VI. Cytokines and Chemokines The mechanism by which AIT exerts its immunomodulatory effects has not been conclusively established. As allergic disorders are known to be characterized by a Th2 biased response, the pivotal role of AIT is believed to be inducing a shift in favor of a Th1 response. Being involved in nearly every step of immune response, the role of cytokines and chemokines in this T helper deviation should not be undertaken lightly.
In respect to this theory an up-regulation in Th1 related cytokines (IFN-?, IL-12) and T regulatory response related cytokines (IL-10, TGF-? and) is expected while, Th2 response related cytokines (IL-4, IL-13, IL-9, IL-17, TNF-?) decrease. However, the expected switch in cytokine profile has not been demonstrated by all studies. Several local nasal potential biomarkers have been shown to be modulated in response to AIT.1Chemokines are a group of small cytokines which have chemo-attractive functions playing an important role in the pathophysiology of allergic disorders. Although some studies report changes in the levels of serum chemokines associated with AIT, none of these were directly correlated with the clinical outcome. Some chemokines that have been investigated as potential biomarkers are listed below:- Increased following AIT: CCR42, Eotaxin2, Complement C4a3, Leptin4, Apolipoprotein3, Thymus and activation regulated protein (TARC)2, Transthyretin3, Signaling lymphocytic activation molecule2, Resistin 4- Decreased: Complement C3a, C5a5, Eotaxin1, TRAIL6- Unchanged: CCR32, Adiponectin7, Tryptase1, Leptin7, ECP1, Soluble HLA molecules8Currently, there is no validated consensus on potential cytokine or chemokine biomarkers that have a prognostic or predictive value in clinical response to AIT.
VIII. Cellular BiomarkersPotential cellular biomarkers associated with allergen immunotherapy response include regulatory T cells (Tregs), T helper cells (Th1, Th2), T follicular helper (Tfh) and T follicular regulatory (Tfr) cells, regulatory B cells (Bregs) and dendritic cells (DCs).9,10 The key cells involved in reversing the inflammatory process are the natural regulatory T cells (nTreg) that express the transcription factor forkhead box P3 (FOXP3), and inducible regulatory T (iTreg) cells, that secrete regulatory cytokines, such as IL-10, IL-35, and TGF-?.10 skewing the Th2 to Th1 immuneresponse.
