Dataset Information

Autoantibody-positive healthy individuals with lower lupus risk display a unique immune endotype.

ABSTRACT:

Background

Autoimmune diseases comprise a spectrum of illnesses and are on the rise worldwide. Although antinuclear antibodies (ANAs) are detected in many autoimmune diseases, up to 20% of healthy women are ANA-positive (ANA+) and most will never develop clinical symptoms. Furthermore, disease transition is higher among ANA+ African Americans compared with ANA+ European Americans.

Objective

We sought to determine the immune features that might define and prevent transition to clinical autoimmunity in ANA+ healthy individuals.

Methods

We comprehensively phenotyped immune profiles of African Americans and European Americans who are ANA-negative (ANA-) healthy, ANA+ healthy, or have SLE using single cell mass cytometry, next-generation RNA-sequencing, multiplex cytokine profiling, and phospho-signaling analyses.

Results

We found that, compared with both ANA- and ANA+ healthy individuals, patients with SLE of both races displayed T-cell expansion and elevated expression of type I and II interferon pathways. We discovered a unique immune signature that suggests a suppressive immune phenotype and reduced CD11C⁺ autoimmunity-associated B cells in healthy ANA+ European Americans that is absent in their SLE or even healthy ANA- counterparts, or among African American cohorts. In contrast, ANA+ healthy African Americans exhibited elevated expression of T-cell activation markers and higher plasma levels of IL-6 than did healthy ANA+ European Americans.

Conclusions

We propose that this novel immune signature identified in ANA+ healthy European Americans may protect them from T-cell expansion, heightened activation of interferon pathways, and disease transition.

SUBMITTER: Slight-Webb S

PROVIDER: S-EPMC7680268 | biostudies-literature |

REPOSITORIES: biostudies-literature

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