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 disease who had experienced Hymenoptera venom–induced 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 tryptase, a marker linked to mast cell 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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