New research links age-related gene changes to symptom decline

UCSF researchers have found that certain antiviral genes become less active over time in lupus, revealing why some patients see their symptoms fade as they age.

Lupus is a "classic" autoimmune disease. 

It causes the immune system's first-line viral defenses - known as interferons - to attack the body. Nearly every organ is at risk, leading to conditions like kidney and heart disease. 

But unlike many other autoimmune or chronic illnesses, lupus can improve as patients reach their 60s and 70s. 

I see my younger lupus patients in their 20s, 30s, and 40s every few months, monitoring them closely for signs of severe disease, but many of my older patients just once a year to touch base. If patients make it through those risky decades, they sometimes see a dramatic improvement."

Sarah Patterson, MD, Assistant Professor, Medicine, Division of Rheumatology, University of California - San Francisco

Now, Patterson and colleagues have published a study in ScienceTranslational Medicine that reveals how this works. 

By analyzing blood samples from patients across the age spectrum, the team discovered that aging turns down the activity of certain immune genes in people with lupus, leading to fewer interferons and other inflammatory proteins in the body.

The study found that in healthy adults, inflammation-related genes and proteins rose slowly over the years, a process that has been dubbed "inflammaging." In patients with lupus, however, the expression of these genes and proteins were abnormally high in mid-life but decreased as the decades went by. 

"Inflammaging seemed to be reversed in the lupus patients," said Chaz Langelier, MD, PhD, associate professor of medicine at UCSF and senior author of the paper. "But it wasn't fully reversed. The lupus patients still had a greater level of inflammatory signaling compared to healthy adults in older age."

That reversal reflected what Patterson has seen in her patients - a return to something approaching healthy older age. 

Next, the team intends to test whether drugs that block interferons are more or less effective in lupus patients at different ages. They also hope to extend the approach to understand other inflammation-related conditions, such as rheumatoid arthritis, COPD, and atherosclerosis.