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Mast Cell Activation Profile and TFH13 Detection Discriminate Food Anaphylaxis Versus Sensitization

Ollé L1,2, García-García L2, Ruano M2,3,4, Bartra J2,3,4,5, González-Navarro EA6, Pérez M2, Roca-Ferrer J2, Pasca Ml*2,4,5,6, Martín M*1,2,4, Muñoz-Cano R*2,3,4,5

1Biochemistry and Molecular Biology Unit, Biomedicine Department, Faculty of  Medicine, University of Barcelona, Barcelona, Spain
2Clinical and Experimental Respiratory Immunoallergy (IRCE), Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain
3Allergy Department, Hospital Clinic, University of Barcelona, Barcelona, Spain
4ARADyAL, REI - RICOR, Instituto de Salud Carlos III, Madrid, Spain
5Medicine Department, Faculty of Medicine, University of Barcelona, Barcelona, Spain
6Immunology Department, Centre de Diagnòstic Biomèdic (CDB), Hospital Clínic, Barcelona, Spain

*Contributed equally to the work

J Investig Allergol Clin Immunol 2025; Vol. 35(3)
doi: 10.18176/jiaci.0995

BACKGROUND
The prevalence of food allergy (FA) has increased significantly, and the risk of developing anaphylaxis is unpredictable. Thus, discriminating between sensitized patients and those at risk of having a severe reaction is of utmost interest.
OBJECTIVE
To explore mast cell activation pattern and T follicular helper (TFH) 13 presence in sensitized and food anaphylaxis patients.
METHODS
Patients sensitized to Lipid transfer protein (LTP) were classified as anaphylaxis or sensitized depending on the symptoms elicited by LTP-containing food. CD34+-derived MCs from patients and controls were obtained, sensitized with pooled sera, and challenged with Pru p 3 (peach LTP). Degranulation, PGD2, and cytokine/chemokine release were measured. The TFH13 population was examined by flow cytometry in the peripheral blood of all groups. In parallel, LAD2 cells were activated similarly to patients’ MCs.
RESULTS
A distinguishable pattern of mast cell activation was found in anaphylaxis compared to sensitized patients. Robust degranulation, PGD2, and IL-8 and GM-CSF secretion were higher in anaphylaxis, whereas TFG- and CCL2 secretion increased in sensitized patients. Concomitantly, anaphylaxis patients had a larger TFH13 population. MC activation profile was dependent on the sera rather than the MC source. In agreement with that, LAD2 cells reproduce the same pattern as MCs from anaphylactic and sensitized patients.
CONCLUSION
The distinct profile of mast cell activation allows to discriminate between anaphylaxis and sensitized patients. Pooled sera may determine mast cell activation independently of mast cell origin. Besides, the presence of TFH13 cells in anaphylaxis patients points to an essential role of IgE affinity.

Key words: Anaphylaxis, Food allergy, IgE, Inflammation, Mast cells, TFH13