狼疮作为一种顽固的自身免疫性疾病，其活动强度似乎随年龄增长而减弱。尽管该病在年轻患者中会通过失控的干扰素信号传导猛烈攻击器官，但加州大学旧金山分校（UCSF）的研究人员发现，衰老过程本身可能自然缓和这些免疫系统攻击。通过比较不同年龄组的免疫标志物，研究团队发现狼疮患者随着年龄增长炎症反应实际呈下降趋势，这与典型的"炎性衰老"现象全然不同。这一意外转折为开发针对年龄的新型疗法开启全新路径，不仅为控制狼疮，更为管理其他炎症性疾病带来希望。
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1. 保留所有专业术语：自身
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," said Sarah Patterson, MD, assistant professor of medicine in the division of rheumatology at UCSF. "If patients make it through those risky decades, they sometimes see a dramatic improvement."
Now, Patterson and colleagues have published a study in Science Translational 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.
Authors: Other UCSF authors are Rithwik Narendra, Hoang Van Phan, Ana Almonte-Loya, Emily C. Lydon, MD, Christina Love, Michiko Shimoda, PhD, Padmini Deosthale, MS, Lenka Maliskova, Walter Eckalbar, PhD, Gabriela K. Fragiadakis, PhD, Jinoos Yazdany, MD, MPH, Maria Dall'Era, MD, Patricia Katz, PhD, Chun Jimmie Ye, PhD, and Marina Sirota, PhD. For a complete author list see the paper.
Funding: This work was funded by the National Institutes of Health (R01 AR069616, K23AT011768, P30 AI027763), the US Centers for Disease Control and Prevention (CDC), and the Chan Zuckerberg Biohub.