishes European American auto-antibody positive (ANA+) healthy individuals

ABSTRACT: Anti-nuclear antibody (ANA) positivity is a principal feature of individuals with an autoimmune disease, yet up to one in five healthy individuals are ANA+ and most will never develop clinical autoimmunity. Here, we show that immune profiles in ANA+ healthy individuals are altered, and differ by race. A suppressive immune signature distinguished by reduced T cell numbers and altered gene expression of HLA class I, IFN-associated, and apoptosis pathways, characterized European American (EA) ANA+ healthy individuals. In contrast, African American (AA) ANA+ healthy individuals had more elements of activation with increased CD69 gene expression on T cells and heightened pro-inflammatory cytokines. Increases in STAT4, IFNGR2 and STAT1 T cell transcripts and decreases in TGFBR1 gene expression in monocytes correlated with T cell expansion and clinical SLE. Thus, a suppressive immune signature in EA ANA+ healthy individuals may avert clinical autoimmune disease, which is associated with activation of Type I and II IFN pathways and T cell expansion.

ORGANISM(S): Homo sapiens

PROVIDER: GSE138400 | GEO | 2020/11/27

REPOSITORIES: GEO

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Project description:Background/Purpose: Systemic lupus erythematosus (SLE) is a complex multi-system autoimmune disease of uncertain etiology. Patients from different ancestral backgrounds demonstrate differences in clinical manifestations and autoantibody profiles. In this study we examined genome-wide transcriptional patterns in major immune cell subsets across different ancestral backgrounds. Methods: Peripheral blood was collected from 21 African-American (AA) and 21 European-American (EA) SLE patients, 5 AA controls, and 5 EA controls. CD4+ T-cells, CD8+ T-cells, monocytes and B cells were purified by flow sorting. Each cell subset from each subject was run on an Illumina HumanHT-12 V4 expression BeadChip array (n=208 arrays). Differentially expressed genes (DEGs) were determined by comparing cases and controls of the same ancestral background. Results: The overlap in DEG lists between different cell types from the same ancestral background was very modest (<1%). Typically between 5-10% of DEGs were shared when comparing the same cell type between different ancestral backgrounds (for ex. CD20 AA vs. CD20 EA). Quantitative measurement of global IFN-stimulated gene (ISG) expression revealed that AA subjects demonstrated more concordance across all studied cell types. Two subgroups of patients were identified based on the ISG expression profiles. One subgroup showed higher ISGs expression in all cell types, and the other subgroup had higherISG expression only in T and B lymphocytes but not in monocytes. The correlation of ISG expression with medication data revealed that only the B cells had lower ISG expression in patients taking immunosuppressants, while ISG expression in the other cell types did not differ based upon medication use. Conclusion: We find striking differences in gene expression between different immune cell subsets and between ancestral backgrounds in SLE patients. The IFN signature is diverse, with different transcripts represented in different cell populations, and signature-positive cell subsets differed in EA vs. AA patients. We also find that treatment with the immunosuppressive agents correlates with the down-regulation of B cell ISG expression, and this was not observed in other cell types. Peripheral blood was collected from 21 African-American (AA) and 21 European-American (EA) SLE patients, 5 AA controls, and 5 EA controls. CD4+ T-cells, CD8+ T-cells, monocytes and B cells were purified by flow sorting. Each cell subset from each subject was run on an Illumina HumanHT-12 V4 expression BeadChip array (n=208 arrays).

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A T cell immune suppression signature distinguishes European American auto-antibody positive (ANA+) healthy individuals

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