A new study published in the Journal of Investigative Dermatology suggests that people with systemic mastocytosis (SM) may struggle to develop the long-lasting immune memory needed to maintain protection after venom immunotherapy (VIT).
Researchers compared immune responses in patients with and without clonal mast cell diseaseMast cell disease A group of conditions in which mast cells behave abnormally by building up in excess, releasing chemicals too easily or both. Includes mastocytosis, mast cell activation syndrome and hereditary alpha-tryptasemia. who had experienced Hymenoptera venom–induced anaphylaxisAnaphylaxis A severe allergic reaction that can turn fatal without treatment. Patients with SM are at a higher risk of developing anaphylaxis.. Participants were assessed before treatment and then again after more than three years of VIT.
As expected, those with clonal mast cell disease had significantly higher levels of tryptaseTryptase A protein enzyme that is primarily produced by mast cells and stored in small pockets within the cells, known as granules. High levels of tryptase are a key indicator of SM., a marker linked to mast cellMast cell A type of white blood cell produced in the bone marrow. They help defend against infections and play a key role in allergic reactions. In SM, mast cells become overactive and build up throughout the body. burden. Wasp venom–specific immunoglobulin E (IgE) antibodies were higher in patients without clonal mast cell disease than in those with it, and IgE levels tended to fall during immunotherapy only in the non-clonal group. Both groups showed increases in venom-specific IgG4 antibodies during treatment, a recognized sign that desensitization is working.
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Immune changes indicating successful allergy immunotherapy, including shifts in CD4 T-cells, follicular helper T cells and follicular regulatory T cells, occurred in both groups.
However, key differences appeared in CD8 memory T cells. After long-term immunotherapy, individuals without clonal mast cell disease had increased levels of CD8 central memory T cells, which are associated with long-lasting immune tolerance. In contrast, patients with clonal mast cell disease developed higher levels of CD8 effector memory T cells, which are linked to faster inflammatory responses.
In a laboratory setting, when researchers exposed immune cells to wasp venom, cells from people with clonal mast cell disease produced less IL-6, a signaling molecule that helps build long-term immune memory.
The researchers said these results suggest that reduced IL-6 responses and a failure to build CD8 central memory T cells may help explain why long-term tolerance is harder to maintain after venom immunotherapy in SM.
“Together, these findings make IL-6 and CD8 TCMs interesting targets for inducing long-term tolerance in the future, as specifically activating CD8 TCMs might enhance the efficacy and efficiency of VIT,” they concluded.
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