Novel Immune Signature May Protect Against Autoimmune Disease Transition

Researchers have identified a unique immune endotype in healthy European Americans who are autoantibody-positive that may protect them from transition to autoimmune disease.

“Although antinuclear antibodies (ANA) are detected in many autoimmune diseases, up to 20% of healthy women are ANA-positive (ANA+) and most will never develop clinical symptoms,” the researchers wrote. “Furthermore, disease transition is higher among ANA+ African Americans compared with ANA+ European Americans.”

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To identify immune features that may prevent transition to clinical autoimmunity among ANA+ healthy individuals, the researchers phenotyped immune profiles of African Americans and European Americans who are ANA-negative (ANA-) healthy, ANA+ healthy, or have systemic lupus erythematosus (SLE). 

Both African American and European American patients with SLE showed T-cell expansion and elevated expression of type I and II interferon pathways compared with ANA- and ANA+ healthy individuals, according to the study.

“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,” the researchers wrote.

Meanwhile, healthy African Americans who were ANA+ showed elevated expression of T-cell activation markers and higher plasma levels of interleukin-6 compared with healthy European Americans who were who were ANA+, the study found.

“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,” the researchers concluded.

—Jolynn Tumolo

Reference:

Slight-Webb S, Smith M, Bylinska A, et al. Autoantibody-positive healthy individuals with lower lupus risk display a unique immune endotype. J Allergy Clin Immunol. 2020;146(6):1419-1433. doi:10.1016/j.jaci.2020.04.047