Mark Anderson, MD, PhD, professor in the School of Medicine, examines the genetic control of autoimmune diseases to gain a better understanding of the mechanisms by which immune tolerance is broken.
UCSF investigators have found an autoantibody biomarker for acquired lipodystrophy, paving the way for novel treatment options for this complex condition, which causes adipose tissue loss and metabolic complications.
“It’s pretty convincing that this is an autoimmune condition,” said study coauthor Mark S. Anderson, MD, PhD, director of the Diabetes Center at UCSF. “Now that this biomarker has been identified, patients with acquired lipodystrophy can be tested for it. This research also opens the door for testing people who are at risk for the disease. Typically, the autoantibodies show up before patients get really sick. Eventually, this discovery may lead to therapeutics.”
PLIN1 autoantibodies found in patients
The UCSF team used unbiased proteome-wide screening to identify autoantibodies to the adipocyte-specific lipid droplet protein perilipin 1 (PLIN1) in a murine model of autoimmune polyendocrine syndrome type 1 (APS1). They then tested for PLIN1 autoantibodies in two patients with acquired lipodystrophy and independent severe breaks in immune tolerance, including APS1. The researchers used a specific radioligand binding assay and indirect immunofluorescence on fat tissue to test the patients and control subjects.
The investigators identified autoantibodies to PLIN1 in the two patients, one of whom had the first reported case of APS1 with acquired lipodystrophy. The second patient developed lipodystrophy as a result of an immune-related adverse event following cancer immunotherapy.
“We showed that both patients had autoantibodies to PLIN1,” Anderson said. “That’s the target, and it’s expressed in the subcutaneous fat.”
Finding the link to autoimmunity
The researchers expanded the cohort and found that PLIN1 autoantibodies were specifically enriched in 17 of 46 patients with acquired generalized lipodystrophy (AGL), also known as Lawrence syndrome. Many of those patients also had one or more autoimmune conditions, including panniculitis. No one in the control group was positive for PLIN1 autoantibodies.
These findings suggest that PLIN1 autoantibodies are a marker of acquired autoimmune lipodystrophies and linked to a break in immune tolerance. Testing for this autoantibody determines whether patients have an autoimmune form of the disease – knowledge that can inform decision-making.
UCSF collaboration led to discovery
This work started with a collaboration between Anderson and Joe DeRisi, PhD, professor of biochemistry and biophysics and Howard Hughes Medical Institute Investigator at UCSF. “We developed a platform to screen patients’ blood for antibodies with unknown specificities that might be present in an autoimmune disease,” Anderson said. “The platform screens every protein in the entire human genome.” The first patient to participate in the study – who had APS1, acquired lipodystrophy and autoantibodies to PLIN1 – was found through this screening method.
To learn more
UCSF Endocrinology Clinic at Parnassus
Phone: (415) 353-2350 | Fax: (415) 353-2337
UCSF Endocrinology Clinic at Mount Zion
Phone: (415) 885-3868 | Fax: (415) 885-7724