Wednesday, June 10, 2015

Hay Fever: Maladies, Melodies And Remedies

TheScope: In addition to kicking off the barbeque, swimming and vacation seasons, spring also marks the beginning of that pesky and sometimes debilitating seasonal woe, hay fever. Much like Noel Coward’s 1924 play Hay Fever, the colloquial designation has really nothing to do with hay or fever. Clinically known as allergic rhinitis, hay fever describes the hypersensitivity to airborne allergens and the onslaught of bothersome symptoms they provoke. Approximately 20% of the world’s population suffers from seasonal or perennial hay fever. Even Paul Simon wasn’t spared from the suffocating spiral that is allergies.

With the blooming of spring flowers and sprouting of fresh green leaves and grasses, we are reminded that life is all around us. Quite literally, too, as windborne plant pollen is small enough to enter our eyes, nose, and mouth. Pollen, the primary cause of seasonal allergies, contains the male gametophytes of seed-bearing grasses and trees. Each pollen grain contains a generative cell, or sperm, which fertilizes the egg of the female plant, and a vegetative cell, which develops into a pollen tube and delivers the sperm to the ovule. Many trees and grasses rely on wind to spread their pollen and fertilize the female plant. So although your college roommate may have been discrete while attempting to procreate, wind-pollinated plants uphold no such personal boundaries.

Next time you smell a flower, realize you are sniffing a plant’s “naughty bits”.

So which plants are responsible for producing the powdered cheese-like substance that coats our houses, bicycles, and cars? Although thousands of plant species produce pollen that makes the Holderness family cough and gag, only a handful are responsible for their allergic wheezing and sneezing.

The exact timing of seasonal allergies can vary depending on region and climate. You can blame your early spring allergies on tree pollen, particularly that from birch trees. From March to May, many other trees including beech, ash, pine, box elder, cottonwood, oak, mulberry, elm, alder, cedar, hazel, willow, poplar, linden, olive, hornbeam, and plane contribute to early spring allergies. By June, grass pollen becomes predominant, especially timothy and ryegrass. Other grasses such as Bermuda, Johnson, Kentucky bluegrass, orchard, redtop, sweet vernal, and rye contribute to allergies. As the heat and humidity rises during July and August, your hair and electricity bill aren’t the only things that grow. Molds can thrive in grass, grains and leaves; airborne spores can cause hay fever.
The warm days and cool nights of late summer and autumn are perfect conditions for weeds, particularly ragweed, which is the primary cause of autumn-onset seasonal allergies. Ragweed can produce metric tons of pollen per square mile of plant. Other weeds that produce allergenic pollen are cocklebur, burning bush, lamb’s quarters, pigweed, plaintain, Russian thistle, sagebrush, mugwort, and sheep sorrel.

The heavy vegetation towards the end of the growing season provides a perfect breeding ground for additional outdoor mold. Mold grows in fallen autumn leaves, hay, and straw, and can be stirred up during raking or baling. In general, mold spores are considered perennial allergens because mold has the potential to grow outdoors and indoors, especially in kitchens, bathrooms, and basements throughout the entire year. However, growth conditions are optimal during different seasons, potentially resulting in a seasonal effect with mold allergies.

Even in winter, mold spores on indoor live pine trees can cause an allergic reaction. So even though the pine tree isn’t releasing pollen, it can still aggravate hay fever symptoms.

Other perennial allergens besides mold spores include dust mites, pet hair dander, and cockroach droppings. Dust mites are always present, but have been shown to increase with installation and use of central heating and insulated windows in apartment buildings. And although we may not even know cockroaches are present, the proteins in their droppings can cause hay fever. Cat dander is the most common cause of pet allergies, but thankfully The Big Bang Theory writers conveniently overlooked Sheldon’s alleged cat dander allergy so he could adopt this zazzy guy.

What is it about allergens that trigger the allergic response? Although scientists have worked to understand the molecular details of allergens and how they interact with components of our immune system, there is no clear answer as to what specifically makes something allergenic. However, within many of the most common allergens, the primary antigen has been identified. The antigen is the specific molecule that is recognized by our immune system. Antigens can be different components of a bacterial cell or viral particle; in the case of allergens, it is a protein derived from pollen, dander, mold, etc.

Pollen from birch trees is one of the largest contributors to hay fever in spring and early summer in North America The primary antigen from birch tree pollen, Betula verrucosa is called Bet v 1. The Bet v 1 antigen exists as a mixture of 14 isoforms that share ≥ 96.5% sequence identity; these isoforms possess different binding capabilities for the antibody immunoglobulin E (IgE). In fact, only 1 of the 14 isoforms, Bet v 1.0101, induces an immune response in an individual with birch tree allergy, and the two other isoforms tested, Bet v 1.0401 and Bet v 1.1001 induced no response (PMID:  20005001). Immune cells isolated from patients with no birch tree allergy did not react to any of the isoforms. The difference in the antigens is their affinity for the IgE, but precisely what makes one antigen more reactive than the other is unclear. On a basic level, the protein sequence and structure influence the binding to antibodies.

Birch pollen primary antigen Bet v 1 (
One complication with diagnosing and treating allergies is the potential for cross-reactivity between different antigens. In some parts of the world, allergic patients are double-sensitized to ragweed and mugwort, Artemisia vulgaris. The flowering season of these two plants overlaps, making it difficult to diagnose the primary sensitizer. In addition to increasing the number of allergies a patient may have, cross-reactivity also complicates prescription of the correct immunotherapy to combat the primary allergy. The primary antigen of mugwort is Art v 1 and up to 95% of people are sensitized to Art v 1. However, a minor mugwort antigen, Art v 6 shares high homology with and commonly cross-reacts with the primary ragweed antigen, Amb a 1. At least 90% of ragweed-allergen sufferers are sensitized to Amb a 1. This means that patients who are allergic to ragweed may be sensitive to mugwort and vice versa. New proteomic technologies allow for more accurate diagnoses of the primary sensitizer so that the proper immunotherapy can be prescribed. Treatment of allergies will be discussed in article 4 of this series.
With so many potential allergens bombarding us more or less year-round, it’s almost surprising that more of us don’t suffer from hay fever. As mentioned above, 1 in 5 people are afflicted and, unfortunately, that number is increasing, particularly in suburban areas of North America. Perhaps the reason allergies are not more common is because they are not hardwired into us, as is the immune response to infectious agents such as bacteria, viruses, and parasites. Hay fever is considered an atopy, a genetic predisposition to mount inappropriate immune responses to harmless environmental allergens. The immune response mounted against allergens will be described in detail in article 2 of this series.
The tendency to have seasonal allergies is hereditary, but does not follow Mendelian principles, like inheritance of eye or hair color. In addition to genes, the environment contributes to allergy susceptibility. Understanding the genetic and environmental factors involved in allergy development is complex and requires sound knowledge of the actual allergic response. A more complete discussion of genetic and environmental factors that influence allergy susceptibility will be presented in the third article of this series. We hope you’ll tune in for the remaining articles in this ongoing series.