Leading the way to a cure

Lupus Research Update: 2013 Volume 1

Volume 1, 2013 - Online Edition | In This Issue

Making the Connection Between Cardiovascular Disease and Lupus >
The ALR Welcomes New Board Member Daniel LaVecchia >
Two Compassionate Hearts Work to End Lupus >
2013 ALR TIL Grants Awarded >
Lupus News Corner >

Making the Connection Between Cardiovascular Disease and Lupus

Developing from a single cell, the human body becomes a wondrous and complex organism comprised of various systems that drive specific functions. In lupus, one of these systems — the immune system — malfunctions and can cause damage to the heart and other major organs.

With her ALR grant, Barbara Vilen, PhD, Associate Professor at the University of North Carolina, Chapel Hill, is directing a novel investigation that is looking at connections between lupus and cardiovascular disease — specifically atherosclerosis, or hardening of the arteries.

Why look at cardiovascular disease? Statistics reveal that the incidence of the disease is increased in lupus patients by 5-6 fold compared to the general population. Dr. Vilen explains the challenge: "While the numbers suggest that the immune system plays a role in atherosclerosis, the molecular basis underlying the immune trigger remains unknown."

Corroborations of the connection between lupus and cardiovascular disease came by Dr. Vilen's end-stage renal failure investigation in murine models. "Lights went on and we thought there is a connection between the immune complexes inducing BAFF (B-cell activating factor), BAFF driving kidney disease and BAFF driving lipid formation."

In her work, Dr. Vilen has observed an important clue: Immune complexes — which are formed from the integral binding of auto antibody to apoptotic debris — accumulated on the surface of immune cells.

Another piece of the puzzle is that cells undergoing apoptosis — the process of cell death naturally occurring in the body — generate internal debris that can also trigger the immune system in people with lupus. "Normally the body is highly efficient in removing these cells," said Dr. Vilen. "But in lupus patients, the system is broken."

Dr. Vilen suggests that part of the defect affects lipid biosynthesis, which is essential for the body's internal environment to remain stable. "Defects in lipid biosynthesis contribute to a variety of diseases... lead to the increased production of lipids, fatty cells, and foam cell formation — where immune cells absorb large amounts of fatty substance. These factors greatly contribute to atherosclerosis," said Dr. Vilen.

Thus, a person with lupus could be getting massive amounts of lipid biosynthesis from several different pathways.

In this complex framework, Dr. Vilen is looking to define if heightened BAFF dysregulates the production of lipocytes and fat cells, while promoting atherosclerosis. BAFF is a cytokine, which is known to be important to B-cell survival — and the overexpression of B-cells leads to lupus manifestations.

While many questions remain unanswered, Dr. Vilen's work is opening up new pathways for anti-BAFF treatment.

Dr. Vilen is vocal in her appreciation of the ALR for allowing her work to move forward: "The ALR enables scientists like me to approach lupus in different ways. This is an especially tough time for scientific funding, so I am all the more grateful to the ALR and its donors for making these types of investigations possible."

1.5 million

people in the U.S. have Lupus.

172 million

dollars committed to lupus research by the Lupus Research Alliance.

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