ALLERGY & IMMUNOLOGY – RESEARCH

DEDICATION CEREMONY FOR PIDD CLINICS HELD

DEDICATION CEREMONY FOR PIDD CLINICS HELD
The Division of Asthma, Allergy and Immunology held the dedication ceremony for the new Adult and Pediatric Primary Immunodeficiency Disease Clinics (PIDD). Drs. Monica Lawrence and Larry Borish worked closely with Vicki and Fred Modell and the Modell Foundation to open these clinics at UVA in 2019.
(Pictured from left are: Vanessa Tenembaum, Duke Dickerson, Fred Modell, Noah Brown, Jeff Kent, Dr Monica Lawrence, Darla Low, Rob Metz, Vicki Modell, Gail Moore, and Dr Larry Borish)

CLINICAL INITIATIVES

In addition to providing comprehensive care for adult patients with the spectrum of allergic disorders and asthma our division has numerous specialized clinical initiatives:

Immune deficienciesThe immunodeficiency clinic is a referral center for patients across the region with known or suspected primary and secondary immunodeficiencies. Patients benefit from a comprehensive approach to their care, including careful review of medical records, evaluation by a clinical immunologist (Dr. Larry Borish and Dr. Monica Lawrence), laboratory, radiology, pathology and/or genetic testing (as indicated), and access to cutting-edge treatments. Patient care is facilitated by a dedicated nurse care coordinator (Darla Low, RN). The clinic receives generous support from the Jeffrey Modell Foundation, which recently designated UVA a Diagnostic and Research Center for Primary Immunodeficiency.

PIDD We have a research program that is currently focused on IgE as a biomarker of humoral immunodeficiency. We also have recently received approval to establish a biorepository which will bank serum, blood and genetic materials from patients with primary immunodeficiency to use in future research.

Dermatology – Both adult and pediatric patients are seen in the combined allergy/immunology/dermatology clinic by Dr. Barrett Zlotoff (dermatology) and Dr. Monica Lawrence (allergy/immunology), who provide multi-disciplinary management of conditions such as severe atopic dermatitis, chronic urticaria, and contact dermatitis.

Food Allergy – We are establishing an extensive network for the diagnosis and management of food allergies including protocols for advanced diagnostic testing and challenges. Patients are also invited as appropriate to participate in many of the novel therapeutic desensitization clinical research protocols currently being developed.

Severe Asthma – In conjunction with Dr. Drew Harris we are now offering a combined allergy/pulmonary clinic devoted to the care of severe very poorly controlled high-risk asthmatics. We have now entered the biologic era of the care of these severe asthmatics with 5 biologics currently approved and several others in various stages of development. Identifying and matching individual patients to the appropriate therapeutic can be quite challenging but when the correct match is achieved this can also be quite rewarding.

Eosinophilic Esophagitis (EoE) – In order to provide integrated care to patients with EoE, we have established a multidisciplinary EoE clinic, which combines the expertise of allergy (Emily McGowan), gastroenterology (Bryan Sauer [adult] and Barrett Barnes [pediatric]), and nutrition. Patients with EoE receive comprehensive care in the diagnosis, treatment, and management of this condition, which includes the opportunities to pursue either medical or dietary therapy and participate in ongoing clinical trials.

Chronic Sinusitis – Chronic sinusitis. Our sinusitis clinics involve combined appointments with members of the allergy division (Drs. Larry Borish and Anna Smith) who work in close collaborations with two colleagues in the Department of Otolaryngology (Drs. Spencer Payne and José Mattos). Patients are thereby offered comprehensive evaluation of anatomical, allergic, and immunologic mechanisms driving their disease, thorough assessments with nasal endoscopy and radiographic analysis followed by team developed medical and surgical individualized protocols. As with all of our other specialty clinics we have a strong research interest including studies regarding pathogenic mechanisms of eosinophilic chronic sinusitis, mechanisms of aspirin-exacerbated respiratory disease, and evaluation of causes of anosmia in these disease. In addition, as appropriate, patients are offered opportunities to participate in clinical trials of the numerous biologic therapies being developed for these disorders.

RESEARCH LAB INTERESTS

Platts-Mills Lab
Alpha-gal
In collaboration with Coleen McNamara and Angela Taylor we have identified a potentially very serious connection between the presence of IgE antibodies to the oligosaccharide galactose alpha-1,3-galactiise (alpha-gal) and coronary artery disease (CAD) (Wilson et al 2018). The hypothesis is that following eating meat derived from mammals the normal slow, i.e. hours, development of LDL and HDL which can be 20-10 nanometers in diameter, there are particles of fat in the circulation carrying alpha-gal epitopes which are small enough to pass through the endothelial wall of blood vessels. This can give rise to urticarial or anaphylactic reactions in the skin and the systemic circulation at 3-6 hours after eating meat. Alternatively these particles could contribute to the development of CAD. Strikingly the association appears to apply to patients who have the IgE antibodies and is not restricted to subjects who experience attacks of hives or anaphylaxis.

The phenomenon of IgE antibodies to alpha-gal that develop following tick bites is almost certainly a persistent feature of rural life and are unlikely to be new. However the prevalence of Lone Star ticks close to houses has undoubtedly increased with the dramatic rise in the population of deer on our lawns. It is important to remember that there were no deer in Albemarle County in 1948 and still very few as late as 1980. The primary cause of the increase in the deer population was the introduction of hidden electronic fences to control dogs, and the deer are a major breeding host for Lone Star ticks. (Gaines et al 2014) This has led to the remarkable fact that for the first time in ten thousand years we have a large population living in suburban areas with wild animals free to approach the homes closely. The question is whether we have created a truly dangerous threat to our health. The associated question is whether this association with antibodies to alpha-gal is a major part of the reasons why a diet based on mammalian products appears to be such an important risk for CAD.

Borish Lab
Rhinovirus-mediated Asthma Exacerbations
The Borish laboratory is currently funded by the NIH and pharmaceuticals to investigate innate immune mechanisms driving rhinovirus (RV)-induced asthma exacerbations. In particular, these studies involve inoculation of volunteers who are either healthy controls, allergic rhinitics, or asthmatics with RV-A16 strain.These studies confirm reduced expression of an interferon-mediated innate immune response in the asthmatics with reduced expression of FNs-a, -ß, and –l reflecting in part reduced expression of the viral RNA signaling machinery MDA-5 and RIG-I. This absence of an IFN-mediated response, however, is compensated by increased expression of a “type 2” (allergic inflammatory) response in the asthmatics reflected by increased expression of the epithelial cytokines IL-25, IL-33, and TSLP, increased recruitment of innate lymphoid cells resulting in increased eosinophilic inflammation. Our current hypothesis is that the enhanced eosinophilic response successfully drives an anti-viral immune response and, as such, the asthmatics display quite similar viral loads in comparison to the healthy controls and allergic rhinitics. However, this is accomplished at the “price” of eosinophil-mediated inflammation, which we suspect contributes to the more severe and protracted symptoms observed in the asthmatics.

Woodfolk Lab
Ongoing research focuses on immune mechanisms of asthma pathogenesis in children and adults. This includes studies on the adaptive response to rhinovirus, which is a major trigger of acute wheezing episodes in children. A key goal is to elucidate the properties of pathogenic T cells in the blood and airways using high-dimensional single-cell analytical methods, and to define mechanisms of T-cell induction. Dr. Woodfolk recently received an NIH/NIAID R21 award to explore the mechanistic link between IgE and Th1 responses in rhinovirus-induced asthma. In an ongoing U01 project (NIH/NIAID), she and her fellow PI, Ronald Turner MD (Department of Pediatrics), are working to define hallmarks of cross-protection in the adaptive response to rhinovirus in a novel sequential challenge model in humans that uses 2 different rhinovirus strains. In a new collaboration with Max Weder, MD, and Michael Shim, MD, in the Division of Pulmonary and Critical Care Medicine, Dr. Woodfolk’s lab is also exploring the features of T-cells that may contribute to lung transplant failure.

Filed Under: Clinical Research, News and Notes, Research

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