Method Discovered for Reversing Bone Loss and Inflammation in Immune Disorder

People who suffer from leukocyte adhesion deficiency, or LAD, are vulnerable to severe oral infections such as periodontitis and are likely to lose their teeth at a young age.  However, researchers from the University of Pennsylvania School of Dental Medicine along with investigators from the National Institutes of Health have discovered a method for reversing bone loss and inflammation from periodontitis in patients with LAD.

The results of the research which was led by Penn Dental Medicine’s George Hajishengallis, professor in the Department of Microbiology in collaboration with Niki Moutsopoulos of the National Institute of Dental and Craniofacial Research was published in Science Translational Medicine.

What is LAD

Leukocyte adhesion deficiency, or LAD, is a rare, life-threatening disease in which the immune system is missing the molecule neutrophils which is needed by immune cells to fight off bacterial infections.  The accepted belief was that LAD patients are vulnerable to severe gum disease because neutrophils is unable to cross the bloodstream to reach the gum tissue, allowing bacteria to thrive in the gums.  However, the research from this study challenges this belief.

Difference in LAD Patients

The researchers under Hajishengallis and Moutsopoulos noticed that gum disease and bone loss continued to occur in LAD patients after being treated with antibiotics or having their plaque removed.  While these patients did have a lack of neutrophils present in their gum tissue, which was expected, they also showed an abundance of bacteria on the surface of their teeth with normal bacteria levels within their gum tissues.

“This is a very different form of periodontitis than we see in otherwise healthy people, in which the neutrophils can cause disease by being too active or present at high numbers in the gums,” according to Hajishengallis.

The researchers compared instances of periodontitis in LAD patients and otherwise healthy patients to discover what makes the gum disease unique in LAD patients.  They noticed that people with LAD had high levels of the molecule IL-17 mRNA and IL-17 expressing cells in their gums.  The IL-17 molecule acts as a signaling pathway and when it senses that infected tissues are low on neutrophils, the level of IL-17 increases to encourage the production and migration of neutrophils to the infection.  But because neutropils cannot leave the bloodstream in patients with LAD, the inflated IL-17 levels just lead to inflammation, and the development of osteoclasts that break down bone.

“We suspected that the bone loss was occurring because of IL-17 and not because the neutrophils could not control the bacterial infection,” says Hajishengallis.

Research in Mice

The researchers injected mice that have been bred with an LAD like disease with molecules that block IL-17 activity in the gums to determine if IL-17 is the cause of periodontitis and bone loss.  They discovered that by blocking IL-17, they were able to inhibit inflammation and bone loss as well as bacterial overgrowth.  According to Hajishengallis, “This is not as strange as it might sound.  Periodontal bacteria thrive on inflammation.  Consuming the breakdown products of tissues is how they get their food.  So if you inhibit inflammation you starve them.”

The authors believe that according to their results, bacterial numbers are high in patients with LAD due to the immune system’s abnormal response to normal bacteria levels in the gums as opposed to a defect in the surveillance mechanism of the immune system.  Certain autoimmune diseases such as psoriasis and rheumatoid arthritis are already treated with molecules that inhibit IL-17 activity and the researchers hope that these compounds can also help treat LAD patients with gum disease.

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