Revenge of the Mountain Cedars

If you live in or have friends in Austin or the Texas Hill Country, you likely know about cedar fever, a.k.a. cedar pollinosis. Starting with an itchy nose, scratchy throat, watery eyes, and sniffles, it progresses to congestion, cough, and fatigue. One in five Texans endures this often severe seasonal allergic reaction to the pollen of mountain cedar (Juniperus ashei). From December until March, it sparks misery through a broad swath of the south central United States and northern Mexico.

The allergy is spreading, and research at UTMB may explain why: A new, stronger class of cedar pollen allergens is emerging—apparently triggered by environmental pollution. Terumi Midoro-Horiuti of UTMB’s Child Health Research Center and her UTMB colleagues have isolated, characterized, and cloned mountain cedar allergens that she calls Jun a 1 and Jun a 3—the latter belonging to a family of pathogenesis-related, or PR, proteins. In 2004, UTMB researchers determined the crystal structure of Jun a 1, a potent allergen in its own right. But Midoro-Horiuti finds the possible link between pollution and increased production of Jun a 3 particularly interesting. “We have hypothesized that certain pollutants, including ozone, ultraviolet light, pesticides, and other chemicals, inflict stress on the plants,” Midoro-Horiuti explains, “prompting them to produce these potent proteins, which in turn enhance the allergic immune response in people.”

She and her colleagues, who have published research on cedar fever or presented results to scientific peers about half a dozen times starting with a seminal publication in the Journal of Immunology in 2000, have sampled mountain cedar pollen from various areas in Central Texas and found high concentrations of the Jun a 3 protein in trees near I-35 in Austin. The levels of allergy-causing PR-proteins from trees near the highway, Midoro-Horiuti noted, are considerably higher than those from sampled trees far from I-35.

In her office, Midoro-Horiuti has miniature mountain cedars growing in a terrarium-like chamber where light, temperature, and wind are controlled to simulate outdoor conditions. By subjecting these plants to stressors such as pesticides and ultraviolet light, UTMB researchers have confirmed that these plants, too, produce higher levels of allergy-prompting PR-proteins.

Midoro-Horiuti, who suffers from cedar fever herself, came to UTMB from Japan in 1999 hoping to find the molecular basis of cedar pollen sensitivity so that scientists could develop countermeasures to it. Currently, the main treatments for cedar fever merely aim to alleviate symptoms. (Allergy shots actually desensitize the immune system, but they typically take several years to work, are effective in only about 30 percent of patients, and sometimes cause bad side effects.) The National Institute for Allergy and Infectious Diseases this year awarded UTMB $1.1 million over four years to help develop a vaccine to immunize people against plant allergies the way traditional vaccines work against infectious diseases. Pediatrics professor Randy Goldblum, principal investigator on the grant with Midoro-Horiuti as co-investigator, says the team hopes to begin testing a human vaccine by 2008.

If and when such a vaccine is found, a huge market may await it. After discovering Jun a 3 in mountain cedar trees, the UTMB team—including collaborators in UTMB’s Department of Human Biological Chemistry and Genetics and the Sealy Center for Structural Biology—found that related species within the cedar family cause similar problems worldwide. The researchers calculate that they afflict an estimated 30 percent of the world’s population, or almost 2 billion people. Among them are nearly 64 million people in Midoro-Horiuti’s native Japan, about half that country’s population. —Cathy C. Nall