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Persistent regulatory T‐cell response 2 years after 3 years of grass tablet SLIT : Links to reduced eosinophil counts, sIgE levels, and clinical benefit
Author(s) -
Varona Rosa,
Ramos Tania,
Escribese Maria Marta,
Jimeno Lucia,
Galán Agustin,
Würtzen Peter A.,
Vega Francisco,
Marín Alicia,
Martín Santiago,
Carrera Ana C.,
Blanco Carlos,
Barber Domingo
Publication year - 2019
Publication title -
allergy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.363
H-Index - 173
eISSN - 1398-9995
pISSN - 0105-4538
DOI - 10.1111/all.13553
Subject(s) - medicine , discontinuation , immunotherapy , sublingual immunotherapy , immunology , clinical trial , eosinophil , immune system , asthma
Background In the first 2 years of grass tablet sublingual immunotherapy treatment, we have previously demonstrated a progressive development of a regulatory T‐cell response, which was preceded by an early decrease in the frequency of both IL ‐4+ cells and sIgE levels. A progressive increase in sIgG 4 levels and FAB blockage were also found. Methods By monitoring immunological kinetics during 3 years of active treatment + 2 years of follow‐up, we aimed to identify key immunological parameters that could explain sustained clinical benefit of grass tablet sublingual immunotherapy. Results Thirty patients completed the 5‐year clinical trial protocol. Although individual responses were heterogeneous, reduction in both sIgE and circulating IL ‐4+ cells compared to the initial 1‐ to 4‐month peak was maintained throughout the 3‐year treatment period and for 2 years after discontinuation. Meanwhile, after a 2‐year increase in sIgG 4, the levels were stabilized during the third year and decreased post‐therapy. FAB inhibition remained significantly inhibited throughout the study compared to preimmunotherapy in 83% of patients. A sustained regulatory T‐cell response, after IT cessation, occurs in two‐thirds of the patients. There was a statistical association between this regulatory response, the maintenance of lower eosinophil counts during grass pollen seasons, and sIgE titers lower than before immunotherapy treatment, and the latter were significantly associated with clinical response. Conclusion Our results suggest that the immunological mechanisms underlying the sustained response after 2 years of cessation of immunotherapy (3‐year treatment period) are linked to the acquisition and maintenance of a regulatory T‐cell response.