Identifying the Unknown Contributors to Shellfish Allergies

According to a 2004 study in the Journal of Allergy and Clinical Immunology, seafood allergies are reportedly present in 2.3% of the general population, or approximately 6.6 million Americans (Sicherer, Munoz-Furlong, and Sampson, 2004).  This represents a serious health concern for the U.S.  With seafood – notably shellfish – consumption having risen in popularity and frequency globally, it has become pertinent that shellfish allergies become better characterized (NOAA, 2013).

     The manifestation of shellfish allergies can be highly variable with symptoms ranging from hives, tingling or swelling of the lips, tongue or throat, chest tightness, shortness of breath or difficulty breathing, nausea and vomiting, to full-blown anaphylaxis (Cleveland Clinic,2012). The allergens associated with shellfish allergies are not well characterized and thus management of such an allergy is often simply limited to avoidance or dietary elimination of shellfish.   Additionally, treatment is restricted to emergency care following exposure (Lieberman et al.,2010). So far, it is known that there are heat stable antigens within shellfish that bind to human IgE, an immunoglobulin or antibody that likely originally evolved as a defense against internal parasites such as helminthes and now significantly contributes to immune-mediated hypersensitivity reactions. Once bound to an allergen, IgE initiates intracellular signaling, leading to the degranulation of immune cells. Degranulation is the release of antimicrobial cytotoxic molecules and mediators of inflammation, which in this case eventually leads to the previously described symptoms. One major type of shrimp allergen that has been identified is tropomyosin, a protein associated with the thin filaments in muscle cells and microfilaments in non-muscle cells. However, there are many other IgE reactive shellfish proteins that have yet to be identified

     A recent study published in PLOS One sought to identify and study different IgE-reactive components of commonly eaten shellfish.  The investigators primarily sought to compare the IgE reactivity of raw and heated proteins of the blue swimmer crab and the black tiger prawn. By treating whole blood and blood sera of individuals with and without shellfish allergies with raw and cooked shellfish extracts, investigators were able to quantifiably measure the degree to which IgE reactivity occurred in response to treatment and to identify unique IgE reactive proteins.

NKD2G and Allergic Inflammation

It seems to me that almost everybody nowadays has either a food allergy, seasonal allergy, or both.  Therefore, it becomes more important to understand the mechanism of allergies so that we can better treat them.  This paper examined the effect of the natural killer (NK) cell receptor NKD2G on pulmonary inflammation caused by allergic reactions. 

Allergies are a type of type 1 immune hypersensitivity (HS1).  There are two stages of HS1: sensitization and effector.  During the sensitization stage, the allergen is gathered by dendritic cells which move to the lymph node where they present the allergen to naïve Th cells.  These Th cells then provide T-cell help to B cells which release homing cytokines for other leukocytes to follow.  Other immune cells produce IL-4, IL-5 and IL-13 which facilitate isotype switching to IgE antibodies.  These antibodies then bind to receptors on the surface of basophils and mast cells.  The effector stage is the second exposure to the allergen.  The IgE antibodies bound to mast cells recognize the allergen and cause degranulation of the mast cells which have different effects depending on the tissue in which this is occurring.¹

This video might help you understand immune hypersensitivity better as well:

The first experiment performed examined how NKG2D regulated the pulmonary inflammation caused by house dust mites (HDM).  HDM extract was given to mice that lacked the NKG2D receptor (klrkl^-/-) and compared to those that had the receptor (klrkl^+/+).  As a result, klrkl^-/- mice showed a greatly reduced inflammatory response when compared to klrkl^+/+ mice.  Additionally, there was less protein exudate in the airway when measured in the bronchoalveolar lavage (BAL) and significantly diminished recruitment of neutrophils, eosinophils and lymphocytes  in klrkl^-/- mice.  Furthermore, of the CD4+ T cells that were recruited in klrkl^-/- mice, much less IL-4 and IL-13 was secreted proportionally when compared to klrkl^+/+mice.² 

Can Antibiotic Exposure Influence Development of Allergic Diseases?

A recent study provides certain implications for an association between exposure to antibiotics at a young age and the development of allergic diseases, primarily asthma, in early childhood.¹

            At some point, most people have gone to the doctor’s office and left with a prescription for an antibiotic. In today’s world, antibiotics have developed a connotation as a medicine that can ward off all sorts of sicknesses, which is only partially true. What many people don’t realize is that antibiotics are strictly useful for fighting bacterial infections and will have no effect on viral illnesses.* Although antibiotics have saved countless lives since the discovery of penicillin, there are some concerns about their use.

There two main negative consequences of using antibiotics more liberally than in the past: some unhealthy bacteria have increased resistance to treatment and administration of antibiotics can lead to decreased levels of healthy bacteria. The first consequence relates to overprescribing antibiotics for patients that may not be suffering from a bacterial infection. Every time a person takes antibiotics, he or she increases the likelihood that bacteria in the body will become resistant, which makes it difficult to treat later infections.^#

Commensal Bacteria

The second consequence, which directly relates to the study in question, has to do with the healthy bacteria that reside in the human gastrointestinal tract. When antibiotics are introduced to the body during infancy, a critical period for the development of the immune system, disruption to gut microflora can occur.¹ This could possibly predispose patients to the development of an allergic phenotype. Research shows that disruptions in the normal growth of gastrointestinal bacteria can prevent regulatory T cells from properly dampening the immune system’s response to respiratory allergens.^$  For more information, click here. Reduced diversity of microbes in infant excrement has also been connected to an increased risk of allergic diseases late in childhood.²

Allergic diseases develop when a person's immune system becomes sensitized to a normally harmless antigen. Type I hypersensitivity is a category of allergic reaction in which CD4+ Th2 cells that interact with these antigens stimulate B-cells to produce Immunoglobulin E (IgE) antibodies. These antibodies will then mark the specific antigen for destruction by other immune cells.⁺ Once the individual has been initially exposed and developed the specific antibodies, a subsequent exposure to the allergen will result in an allergic reaction. For more information, click here.

Mechanisms of Allergic Response