Sphingolipid fingerprint predicts heart disease severity in African
American lupus patients

Date:
August 16, 2021
Source:
Medical University of South Carolina
Summary:
A potential biomarker predicting severity of heart disease in
African American lupus patients was identified in a study conducted
by a team of researchers.



FULL STORY ==========================================================================
A team of researchers at the Medical University of South Carolina (MUSC)
report in Frontiers in Immunology that they have identified a type of
fat known as a sphingolipid that could predict the severity of heart
disease in African American patients with lupus.


==========================================================================
The team was led by Samar M. Hammad, Ph.D., associate professor in the
MUSC College of Medicine, and the study was funded in part by a pilot
project grant from the South Carolina Clinical & Translational Research Institute.

"The most exciting finding of this study is that we may be able to find
another way to better diagnose and eventually treat the African American
lupus patients who are at increased risk of developing heart disease,"
said Hammad.

Systemic lupus erythematosus (SLE), or lupus, is a chronic autoimmune
disease that can affect many different organs in the body. Our immune
system typically acts like our personal bodyguard. When it senses danger
from a virus or infection, it attacks and eliminates the threat. In
patients with SLE, the "bodyguard" attacks and damages the person's own
cells, mistaking them as foreign invaders. As a result, patients with
SLE can develop complications, such as cardiovascular disease (CVD).

Cholesterol, a type of fat circulating in our blood, is carried on lipid particles called high-density lipoproteins (HDL, the good cholesterol
carrier) and low-density lipoprotein (LDL, the bad cholesterol carrier)
and typically used to screen for CVD. High levels of LDL cholesterol are commonly used to predict a patient's risk for developing heart disease
because this fat accumulates in the walls of blood vessels.

Despite being at an increased risk of CVD, healthy African Americans have
a lipid profile with higher HDL (good) cholesterol and lower triglyceride levels compared with healthy persons of European ancestry. Therefore,
the efficacy of the standard screening method for CVD has been called
into question for African American patients. Further, approximately 90%
of lupus patients are females, and African American women are three
times more likely than white women to develop severe symptoms associated
with SLE. Thus, the standard screening panels, developed with the white
patient in mind, lack efficacy for the African American patient. With
the standard method of screening for CVD potentially being unreliable
for African American SLE patients, additional biomarkers are needed to
improve health outcomes in this group.



========================================================================== Sphingolipids are molecules carried in the blood on lipoproteins. They
are important structural components of cells, can act as key
signaling molecules and, when disrupted, are associated with several
diseases. Recently, serum sphingolipids have been shown to be potential biomarkers for clinical lupus complications.

Notably, the Hammad lab previously found that the sphingolipid profile of healthy African Americans differs from that of healthy whites. They also observed differences in the sphingolipid profiles of African American
lupus patients with or without heart disease.

"Treatments for SLE and heart disease are often given as a
one-size-fits-all, and they can have major side effects for the patient,"
said Hammad.

The purpose of this study was to determine whether sphingolipids are
predictive biomarkers for preclinical CVD and CVD severity in African
American patients with SLE. At study start (visit 1) and after one year
(visit 2), the researchers measured levels of five different sphingolipid classes, with several sphingolipid species in each class, in plasma
samples of 51 patients with SLE but without a history of clinical heart disease.

Hammad and her lab established a methodology for profiling sphingolipids
in human plasma in 2010 that is now widely used in sphingolipid
studies. Using this method, Hammad and her team found that a particular
class of sphingolipid in the plasma samples, called lactosylceramide
(Lac-Cer), was positively correlated with the change in plaque area over
one year. Plaques are clumps of cholesterol found at injury sites of
walls of major arteries. Thus, higher levels of Lac-Cer are associated
with increased disease activity in African American patients with SLE.



========================================================================== "This finding showed us that the Lac-Cer levels in the circulation could
have predictive value for a patient," explained Hammad. "We could use
this as a readout for how a patient is progressing while on medication and
get a good indication of his or her heart disease." High LDL cholesterol content in the serum is typically used to determine the risk of developing heart disease. The study found no correlation between LDL concentrations
and the concentrations of the measured Lac-Cer species, indicating that
the traditional biomarker for heart disease was ineffective in predicting disease severity in the African American lupus population.

Ultimately, Hammad believes that studies like these emphasize the need
for teamwork between basic scientists and clinicians.

"I'm a basic scientist who has almost 20 years of experience in
investigating the role of sphingolipids in health and disease," said
Hammad. "This study was possible, thanks to the organized and well thought
out collection and banking of patient samples from the clinical side,
led by Dr. Jim Oates, division director of Rheumatology and Immunology."
Future objectives of the team will include determining whether their
findings can be applied to the general population.

"Using sphingolipids as a tool to complement other diagnostic
modalities will be important because SLE is often hard to
diagnose," said Hammad. "I think sphingolipids can play a
major role in the diagnosis, prognosis and treatment of lupus." ========================================================================== Story Source: Materials provided by
Medical_University_of_South_Carolina. Original written by Julia
Lefler. Note: Content may be edited for style and length.


========================================================================== Journal Reference:
1. Samar M. Hammad, Olivia C. Harden, Dulaney A. Wilson, Waleed
O. Twal,
Paul J. Nietert, Jim C. Oates. Plasma Sphingolipid Profile
Associated With Subclinical Atherosclerosis and Clinical
Disease Markers of Systemic Lupus Erythematosus: Potential
Predictive Value. Frontiers in Immunology, 2021; 12 DOI:
10.3389/fimmu.2021.694318 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2021/08/210816161346.htm

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