Fibrin Buildup in the Gums Contributes to Periodontitis

Research published in Science last week found that buildup of fibrin triggers an overactive immune response that damages the gums and underlying bone, and that suppressing abnormal fibrin activity could hold promise for preventing or treating periodontal disease, as well as other inflammatory disorders marked by fibrin buildup, including arthritis and multiple sclerosis.

At sites of injury or inflammation, fibrin normally plays a protective role, helping to form blood clots and activating immune cells to fight infection. But too much fibrin has been linked with health problems, including a rare form of periodontitis due to a condition called plasminogen (PLG) deficiency. In affected people, mutations in the PLG gene lead to fibrin buildup and disease at various body sites, including the mouth.

To explore the connection between abnormal fibrin buildup and periodontitis, the team studied PLG deficiency in mice and analyzed human genetic data. Like humans with the condition, PLG-deficient mice developed periodontitis, including periodontal bone loss and elevated levels of fibrin in the gums. The mice’s gums were crowded with neutrophils, which are also found at high levels in common forms of periodontitis.

Neutrophils typically defend the oral cavity from harmful microbes. But an excessive neutrophil response is thought to cause tissue damage. To find out if fibrin was driving this overactive response, the researchers impaired its ability to interact with protein receptors on neutrophils. The weakened binding between fibrin and neutrophils completely prevented periodontal bone loss in PLG-deficient mice. Strikingly, it also reduced bone loss in normal mice with a common, age-related form of periodontitis, suggesting that similar mechanisms were at play in both forms of the disease.

“This study suggests that fibrin can cause neutrophil immunity to shift from protective to damaging in certain circumstances,” said senior author Niki Moutsopoulos. “This fibrin-neutrophil engagement may be a driver of periodontitis.”

A genetic analysis of over 1,000 people seemed to support the animal findings. Even in the absence of PLG deficiency, variations in the PLG gene were linked to an increased risk of severe periodontitis, consistent with the idea that similar processes contribute to rare and common forms of the disease.

Taken together, the study suggests that excessive buildup of fibrin in the gums—whether due to changes in genes like PLG, chronic inflammation from a bacterial infection, or some combination of the two—triggers an elevated and ultimately harmful neutrophil response that causes periodontal disease.