Platts-Mills TAE, MacCallum MH, Wilson JM, Workman LJ, Erwin EA
Frontiers in allergy •
From the earliest days of studying the reagins in allergic sera that give rise to the Prausnitz-Kuestner reaction, there was evidence that there were other types of antibodies (Ab) specific for allergens, particularly those induced by immunotherapy. By 1980, not only was IgE recognized and could be measured, but the presence of other isotypes including IgG and IgA in patients with IgE was well established. From that time onwards the development of monoclonal antibodies made it possible to distinguish and measure antibodies of other isotypes such as IgG4, IgG2, and IgG3. Over the past 40 years two things have dominated the field- firstly, the techniques for measuring isotype specific antibodies to allergens have improved steadily. Secondly, several different allergic diseases or phenomena have been identified in which isotype diversity of the antibodies has become a major issue. Prior to 1990 only occasional cases of eosinophilic esophagitis (EoE) had been identified, but since then they have become common. Most of the cases have positive skin tests and/or IgE Ab to cow's milk or wheat, but it became obvious that most cases of EoE are not primarily related to IgE. Today it is clear that IgG4 Ab to these allergens play a significant role in cases of EoE. In 2000 the first reports of children developing tolerance to cat allergen appeared. Today it is clear that this tolerance depends on high levels of IgG4 antibodies and there is increasing evidence that the IgG4 response is primarily against . The most recent novel allergic disease is the alpha-gal syndrome (AGS). This condition is based on IgE antibodies specific for the oligosaccharide galactose alpha,1-3-galactose, which are primarily induced by tick bites. However, in this case it was already well known that all immunocompetent primates have made IgG and IgM antibodies to this oligosaccharide. Furthermore, it is not clear whether the IgG isotypes, particularly IgG1 and IgG3, play a role in the inflammatory response to the oligosaccharide. Overall, it is clear that current and future investigation of allergic diseases requires careful assessment of allergen specific antibodies of diverse isotypes in addition to IgE.
Platts-Mills TAE, Schuyler AJ, Erwin EA, Commins SP, Woodfolk JA
The Journal of allergy and clinical immunology •
Traditionally, the concept of allergy implied an abnormal response to an otherwise benign agent (eg, pollen or food), with an easily identifiable relationship between exposure and disease. However, there are syndromes in which the relationship between exposure to the relevant allergen and the "allergic" disease is not clear. In these cases the presence of specific IgE antibodies can play an important role in identifying the relevant allergen and provide a guide to therapy. Good examples include chronic asthma and exposure to perennial indoor allergens and asthma related to fungal infection. Finally, we are increasingly aware of forms of food allergy in which the relationship between exposure and the disease is delayed by 3 to 6 hours or longer. Three forms of food allergy with distinct clinical features are now well recognized. These are (1) anaphylactic sensitivity to peanut, (2) eosinophilic esophagitis related to cow's milk, and (3) delayed anaphylaxis to red meat. In these syndromes the immunology of the response is dramatically different. Peanut and galactose α-1,3-galactose (alpha-gal) are characterized by high- or very high-titer IgE antibodies for Ara h 2 and alpha-gal, respectively. By contrast, eosinophilic esophagitis is characterized by low levels of IgE specific for milk proteins with high- or very high-titer IgG4 to the same proteins. The recent finding is that patients with alpha-gal syndrome do not have detectable IgG4 to the oligosaccharide. Thus the serum results not only identify relevant antigens but also provide a guide to the nature of the immune response.
The objective is to discuss recent progress in our understanding of the role of the indoor environment in asthma, focusing on the special role of cat allergens. Sensitization to Fel d 1 is the dominant event in inhalant responses to cat; however, there are also IgE responses to the lipocalin (Fel d 4), to cat albumin (Fel d 2), and to the oligosaccharide galactose-alpha-1,3-galactose (alpha-gal) on cat IgA (Fel d 5w) and other molecules. The dose response and routes of sensitization for these allergens are now thought to be diverse. It is important to remember that exposure outside a house with a cat is sufficient to cause sensitization. Furthermore, the only solid evidence about a role in asthma relates to Fel d 1. Recently, it has been shown that tolerance associated with early exposure to cats can persist to age 18 and that IgE to alpha-gal (on cat IgA) is not related to asthma. In addition, a recent study of anti-IgE reinforces the evidence that IgE antibodies to indoor allergens make a major contribution to asthma severity. Exposure to Fel d 1 in a home with a cat is far higher than the levels necessary to induce an allergic (IgE antibody) response. In keeping with that, children may develop tolerance, which can be long-lived. In addition, there is increasing evidence that IgE antibodies to an inhalant allergen, such as Fel d 1, dust mite, or cockroach, are causally related to lung inflammation and asthma.
