Exploring novel systemic biomarker approaches in grass‐pollen sublingual immunotherapy using omics

Abstract

Background Sublingual allergen‐specific immunotherapy (SLIT) intervention improves the control of grass pollen allergy by maintaining allergen tolerance after cessation. Despite its widespread use, little is known about systemic effects and kinetics associated to SLIT, as well as the influence of the patient sensitization phenotype (Mono‐ or Poly‐sensitized). In this quest, omics sciences could help to gain new insights to understand SLIT effects. Methods 47 grass‐pollen‐allergic patients were enrolled in a double‐blind, placebo‐controlled, multicenter trial using GRAZAX® during 2 years. Immunological assays (sIgE, sIgG4, and ISAC) were carried out to 31 patients who finished the trial. Additionally, serum and PBMCs samples were analyzed by metabolomics and transcriptomics, respectively. Based on their sensitization level, 22 patients were allocated in Mono‐ or Poly‐sensitized groups, excluding patients allergic to epithelia. Individuals were compared based on their treatment (Active/Placebo) and sensitization level (Mono/Poly). Results Kinetics of serological changes agreed with those previously described. At two years of SLIT, there are scarce systemic changes that could be associated to improvement in systemic inflammation. Poly‐sensitized patients presented a higher inflammation at inclusion, while Mono‐sensitized patients presented a reduced activity of mast cells and phagocytes as an effect of the treatment. Conclusions The most relevant systemic change detected after two years of SLIT was the desensitization of effector cells, which was only detected in Mono‐sensitized patients. This change may be related to the clinical improvement, as previously reported, and, together with the other results, may explain why clinical effect is lost if SLIT is discontinued at this point.

Biomarkers in Hereditary Angioedema

“…Moreover, this keyword generates over 40,000 results in the PubMed search (filters applied: clinical trial, humans) [2]. In the field of allergy and clinical immunology, biomarkers have been recently studied in numerous diseases, such as atopic dermatitis [3], allergic rhinitis [4], bronchial asthma [5,6], food allergy [7], and severe drug hypersensitivity reactions [8]. Most commonly, investigators have searched for new biomarkers that would predict disease severity [3,5], determine the risk of severe reactions [7,8], or discriminate between disease endotypes [6].…”

Molecular allergology and its impact in specific allergy diagnosis and therapy

“…Main AIT mechanisms involve early effector cells de-sensitization and progressive onset of tolerance through a regulatory response that needs at least three years to be consolidated 5,13 . Dose-finding studies are usually performed during relatively short times, and thus effective dose is adjusted to target desensitization mechanism and to major allergen doses…”

“…The need to advance on personalized medicine approaches to predict intervention outcome and safety -and to monitor AIT effect -is imperative 131 . System biology approaches are being explored to understand AIT response 5 . These new approaches help to understand biological effect kinetics and provide new tools to evaluate new AIT product approaches.…”

“…Single or multiplexed, allergenic molecules are routinely used and have changed the way we diagnose 4 . Lastly, but not least, some sensitization profiles are linked to different clinical phenotypes, and can be used to stratify allergic patients, to predict intervention outcomes, and to perform system biology studies that open new avenues for allergy disease management [5][6][7][8][9][10][11] .…”

“…Based on these studies, a better understanding of AIT mechanisms is now possible. From allergen-specific effector cell desensitization 5,[12][13][14] to a progressive onset of T and B cell-mediated regulatory mechanisms [15][16][17][18][19] responsible for the disease-modifying effect, their temporal alignment is critical to establish best AIT practices. In this context, the quality of the extract used -and its standardization -, the knowledge of patient's sensitization profiles, and the link to the AIT product used are pivotal to maximize the odds of AIT success.…”