Download Lupus and Infection - Lupus Research Alliance

Volume 2, 2015
prevent.treat.cure.
> Lupus and Infection — A Closer Look
> A Father’s Quest for Answers — Perspectives from
Our Newest Board Member
> Lupus Insight Prize Awarded — To George Tsokos
> Looking for a New Way to Fight Lupus?
> May — Lupus Awareness Month
Lupus and Infection
A Closer Look
Lupus flare or infection? This is the question that puzzles physicians like Meggan Mackay, M.D., M.S., of the Feinstein
Institute for Medical Research, when their patients present symptoms that could be attributed to either an infection or
a lupus flare.
Being a physician and a researcher, Dr. Mackay knows that shortening the time it
takes doctors to accurately diagnose what’s going on with their patients is critical.
The longer it takes to begin appropriate therapies, the more damage is done to
healthy tissue.
This is why differentiating between infection and lupus activity (also known as
flares) is the aim of her research, which began with an Alliance for Lupus Research
(ALR) pilot research grant in 2008.
Before delving into the specifics of her investigation, Dr. Mackay offered some
insights into lupus itself. “Lupus is an illness that is caused by an over-active immune
system. When most people think of the immune system, it is in regard to its primary
function to ward off infection, which it does. It also fights other diseases and acts as a
constant surveillance system for viruses, bacteria and cancer cells that shouldn’t be there,”
she explained.
In lupus there are a lot of abnormal immune cells, so the immune system does not
work as it should. “It’s over-reactive to self, both attacking the body and not providing
the normal level of immune surveillance to protect against infection,” said Dr. Mackay.
Dr. Meggan Mackay
1
For this reason, lupus patients are particularly susceptible to infections, such as “encapsulated” organisms like
streptococcus. “Patients come in with a fever, which turns out to be due to a strep infection. Then we may find they actually
have lupus,” Dr. Mackay said.
Complicating matters is the fact that the medications used to treat lupus also make patients more susceptible to
infections.
Lupus patients are most commonly treated with steroids because they are the fastest working, most powerful antiinflammatory medications currently available. “Within hours, steroids can shut down the production of pro-inflammatory
proteins that cause lupus flares,” said Dr. Mackay. “But steroids also shut down proteins that protect the body against
infection.”
Unfortunately, for lupus patients, steroids aren’t the only culprits. Many of the medications
used in lupus are immunosuppressive — especially those used to treat serious lupus
activity that affects major organs, including the kidney, brain, cardiovascular system, and
lungs. These medications also decrease the immune response, making patients much more
likely to get infections.
When confronted with a lupus patient who feels ill and has a fever it is usually very
difficult to distinguish between lupus flare and infection since both often have similar
symptoms. Dr. Mackay explains that “We frequently need to treat for both lupus flare and
infection, even when treating lupus may make it more difficult for an infection to respond to
antibiotics and may increase the risk of additional infections, but we have to take that risk.” It’s all
a matter of timing, because it can take days for culture results to determine if a patient is
infected or for blood tests that may suggest a lupus flare — and during that time, untreated
lupus and/or infection can wreak havoc on healthy tissue.
"It has taken time but our
study did find definite
differences between
lupus patients who flared
and lupus patients who
were infected."
– Dr. Meggan Mackay
The ALR funding she received allowed Dr. Mackay to write a protocol that looks for a way to differentiate between
lupus flare and infection. With the help of a geneticist — Peter K. Gregersen, M.D., also from the Feinstein Institute,
— Dr. Mackay set out to see what kinds of genes were being expressed in the blood of lupus patients who are sick
and have a fever to identify differences in those who had infections and those who had flares. “It has taken time but our
study did find definite differences in gene expression between lupus patients who flared and lupus patients who were infected,”
said Dr. Mackay.
Today Dr. Mackay is looking to replicate this work in a much larger group. The idea would be to develop a test that
could be done at the bedside to differentiate between infection and lupus flare. “Knowing means we could tailor the
treatment faster, reducing the risk of complications and death,” she said.
Dr. Mackay is enthusiastic about the ALR: “The organization is vital to lupus research. Without this kind of support for pilot
projects, many investigations would never get off the ground. To young scientists coming up in the field, that’s really important.
And the ALR is also essential to established investigators who may be looking to study a novel or unconventional line of inquiry.”
Dr. Mackay had no personal connection to lupus, but while she was Chief Resident at Jacobi Medical Center and
working in the Intensive Care Unit, she met two patients who changed the course of her career. The women were
very ill and very young. Both were in their early 20s and both died from lupus complications within 24 hours of being
admitted into the ICU.
Until that point, Dr. Mackay had focused on internal medicine — but these patients helped guide her to a rheumatology
fellowship under the tutelage of the renowned Dr. Betty Diamond, who leads the Center for Autoimmune and
Musculoskeletal Disease at the Feinstein Institute. “I’ve always been drawn to lupus patients,” Dr. Mackay said. “They
are often women, young women, and they are deeply affected by this disease. We still do not understand what causes
lupus and there is a great need for better treatments. This is why I went into clinical research.”
2
|
Research Portfolio Summary
2
A Father’s Quest for Answers
Perspectives from Our Newest Board Member
The ALR is pleased and honored to welcome William J. Wolfe, co-founder,
President, and CEO of First Washington Realty, Inc., to our Board of Directors. Not
only does he bring decades of top-flight business savvy to the table — Mr. Wolfe
knows what it is like to cope with the unpredictable nature of lupus.
His daughter — Jacqueline Wolfe Maggi — has had the disease for at least the past
15 years.
“Jacqueline began experiencing symptoms as a young teen, with ups and downs until her
early 20s. Then her disease flared terribly and it was obviously lupus,” said Mr. Wolfe.
The lack of viable treatment options fueled this family’s frustration — and
Jacqueline’s lupus was particularly difficult to treat. “Not only did my daughter have
bad reactions to a series of medications, she is allergic to polysorbate, an emulsifier that is
used in a number of medications,” he continued.
As Jacqueline’s disease progressed, Mr. Wolfe gave himself the arduous task of
learning as much as he possibly could from those who know the most about the
disease — the most brilliant scientists, clinicians, and technicians in the world,
including members of the ALR’s Scientific Advisory Board.
Bill Wolfe
He is also a man on a timeline. “A cure is a fantastic idea... but a cure may be 15-20 years away and I don’t want to see my
daughter, or anyone else, suffer for that amount of time” said Mr. Wolfe.
So, this loving father started his own lupus research organization called Lupus Therapeutics. The timing was perfect.
Just as Mr. Wolfe was developing a plan to conduct clinical trials, the ALR was working on a new initiative to
“repurpose” drugs that had already been approved by the FDA. Repurposing is a revolutionary concept, and if one or
two of these drugs is efficacious in treating lupus, it will save time, money and, more importantly, lives.
“Woody Johnson and Ken Farber came to me last year and said let’s put these two organizations together — and we’re off and
running,” Mr. Wolfe said with unabashed enthusiasm.
The ALR was eager to incorporate Mr. Wolfe’s organization into our efforts to accelerate the discovery of new and
more effective treatments for lupus patients. We are launching a multi-year $100 million major donor campaign called
Lupus Therapeutics. The name acknowledges Mr. Wolfe’s invaluable contributions to the ALR.
Passionate. Determined. Dedicated. Optimistic. All of these words aptly describe Mr. Wolfe’s approach to fighting
lupus. These days he travels the country meeting people whose lives — like his own — have been shaped by lupus.
“I’m up front. I ask them to step up to the plate,” said Mr. Wolfe. “Other organizations have been extremely successful in
reaching out to their patient community. That’s what I hope to do for the ALR.”
Mr. Wolfe is right. We need to engage our entire community to produce more options, and the ALR is grateful to have
such a staunch supporter on our side.
William J. Wolfe is the co-founder, President and CEO of First Washington Realty, Inc., a privately held real estate
investment advisory and management firm which specializes in the acquisition, ownership, and management of
neighborhood and community shopping centers located in densely populated areas throughout the United States.
Prior to entering the real estate business, Mr. Wolfe served in the executive office of the President of the United States,
in the administration of President Jimmy Carter.
He currently is on the board of trustees of the Washington Institute for Near East Policy, the Alternatives for Youth
Foundation, and the World Presidents’ Organization.
Mr. Wolfe received his bachelor’s degree from Clark University and his master’s degree from Harvard University.
3
Lupus Insight Prize Awarded
To George Tsokos
This year’s Lupus Insight Prize goes to George Tsokos, M.D., Chief of
the Rheumatology Division at Beth Israel Deaconess Medical Center and
Professor of Medicine at Harvard Medical School.
Dr. Tsokos is widely recognized as one of the foremost leaders of modern
lupus research with landmark discoveries that have brought understanding
of lupus to new levels, by shedding new light on how the disease develops
and progresses over time. He is the editor of the peer-reviewed journal
Clinical Immunology, he is also on the editorial boards of more than 30
publications, has published over 400 papers, and has received numerous
awards and honors recognizing his contributions to the field.
The prize will help Dr. Tsokos to study the molecular link between the
immune system and the kidney damage seen frequently in patients with
lupus nephritis, a dangerous complication of lupus.
Dr. Tsokos will also work to develop a targeted delivery of drugs to block
the action of a single enzyme specifically to kidney cells.
In earlier studies, Dr. Tsokos has shown that the enzyme calcium
calmodulin kinase 4 (CaMK4) plays a role in autoimmunity and
inflammation in lupus. In murine models, Dr. Tsokos discovered
that CaMK4 also damages kidney cells so they can no longer
prevent proteins from leaking out of the kidneys into the urine. This
leakage, known as proteinuria, is a key indicator of lupus nephritis
and can lead to edema — swelling of various parts of the body from
a build-up of excess fluid.
Now, he will evaluate highly targeted delivery of drugs that inhibit
CaMK4 while honing in on just those cells impacted by the enzyme.
Dr. George Tsokos and Dr.Peter Lipsky
“Our work has potential to significantly improve treatment of lupus
nephritis, a condition that can lead to kidney failure, the need for chronic
dialysis or kidney transplantation and potentially death,” commented Dr.
Tsokos. “The administration of a drug targeting only those cells impacted
by one enzyme should relieve lupus nephritis symptoms while minimizing
debilitating side effects common with current treatment.”
The Lupus Insight Prize is a collaborative initiative sponsored by the Alliance for Lupus Research, the Lupus Foundation
of America and the Lupus Research Institute. The prize provides $200,000 for use in innovative research on lupus.
The three organizations presented Dr. Tsokos with the Lupus Insight Prize during a formal ceremony on June 24 at the
annual meeting of the Federation of Clinical Immunology Societies (FOCIS) in San Diego.
There, leading clinicians and researchers shared the latest breakthroughs in lupus and other diseases affecting the
immune system. At the ceremony, Dr. Tsokos shared plans about his project and its implications for treating lupus
nephritis.
4
Looking for a New Way to Fight Lupus?
Give Generously — The ALR transforms gifts into answers for the 1.5 million Americans who have the disease. And it
is compassionate people like you who help us make gains by propelling the world’s most pioneering lupus research.
Make your special gift today by clicking here!
Shop and Sell — WebThriftStore is an online thrift shop that lets donors sell
their unwanted things to benefit the charity of their choice. WebThriftStore
turns stuff into cash for charities, tax deductions for donors, and bargains for buyers. It’s a way for buyers and sellers to
do good, and the proceeds will go to the ALR!
Click here to learn more.
Donate Your Vehicle — You can donate your used car, truck, motorcycle, or other vehicle to the ALR. We will tow your
vehicle at no cost to you.
For more information, call us at 855-33-LUPUS or click here.
Think of the Future... Make a Planned Gift — One of the simplest and most powerful ways to make a planned gift is to
add the ALR to your will. Making a bequest can have a significant impact on the tax status of your estate, and it can help
ensure that your legacy will secure the future of the most pioneering lupus research in the world. Consult with your
attorney about including the ALR in your will and other planned giving options.
Click here for more giving options!
5
May — Lupus Awareness Month
The ALR marks its calendar each May for an all-important observance
— Lupus Awareness Month. And this year we used various forms of
social media — Twitter, Facebook, and Instagram — to broaden our
reach in getting out this key message:
Nearly 5 million people worldwide have #lupus and there is still no
cure. Help us lead the way to one. #OneLineOneDay alr.org.
We asked all of our friends and associates to take this simple action to
increase lupus awareness in May... and beyond.
We also introduced two new limited-edition items in the ALR Online
Store: Lupus Warrior T-Shirts and Hoodies.
“Wear” your support. Start conversations. Get others involved.
Click here to order your Lupus Warrior t-shirt and hoodie today!
6