IMMUNOTHERAPY (Isaac Bromberg)
Immunotherapy is a preventative treatment for sufferers of both localized and systemic anaphylaxis. Usually, allergen is administered via injection in gradually increasing doses, up to a set level, after which a fixed maintenance dose is continued. In some trials and treatments, the initial doses increase rapidly over a number of hours or days. This is known as 'rush' immunotherapy. Individuals treated with immunotherapy show decreased sensitivity to allergens with long term effectiveness (up to 18 months after treatment). (1)
Studies using various allergens show definite changes in immune system response after immunotherapy treatment. After a rush insect venom immunotherapy trial, in addition to a decrease in response to venom challenge, treated individuals responded with a decrease in IL-4 production and an increase in IFN-gamma production (among other changes) indicating a shift in cytokine production from a TH2 to a TH1 distribution. (2) Experiments using dust mite antigen also describe an increase in IFN-gamma production. (3) Some studies show a decrease in both INF-gamma and IL-4, however, and some describe subjective improvements, but no changes in immune-active components. (4, 5)
Because some individuals undergoing immunotherapy suffer from severe systemic anaphylactic reactions, it is possible for the therapy to in fact precipitate an untoward effect. In most cases, persons going through immunotherapy (especially rush protocols) are closely monitored to ensure that they tolerate the antigen. The safety of rush immunotherapy has been demonstrated for a variety of antigens which cause a range of reactions. (6)
Studies investigating new allergen delivery approaches have had mixed results. An attempt to evaluate sublingual (SL) administration of allergen as compared to subcutaneous injection, which is the most common route, showed no immunological response to the SL administration. However, patients treated this way reported feeling less allergy symptoms and lower use of medications. (7)
Another interesting trial investigated the effect of active culture yogurt on symptoms of individuals suffering from allergic asthma. The only noticeable effect of this 'therapy' was a nominal increase in IFN-gamma production by lymphocytes stimulated with concanvalin-A (a mitogenic lectin). Treated individuals reported no change in symptoms. (8)
An evaluation of the use of peanut extract in immunotherapy treatments for individuals with immediate hypersensitivity reactions to ingested peanuts showed increased tolerance to the allergen after a course of rush injections followed by maintenance doses. Unfortunately, nearly all individuals involved suffered from repeated systemic reactions to the treatment. The investigators in this trial feel that the development of a modified peanut extract is necessary before further study is undertaken. (9)
ARE VACCINES THE KEY TO WINNING THE BATTLE AGAINST ALLERGIES AND ASTHMA?
Allergies and asthma afflict numerous people throughout the world. The incidence of allergy and asthma cases has been steadily increasing over the past few years. For this reason many researchers and patients sense the vital necessity to bring relief to the millions who suffer. As a result, scientists are progressing towards the development of vaccines against allergies and asthma.
One study at the University of Uppsala is focused on vaccinating against IgE, the immunoglobulin responsible for allergies and asthma. Researchers hope to reduce the levels of IgE production. A fusion protein was made that contained the constant domains two and three of rat IgE fused to an E. coli protein. When this fusion protein was injected into rats along with an adjuvant, a strong autoimmune anti-IgE response formed. Furthermore, when injected into rats sensitized to ovalbumin, serum IgE levels dramatically diminished. Also, histamine was not released from mast cells and basophils when later challenged by an allergen. However, the researchers discovered an obstacle to conquer, rats with very high IgE levels had an inadequate autoimmune response to the vaccinations. The vaccine's reliability is dependent upon the levels of IgE before the vaccination (1). Another study involves DNA immunization. An allergen gene from a house dust mite was placed into a vector and introduced into mice. IgG antibodies were formed as a response, but not IgE. This meant that IgE responses to IgE specific allergens may be suppressed (2). Also, another experiment showed immunization of mice with plasmid DNA inhibited IgE antibody formation. It was concluded that the CD4+ and CD8+ T cells from these immunized mice induced a T helper one response. This influenced the T helper two response and also down-regulated IgE formation (3, 4).
In addition, peptide vaccines are making big waves on the allergy and asthma research frontier. A peptide vaccine is a small piece of protein from an allergen that is injected into the patient. Such allergens are, grasses, dust mites, and ragweed (5). One such vaccine is ALLERVAX Ragweed, produced by the Immunologic Corporation in Massachusetts. It was shown to lessen ragweed allergy symptoms and reduce patient's use of allergy medication (6). Development of monoclonal antibodies specific for IgE is another line of research scientists are advancing towards. This monoclonal antibody will bind to the Fc portion of IgE and inhibit it from binding and activating mast cells. Through use of this monoclonal antibody more allergen was needed to stimulate an asthmatic response (7). Along similar lines, scientists have made a connection between viral infections and allergies and asthma. It appears that weak infections can stimulate the production of IgE. One such virus is the influenza virus. Therefore, researchers believe that vaccines to these viruses could be a way to stop the over production of IgE (8,9) These research focuses all show tremendous promise. The development of an allergy and asthma vaccine would ease millions from their relentless suffering.
HOW DANGEROUS IS THIS LATEX ALLERGEN?
It was not until the late 1970's, that Latex was recognized as an allergen. Latex allergy can be extremely dangerous and sometimes lethal. Between 1988-1992, the U.S. (CDC) reported approximately one thousand cases of anaphylactic shock and twelve deaths due to latex exposure in hospitals. Nine deaths occurred in patients that were getting a barium enema using a latex stomach tube. (1)
WHO IS MOST PRONE TO DEVELOPING A LATEX ALLERGY?
The majority of the latex exposure comes from use of latex gloves in medical and dental establishments. According to the FDA, persons in the dental profession are said to have the highest risk factors for developing latex allergy. (2)
WHAT IS THIS ALLERGY ALL ABOUT?
Latex comes from the Hevia brazilienzis rubber tree. Latex causes an IgE-mediated allergic reaction. Actually, the allergic reaction is in response to "the proteins which are bound to the isoprene molecules that are responsible for its remarkable elasticity." (3) Early symptoms to this allergy, include hand rashes, dry and cracked skin, nasal congestion, sneezing, and red, watery eyes. Sometimes, asthmatic symptoms can occur, such as wheezing.
The extra powder found on the latex gloves can even serve as a transport of the residual latex proteins that are processing chemicals and endotoxins. As the gloves are being put on or taken off, the powder can be released into the air and easily inhaled. Exposure to latex may also occur through the mucous membranes, for example, during a dental procedure. (4)
IS THERE A WAY TO FIND OUT IF YOU HAVE AN ALLERGY TO LATEX?
In order to detect this unusual allergy, immunological tests have been used. A common enzyme-linked-assay, (ELISA), is used to detect specific IgE to latex. This assay involves the use of an enzyme-labeled anti-IgE and substrate, o-phenyldiamine.
A recent study done by researchers affiliated with the National Cooperative Inner-City Asthma Study found higher incidence of asthma among inner-city children upon exposure to cockroach allergen. The study involved data from eight different inner-city areas from across the country taken from families that were deemed socioeconomic minorities. Factors taken into consideration for the study were family history of asthma, number of asthma related hospitalizations and doctor visits over the course of one year, and the effect of cat and dust mite allergen in the environment of the patients in comparison to cockroach allergen.
Results from the study showed that 50% of the living areas researched(i.e. bedrooms) contained high levels of cockroach allergen. According to the study, a high level of cockroach allergen was that accounting for 85% of the total allergen level measured in the room. In these cases the levels of cat allergen and dust mite allergen were negligible, particularly since the subjects had been skin tested for hypersensitivity to the cockroach allergen. These children had a higher incidence of asthma related hospitalizations and doctor visits compared to other children in the study not exposed to these levels of allergen.
The allergen content in the study was determined from dust collected from the bed linings and carpet, using a monoclonal antibody based ELISA. Skin tests were administered to determine hypersensitvity to each of the three allergens used in the study. (1)
One study has determined the allergic component of the cockroach allergen to be a 23 kiloDalton protein which is a glutathione S-transferase protein of Blatella germanica. The allergen was purified from cockroach body extracts and expressed as a recombinant protein in E. coli using a plasmid vector. The recombinant protein was used in skin tests on patients allergic to cockroach allergen and showed positive tests with allergen concentrations as low as 3 pg. The experimental results from this study also concluded that glutathione S-transferase caused an IgE response and is instrumental in causing asthma in patients allergic to cockroach allergen. (2)
Another study done by Matthias Wjst in Germany focused on discovering the genes responsible for causing asthma. This study looked at gene families that would be good candidates for causing the disease by looking at microsatellites, which are polymorphic gene markers associated with gene families. These markers help to determine the location of a gene that is potentially responsible for causing disease. In his study, Wjst implicates certain genes involved in allergic reaction as those which might be involved in causing asthma. Among these genes are IL-4, FceRIb, TCRa, and HLA DR I. In the case of an allergic reaction, the allergens will be presented by Class II MHC to the TCR on the T helper cell. This interaction will signal the cascade of events leading to the production of IL-4 by the T lymphocyte which in turn will increase the expression of IgE by B cells due to the induction of class switching from the cytokine. (3)
According to Malcom Ritter, a science writer of the Associated Press, researchers have identified six locations on human DNA with which asthma genes may be linked. Two of the locations have been located in past studies, however none of these spots may be proven to hold asthma genes for another three to five years and they are likely not the only places where the genes will be found. Genetic signposts, or markers that are "inherited along with a particular trait [allergic asthma, in this case]" of 80 Australian families were studied in order to determine where to search on the DNA. (1)
INHERITED DESENSITIZATION TO ASTHMA DRUG
Treatment of asthma currently depends on a class of drugs known as beta2-adenoreceptor antagonists (beta2 agonists). This drug enlarges the patient's airways by binding to protein receptors in the lungs, allowing easier passage of air. However, desensitization may occur when continuous exposure to the drug decreases its effectiveness. Researchers have discovered that inheritance may play a key role in quick desensitization of some individuals. Primarily variants of airway receptor proteins which differ in their 16th amino acid were closely studied. Patients who were homozygous (their proteins contained two of the same amino acids, rather than two different ones -- heterozygous) for glycine (Gly 16 / Gly 16) displayed greater desensitization to beta2 agonists than those who were homozygous for arginine (Arg 16 / Arg 16). (2)
CONNECTION BETWEEN BRONCHIAL HYPERRESPONSIVENESS AND IgE REGULATION
A site on the chromosome 5q31-q33 which has shown to influence bronchial hyperresponsiveness, constriction of the airways in response to allergens, and a key factor to identifying at-risk asthma patients was determined to be inherited. This gene is also involved in the total IgE (immunoglobulin E) regulation in serum, and regulation of other cells involved in the allergic immune response. (3)
Isaac Bromberg
bromberg@javanet.com