Leading the way to a cure

Lupus Research Update: 2012 Volume 4

Volume 4, 2012 - Online Edition | In This Issue

2012: A Year of Tremendous Achievement >
Silicon Chip May Offer More Complete Diagnosis >
Insights into Lupus: Looking at Chromosomal Variations >
Collaboration Aims to Swiftly Develop New Lupus Therapies >
Faces of Lupus: A Mother and Daughter Story >
Lupus News Corner >

Insights into Lupus: Looking at Chromosomal Variations

To understand the complexities of lupus and its varied symptoms, many experts need to simultaneously approach the disease from a variety of angles.

One promising ALR-funded investigation is currently being conducted by Michael Denny, PhD, at Temple University in Philadelphia, PA, which focuses on neutrophils — the most abundant type of white blood cells in humans.

In the first year of his ALR grant, Dr. Denny has broadened the understanding of lupus by identifying an abnormal pool of neutrophils in people with the disease. "These cells — called low-density granulocytes (LDGs) — may contribute to disease manifestations like skin rashes and vasculitis," explained Dr. Denny.

In an effort to more clearly define the differences between LDGs and normal density neutrophils, Dr. Denny and his team developed a selection technique to isolate both from the blood of patients with lupus.

With that major accomplishment behind him, Dr. Denny set out to establish whether a genetic component to LDGs exists. "Little is known about the origins of these LDGs," he made plain.

So, next he tested for chromosomal variations in patients' LDGs relative to their own normal density neutrophils. Any alterations between the genomic composition of these two lineages would strongly suggest that a genetic root underlays this abnormality — and on average that's what Dr. Denny found.

Specifically, the research revealed that the neutrophils isolated from people without the disease had a similar level of copy number variations as the normal density neutrophils isolated from lupus patients. In contrast, the LDGs isolated from these same patients had a two-fold increase in copy number variations relative to these normal density neutrophils.

By identifying the underlying mechanisms responsible for the abnormalities in neutrophils, Dr. Denny has hope of bringing lupus research closer to developing more targeted therapies for the disease: "One of the aspects I find fascinating is if the LDGs are developmentally regulated — that they come from some abnormal development process — that may mean we can go back and treat them in the developmental stage, before damage occurs."

In their second year of ALR funding, Dr. Denny and his team will attempt to pinpoint the genesis of the alterations that occur within the cycle of cell development.

About his long association with the ALR, Dr. Denny said: "No one could have predicted how my research has progressed — but if not for ALR funding, I don’t think that it would have been done. You can’t underestimate that level of support and what it means to lupus research — let alone the 1.5 million Americans living with the disease."

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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