The best defense… is a good inflammatory response
For 16-year-old Allen Grimes of Hopkinsville, Ky., a rare genetic disorder that results in an insufficient inflammatory response has left him nearly defenseless against infections.
When he was three weeks old, Allen was diagnosed with chronic granulomatous disease (CGD), a condition caused by a defective enzyme in his phagocytes, infection-fighting white blood cells. The enzyme helps phagocytes produce toxic chemicals like hydrogen peroxide and bleach that kill bacteria. Without it, CGD patients are plagued with recurrent, often life-threatening infections.
To help his body compensate for this deficiency, Allen takes an antibiotic, an anti-fungal drug and gamma-interferon to bolster his immune system. He also avoids situations that could expose him to harmful bacteria and fungi.
Because crops grown in his rural community are rife with molds and fungi, “I can’t work on a farm, which is something I always wanted to do,” Allen says. He also can’t have pets, swim in area lakes or be out in the sun because of his illness and the medications he takes.
But that hasn’t kept him from participating in Little League, band and now varsity football. His family and doctors have always encouraged his active lifestyle. “We think it’s the best way to keep him healthy,” says his mother, Deanna Grimes.
Before the 1970s, CGD was known as “fatal granulomatous disease of childhood,” according to John I. Gallin, M.D., director of the Clinical Center at the National Institutes of Health. Two percent of CGD patients died each year.
Fortunately, by the time Allen was born, Gallin and other researchers had determined the underlying genetic defect and how to treat it. Studies of prophylactic antibiotic therapy in CGD patients in the early 1970s were the first major step. “Low doses of antibiotics reduced life-threatening infections from one (per patient) every year to about one every four years,” Gallin says.
Studies of gamma-interferon yielded an even more dramatic effect—a 70-percent reduction in the number of infections.
In an apparent paradox, CGD patients often form areas of chronic inflammation called granulomas that can lead to life-threatening blockages in the esophagus, digestive system, urinary tract and lungs. Gallin, who has studied CGD and related disorders for more than 30 years, describes the disease as “one of the great examples of the good and the bad that can come of inflammation.”
Bone marrow transplants can cure the disease, but are limited by matching donors. Replacing the defective gene through gene therapy showed some early potential, but the recovery was short-lived. Researchers led by Harry Malech, M.D., chief of the Laboratory of Host Defenses at the National Institute of Allergy and Infectious Diseases, are now looking for new viral vectors that will deliver the normal gene to patients’ blood stem cells more effectively.
With an incidence of only about one or two cases per million people, why have researchers spent so much time studying CGD? “I believe that if you can understand how inflammation is dysregulated in CGD, you might be able to determine the mechanisms involved in other chronic inflammatory diseases like atherosclerosis, Crohn’s disease, arthritis and certain types of cancer,” Gallin says.
Allen and his family chalk up his current good health to a little luck, a strong faith in God and constant vigilance against infection. They also are strong supporters of research.
Allen has participated in some of the treatment studies, and he hopes for a day without needles, pills or I.V.s. A day when he can swim without worrying about getting sick. A day when he can stand in the sun.
“He’ll do whatever it takes to bring awareness to the disease, and to help find a cure,” his mother says.