Message from Division Chief Thomas Platts-Mills – May 2020

Our subspecialty has at least three branches which influence our clinics and our research. The primary branch of our practice focuses on traditional allergic diseases, and particularly allergic rhinitis, asthma, and drug allergy. The Division has had a major role in asthma research dating back to 1983, the year our first R01 grant was funded. Over the last ten years, our asthma research has focused on a model using the rhinovirus challenge in allergic patients. This was developed by Dr Peter Heymann, who has recently retired after playing a central role in our division for over 35 years. This year, he published an important paper on the role of the model to investigate the effects of an anti-IgE therapy on symptoms and immune parameters associated with rhinovirus infection. The model also provided information about the immune response to the virus which extended out to 21 days. In addition, Lindsey Muehling and Dr Judith Woodfolk have just published a detailed study on T-cell responses to the virus. Both papers are in the Journal of Allergy and Clinical Immunology (JACI) current Impact factor 14.4. An important part of the funding of the division’s research comes from two U01 grants to investigate the responses to rhinovirus: Pl’s Dr Woodfolk and Dr Larry Borish.

The second major area of focus centers on the expansion of the divisional, clinical, and academic practice related to the investigation of Immune Deficiency Cases. This includes both adult and pediatric clinics, and Dr Monica Lawrence plays an important role in both. In the adult clinics, Dr Borish is a vital team member, while both Jonathan Hemler, MD, and Samantha Minnicozzi, MD are involved in pediatric immune deficiency. Our immunodeficiency program achieved a major milestone last year with recognition by the Jeffrey Modell Foundation. With a rapid increase in our understanding of the genetic basis of primary immunodeficiencis, we also have advocates for dividing the cases between immune-deficiency and other forms of allergy. The important thing is that the subspecialty is developing both in research and clinically and it appears likely to continue changing and expanding.

The third major branch of the subspecialty today relates to food allergy. The well-established immediate reactions which are dominant in children, being food allergens such as peanut, egg, tree nut and milk, all of which have increased dramatically over the last 20 years. More significant to the Division’s research are two forms of food allergy that are not manifest immediately following exposure and have both appeared since 1990. These two forms are eosinophilic esophagitis (EoE) and delayed anaphylaxis to red meat, also known as the alpha-gal syndrome (AGS). Dr Emily McGowan has established successfully combined clinics in EoE with Dr Bryan Sauer in adult gastroenterology and Dr Barrett Barnes in pediatric gastroenterology. Together, they have enrolled over 250 subjects with EoE, and that research is currently funded by two R-21 grants. There are multiple aspects to this research, which focuses on understanding the etiology and management of the disease. An important part of the research relates to understanding the relevance of IgG4 antibody response to milk and wheat proteins. In this respect, Dr Rung Chi Li has been investigating the nature of the IgG4 deposits that are found in the esophageal biopsies.

The cases of alpha-gal syndrome (AGS) have continued to appear in our clinics. However, there have been some new forms of clinical presentation (See T. Platts-Mills et al JACI in Practice 2020). A major aim of the current funding of the R-37 was to understand the geographic distribution of cases of AGS. We have recently completed a national survey of the syndrome, which provides additional evidence that alpha-gal cases overlap with the territory of the lone star tick. A large number of cases have been reported in the Southeast, but cases have also presented in areas of the Midwest and Coastal Atlantic. The primary factor is clearly the relationship to the lone star tick and its primary breeding host, the deer on our lawns. Additionally, we have demonstrated a strong negative correlation between both the geographic distribution of the imported fire ant and cases of fire ant anaphylaxis and the number of cases of AGS seen by regional allergists. The work has relied heavily on the geospatial mapping skills of Behnam Keshavarz, PhD, and Dr Jeffrey Wilson has also played a major role. Our manuscript on this distribution has recently been reviewed, and we are currently revising it for JACI. The important element of the results is two-fold: 1) it is possible to predict that the area where the syndrome is common will continue to move north with climate change, and 2) that cases in the south will probably be decreased by ecological competition between the tick and the imported fire ant. We also have several ongoing collaborations to further understand the putative connection between alpha-gal and cardiovascular disease. This includes projects with our UVA colleagues Dr Coleen McNamara and Dr Angela Taylor in the cardiology group and Dr Robert Hawkins in cardiothoracic surgery. In addition, we have become increasingly aware of the significance of abdominal symptoms in patients with AGS. In some cases this includes severe G.I. pain as a feature of anaphylaxis, in other cases, the symptoms are easily confused with irritable bowel syndrome (IBS). In this respect, we have recently started a collaboration with local G.I. providers to carry out an investigation of alpha-gal syndrome presenting as IBS.

Shifting away from our research endeavors, our clinical practice has flourished during this past academic year, at least up to March! The clinical practice is led by Dr Timothy Kyin and Dr Anna Smith. Our entire Division is now learning how to run clinics by phone or E-mail. Fortunately, there are many aspects of outpatient medicine that can be handled by telephone or Telemedicine. We are all especially grateful to the dedicated nurses and staff who run the clinic. Their willingness and ability handle so many of the questions raised by our patients, and the countless hurdles to cross, as we work through this unprecedented situation together, stand as a testament to our Division’s strength. And, I want to personally acknowledge all the dedicated and professional members of our Division not previously mentioned: our lab support staff, (without whom we would not be able to undertake our valuable research), our administrative and fiscal support team, our grants and clinical trial support team, our dedicated team of Fellows, and all of my fellow clinical and research faculty in the Division. ~ Thomas AE Platts-Mills, MD

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