Researchers from the University of Texas Southwestern Medical Centre recently announced that they discovered the first molecular biomarker for acquired generalised lipodystrophy (AGL), a rare disorder in which fat deposits are destroyed, causing patients to have dangerously low body fat, signs of accelerated ageing, and severe metabolic diseases including, diabetes and fatty liver.

The findings of the collaborative research, involving UT Southwestern along with the University of California, San Francisco, and institutions in France, Norway, and Russia, published in the journal Diabetes, could help diagnose patients more quickly and unlock new therapies for those with AGL, the researchers said.

 “The discovery of this autoantibody provides a new diagnostic tool for AGL patients and could potentially result in novel therapeutic options,” said Dr Abhimanyu Garg, Professor of Internal Medicine, Section Chief of Nutrition and Metabolic Diseases in the Division of Endocrinology, and Director of Metabolic Diseases in UT Southwestern’s Center for Human Nutrition.

AGL is a very rare disorder that usually affects children but can also occur in adults approximately 100 cases have been reported worldwide, making it difficult to study the commonalities among patients, as a result of which, the underlying cause has remained unclear, experts say.

For years, researchers have suspected the disorder is an autoimmune condition, in which a person’s immune system attacks the body. However, they had been unable to pinpoint any unusual or unique autoantibodies in AGL patients.

Dr Garg and his colleagues utilised their UT Southwestern biorepository containing blood, DNA, and clinical data collected from 46 patients with AGL over the past 30 years.

“We now have the largest collection of data on AGL patients in the world,” Dr Garg said. “The banked samples from these patients were key to our new discovery.”

Analysing from a pool of over 19,500 different human proteins in the blood samples from the patients and healthy controls, the research team found that perilipin-1, known to play a role in the storage of fat molecules in fat cells, autoantibody is the key differentiating people with AGL from those without the disease.

The researchers found that of the 46 AGL patients to whose blood samples they had access, the autoantibody was present in 17 of them, while it was absent in all the controls.

The researchers concluded that the perilipin-1 autoantibody, which directs the immune system to attack the protein and thus harm fat cells, may play a role in AGL.

Further detailed profiling of the blood samples of the perilipin-1 autoantibody-containing patients revealed that people who were suffering from AGrohitL with panniculitis, a subtype of AGLwere even more likely to have them.

It may be noted that panniculitis is a process whereby immune cells infiltrate fat tissue, resulting in the destruction and death of fat cells. The researchers also found that laboratory mice are known to develop AGL-like disease and also had the autoantibody to perilipin-1.

Pointing out that more work is needed to understand the prevalence of the perilipin-1 autoantibody among patients with AGL and related disorders, the researchers noted that further research is required to explore whether an immunotherapy drug or procedure could remove or block the autoantibody to treat those developing AGL.