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August 3, 2017

Allergy Biomarkers Found in a Sub-Subgroup of T Helper Cells

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    Newly identified T helper cells dubbed TH2A cells are responsible for causing allergic symptoms. These pathogenic cells can be distinguished from their protective counterparts by specific markers. [Carla Schaffer/E. Wambre et al./AAAS]

     

  • The “bad” T helper cells that drive allergic reactions have been hiding among the “good” T helper cells, the ones that work as they should, protecting us from pathogens. But the bad T helper cells have been found out. Now that their unique features have been identified, these pathogenic cells may become helpful in fact and not just in name. They may be tracked and made to serve as allergy biomarkers. These cells may help us improve our evaluations of allergy treatments.

    Researchers based at Virginia Mason Medical Institute in Seattle, WA, have identified a distinctive signature of six surface markers that sets pathogenic type 2 helper T cells (TH2) cells apart from nonpathogenic TH2 cells. The allergy-inducing cells, dubbed TH2A cells, were present in 80 individuals allergic to a variety of substances, including tree pollen, mold, house dust mites, and peanuts, but not in 34 people without allergies.

    Additional details appeared August 2 in the journal Science Translational Medicine, in an article entitled “A Phenotypically and Functionally Distinct Human TH2 Cell Subpopulation Is Associated with Allergic Disorders.” This article explains how the Virginia Mason team identified T helper cells with a stable allergic disease–related phenotype.

    “[The pathogenic] cells are terminally differentiated CD4+ T cells (CD27 and CD45RB) characterized by coexpression of CRTH2, CD49d, and CD161 and exhibit numerous functional attributes distinct from conventional TH2 cells,” wrote the article’s authors. “Transcriptome analysis further revealed a distinct pathway in the initiation of pathogenic responses to allergen, and elimination of these cells is indicative of clinical responses induced by immunotherapy.”

    Allergic reactions arise from an inappropriate immune response to otherwise innocuous substances such as pollen, mold, or peanuts, initiated by a group of immune cells known as the TH2 subset. Until now, scientists have been unable to distinguish allergy-causing TH2 cells from the genuinely helpful cells that play vital roles in defending the body against pathogens.

    TH2A cells produced multiple inflammatory signaling molecules, and the researchers further observed unique gene expression patterns in TH2A cells involving pathways that drive allergic responses. In a clinical trial evaluating the efficacy of an experimental peanut allergy treatment, the Virginia Mason scientists, led by Erik Wambre, Ph.D., noted a direct correlation between desensitization to nuts and decreased frequency of TH2A cells. According to the authors of the current study, the cells could be used as much-needed clinical biomarkers to evaluate the effectiveness of allergy treatments.

    Besides identifying new biomarkers, the current study may lead to new therapeutic targets, potentially benefiting many who suffer from allergies. Almost 50 million Americans suffer from nasal allergies, and life-threatening food allergies can cause as many as 200 deaths per year in the United States. 

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