Platts-Mills Research

PRIMARY APPOINTMENT:

Professor of Medicine

CONTACT:

UVA Division of Asthma, Allergy, and Clinical Immunology
PO Box 801355
MR-4
Charlottesville, VA

Telephone: 434.924.2227
Fax: 434.244.4503

The Platts-Mills’ lab is long-standing interested in understanding environmental and immunologic contributions to allergic disease. A major focus of the lab has been related to understanding how dust mites and cat allergens are causally related to asthma. More recently, our lab has been a primary driver in understanding a novel form of allergic reaction to red meat (alpha-gal syndrome or AGS) caused by tick bites. In 2018, we published a paper on the relationship between sIgE and alpha-gal, and evidence of coronary artery disease (CAD) samples were obtained by Angela Taylor, MD (UVA Heart and Vascular Center) using intravascular ultrasound (IVUS). In 2022, a major cardiology group in Sydney, Australia, confirmed our results on the positive association between alpha-gal and CAD. Most recently, we saw a woman in her 40s who had been seen initially 8-10 years prior for a severe episode of anaphylaxis and diagnosed with AGS. Just before her recent visit, she had two myocardial infarctions and now has five stents in her main cardiac arteries. Between her initial visit and these cardiac events, she maintained a strict diet, avoiding mammalian meat and organs; however, she continued to consume dairy products derived from Bos domesticus.

Cases like this emphasize two questions: Should all patients or subjects with sIgE to alpha-gal be advised to avoid all mammalian products because of the potential chronic risk of cardiac disease (CAD)? This would include avoiding dairy products even though, in most cases, the products would not give rise to clinically apparent allergic reactions.

The most promising candidate for another marker is antibodies to alpha-gal of the IgG3 isotype. IgG3 is an inflammatory immunoglobulin that has recently been reported to ‘increase after implantation of porcine or bovine aortic valves.’ We are currently adapting the ImmunoCap 250 machine to assay IgG3-specific antibodies using reagents provided by Dr. Robert Moverare from Phadia Thermo-Fisher in Sweden.

Studies on TH2 antibody responses and Asthma
We have recently conducted detailed studies on specific IgE and IgG4 antibodies to component allergens (single proteins) of cat and dust mites in sera from six hundred teenagers participating in the Viva birth cohort in Boston. The primary evidence on these children shows that dust mites and cats are the main sources of asthma-related indoor allergens. However, analysis of the data on the two major allergens Der p 1 and Fel d 1 has revealed a striking difference in IgG4 compared to the responses to more recently identified allergens such as Der p 23, Fel d 4, and Fel d 7. As expected, the primary contributor to specific IgG4 for cat allergens was Fel d 1. However, the surprise is that the other cat allergens show no significant effect on sIgG4 related to living in a home with a cat. The most likely relevant feature of these secondary allergens is that they are present in extracts in significantly lower quantities. The results imply that IgG4 responses require a higher quantitative exposure than IgE responses. In addition, the results suggest that some of the allergens other than Der p 1 and Fel d 1 have greater relevance to asthma because they induce less IgG4 relative to IgE antibodies.