ASTHMA AND ALLERGIC DISEASES CENTER

Summary

Principal Investigator: Thomas Platts Mills
Abstract: The Asthma and Allergic Diseases Center of the University of Virginia is primarily concerned with investigating the etiology of asthma focusing on the foreign proteins that can cause an immune response of the type characteristic of this disease, i.e. T cells that produce IL-4 and IL-5, IgE antibodies and eosinophils. The Center combines studies on the common indoor allergens, respiratory viruses, and allergens derived from comensal organisms, which are causally related to asthma in infants, school age children and adults. Studies proposed include four main areas: i) Site-directed mutagenesis will be used to create variants of recombinant allergens (e.g. the mite allergen Der p 2) that stimulate T cells but do not bind to IgE antibodies, and could be used for immunotherapy. In parallel, the tertiary structure of Der p 2 will be determined using Nuclear Magnetic Resonance (NMR) and X-ray crystallography. Together, these studies will provide a structural basis for dissecting the immune response to allergens. ii) Immunization with the G or F proteins of Respiratory Syncytial Virus (RSV) leads to different cytokine patterns when mice are infected with the virus. This model will be used to investigate the T cell responses that result in IL-5 production and the eosinophil infiltrate in the lungs. RSV in infancy is the most common cause of bronchiolitis. The G and F proteins will be used to investigate T cell responses in children who have been infected with RSV. iii) Population based and prospective studies on the role of allergen exposure in asthma will be used to investigate fact&s that can influence inflammation and symptoms of asthma in children. These studies will use PCR for rhinovirus and simple markers of inflammation (e.g. nasal ECP and exhaled NO) which are suitable for epidemiological studies or monitoring of acute asthma. iv) Patients with late onset or intrinsic asthma will be investigated to identify' those cases where a search for the causes of eosinophilia and/or sinusitis should be focused. A subgroup of these patients are colonized with Trichophyton, and have T cells that produce IL-5 in response to fungal proteins. Using cultures, skin tests and immunochemistry the studies will identify and characterize other potential allergens including the bacterial flora of sinuses. The D&E Project will investigate the role of cockroach and dust mite allergen control in the treatment of asthma among inner city children. All of the proposed studies are designed to identify aspects of the etiology of asthma that could lead directly to improved management.
Funding Period: 1993-09-01 - 2001-08-31
more information: NIH RePORT

Top Publications

  1. pmc Delayed anaphylaxis, angioedema, or urticaria after consumption of red meat in patients with IgE antibodies specific for galactose-alpha-1,3-galactose
    Scott P Commins
    Asthma and Allergic Diseases Center, University of Virginia Health System, Charlottesville, VA, USA
    J Allergy Clin Immunol 123:426-33. 2009
  2. pmc Major increase in allergic sensitization in schoolchildren from 1996 to 2006 in northern Sweden
    Eva Ronmark
    Obstructive Lung Disease in Northern Sweden Studies, Department of Medicine, Sunderby Central Hospital of Norrbotten, Lulea, Sweden
    J Allergy Clin Immunol 124:357-63, 63.e1-15. 2009
  3. ncbi The Obstructive Lung Disease in Northern Sweden (OLIN) longitudinal paediatric study I--the first 10 years
    E Ronmark
    The OLIN Studies, Department of Medicine, Sunderby Central Hospital of Norrbotten, Lulea, Sweden
    Clin Respir J 2:26-33. 2008
  4. ncbi SNOR and wheeze: the asthma enzyme?
    Edward M Henderson
    Pediatric Respiratory Medicine, University of Virginia Health System, Charlottesville, VA 22908, USA
    Trends Mol Med 11:481-4. 2005
  5. pmc Endogenous S-nitrosoglutathione modifies 5-lipoxygenase expression in airway epithelial cells
    Khalequz Zaman
    Department of Pediatrics, University of Virginia Health System, P O Box 800386, Charlottesville, VA 22908, USA
    Am J Respir Cell Mol Biol 34:387-93. 2006
  6. ncbi Tracheal aspirate pH is alkaline in pre-term human infants
    A O Paget-Brown
    University of Virginia Children s Hospital, Pediatric Respiratory Medicine, Charlottesville, VA 22908, USA
    Eur Respir J 30:840-2. 2007
  7. pmc Pulmonary eosinophilia is attenuated by early responding CD8(+) memory T cells in a murine model of RSV vaccine-enhanced disease
    Whitney W Stevens
    Beirne B Carter Center for Immunology Research, University of Virginia, Charlottesville, Virginia 22908, USA
    Viral Immunol 22:243-51. 2009
  8. pmc The relevance of tick bites to the production of IgE antibodies to the mammalian oligosaccharide galactose-α-1,3-galactose
    Scott P Commins
    Asthma and Allergic Diseases Center, University of Virginia Health System, Charlottesville, VA, USA
    J Allergy Clin Immunol 127:1286-93.e6. 2011

Detail Information

Publications8

  1. pmc Delayed anaphylaxis, angioedema, or urticaria after consumption of red meat in patients with IgE antibodies specific for galactose-alpha-1,3-galactose
    Scott P Commins
    Asthma and Allergic Diseases Center, University of Virginia Health System, Charlottesville, VA, USA
    J Allergy Clin Immunol 123:426-33. 2009
    ..Recent work, however, has shown that IgE antibodies to galactose-alpha-1,3-galactose (alpha-gal), a carbohydrate commonly expressed on nonprimate mammalian proteins, are capable of eliciting serious, even fatal, reactions...
  2. pmc Major increase in allergic sensitization in schoolchildren from 1996 to 2006 in northern Sweden
    Eva Ronmark
    Obstructive Lung Disease in Northern Sweden Studies, Department of Medicine, Sunderby Central Hospital of Norrbotten, Lulea, Sweden
    J Allergy Clin Immunol 124:357-63, 63.e1-15. 2009
    ..Time trends for allergic sensitization are poorly known...
  3. ncbi The Obstructive Lung Disease in Northern Sweden (OLIN) longitudinal paediatric study I--the first 10 years
    E Ronmark
    The OLIN Studies, Department of Medicine, Sunderby Central Hospital of Norrbotten, Lulea, Sweden
    Clin Respir J 2:26-33. 2008
    ..Prospective studies of asthma and allergic conditions based on the general population are scarce...
  4. ncbi SNOR and wheeze: the asthma enzyme?
    Edward M Henderson
    Pediatric Respiratory Medicine, University of Virginia Health System, Charlottesville, VA 22908, USA
    Trends Mol Med 11:481-4. 2005
    ....
  5. pmc Endogenous S-nitrosoglutathione modifies 5-lipoxygenase expression in airway epithelial cells
    Khalequz Zaman
    Department of Pediatrics, University of Virginia Health System, P O Box 800386, Charlottesville, VA 22908, USA
    Am J Respir Cell Mol Biol 34:387-93. 2006
    ..However, GSNO at concentrations>5microM suppresses 5-LO expression. These data suggest that GSNO might inhibit 5-LO expression in the clinical setting...
  6. ncbi Tracheal aspirate pH is alkaline in pre-term human infants
    A O Paget-Brown
    University of Virginia Children s Hospital, Pediatric Respiratory Medicine, Charlottesville, VA 22908, USA
    Eur Respir J 30:840-2. 2007
    ..The present data demonstrate for the first time that premature infants may have abnormal tracheal aspirate pH...
  7. pmc Pulmonary eosinophilia is attenuated by early responding CD8(+) memory T cells in a murine model of RSV vaccine-enhanced disease
    Whitney W Stevens
    Beirne B Carter Center for Immunology Research, University of Virginia, Charlottesville, Virginia 22908, USA
    Viral Immunol 22:243-51. 2009
    ..Rather, we demonstrate that IL-10 produced by early responding CD8(+) Tm cells may regulate the pulmonary eosinophilia development observed in RSV vaccine-enhanced disease...
  8. pmc The relevance of tick bites to the production of IgE antibodies to the mammalian oligosaccharide galactose-α-1,3-galactose
    Scott P Commins
    Asthma and Allergic Diseases Center, University of Virginia Health System, Charlottesville, VA, USA
    J Allergy Clin Immunol 127:1286-93.e6. 2011
    ..Most of these patients had tolerated meat for many years previously. The implication is that some exposure in adult life had stimulated the production of these IgE antibodies...