Researchers find molecules that might mark elusive syndrome.
Amy Maxmen
Ticks spread the bacterium behind Lyme disease - but symptoms can
persist even when the bug seems to have gone.Medical-on-Line/Alamy
Some patients with Lyme disease still show symptoms long after their
treatment has finished. Now proteins have been discovered that set
these people apart from those who are easily cured.
People who experience the symptoms of Lyme disease, which include
fatigue, soreness and memory or concentration loss, after treatment
for the disorder are sometimes diagnosed as having chronic Lyme
disease or post-Lyme disease syndrome. But these diagnoses are
difficult to make, because the individuals no longer seem to harbour
the bacteria that cause Lyme disease. And the symptoms could instead
be indicative of chronic fatigue syndrome or depression.
Now Armin Alaedini at Weill Cornell Medical College in New York and
his colleagues have found that patients diagnosed with post-Lyme
disease syndrome have antibodies that suggest they carried the
infection for an unusually long time. The finding, published in
Clinical Immunology1, might help the syndrome to be better understood,
diagnosed and treated.
Alaedini's team looked at antibodies made in response to a protein
called VlsE, which is found on the surface of Borrelia burgdorferi,
the tick-borne bacterium that causes Lyme disease.
The antibodies recognize a snippet of the protein called an epitope,
and recruit the immune system to attack the bacterium. The researchers
found that post-Lyme sufferers have a greater variety of antibodies to
this epitope than patients whose infection cleared up quickly.
This finding suggests that patients with chronic symptoms have
experienced a prolonged infection, caused by microbes that have evaded
the immune system by varying the epitopes they carry. As a result of
these variations, the body makes new antibodies targeting the modified
protein. The longer the microbe manages to keep changing, the more
diverse its host's antibodies become.
Some post-Lyme sufferers had varied antibodies against VlsE epitopes
despite being diagnosed and treated early, says Alaedini. "That could
mean they naturally have a different antibody response to the
infection than most people; it could mean they weren't treated
properly; or it's possible they were reinfected and the second
infection was never treated," he says.
Inflammatory role
"This is the first study I've seen that shows some immunologic
difference between someone who resolves their Lyme and someone who
develops post-Lyme disease syndrome," says Linda Bockenstedt, a
rheumatologist and immunologist at Yale School of Medicine in New
Haven, Connecticut.
The presence of varied antibodies hints that the chronic symptoms
could be caused by an ongoing inflammatory response caused by
antibodies mistakenly reacting to the body's own proteins, Bockenstedt
suggests.
"The big question to me is whether this can lead to an autoimmune
phenomenon," says Bockenstedt. "But if that were the case, I'd expect
the disease to worsen without immune-modulating treatment, and it
doesn't."
Alaedini suggests that higher levels of antibodies could increase the
body's levels of cytokines, immune-system proteins that can trigger
the symptoms experienced by patients with post-Lyme disease syndrome.
"Various cytokine profiles have been associated with fatigue, anxiety
and depression," he explains.
If these antibodies are unique to people with chronic Lyme disease, it
could lead to a test and treatments for the disorder, Alaedini says.
It could also guide treatment of the disease itself. "If patients with
an acute infection develop antibodies to these epitopes, perhaps they
require a more aggressive course of therapy," he adds.
But a predictive marker won't be useful without new therapies for the
persistent symptoms, says Henry Feder Jr, a physician specializing in
infectious diseases at the University of Connecticut Health Center in
Farmington. If an immune response problem leads to the syndrome,
antibiotics won't help. "I guarantee you that if you tell a patient
they won't feel better after antibiotics, they won't," Feder says. "We
need to know what's going on."
References
Chandra A. et al. Clin. Immunol.
http://dx.doi.org/10.1016/j.clim.2011.06.005 (2011).
http://www.nature.com/news/2011/110805/full/news.2011.463.html
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