Changes in markers associated with dendritic cells driving the differentiation of either TH2 cells or regulatory T cells correlate with clinical benefit during allergen immunotherapy

Sialylated Fetuin-A as a candidate predictive biomarker for successful grass pollen allergen immunotherapy

“…15 A flow cytometric analysis confirmed an upregulation in such DCs of CD83 and CD86 costimulatory markers in the presence of FetA but not AsialoFetA (Fig 5, C). Similarly, DCs differentiated in the presence of FetA secreted significantly higher levels of IL-6, IL-8, IL-10, and TNF-a when compared with AsialoFetA-treated DCs (Fig 5, D).…”

“…It is noteworthy that the synergy observed between LPS and FetA in those assays was totally abrogated by adding the TLR4 antagonist LPS-RS (data not shown), 33 confirming that FetA and LPS act in combination to activate the TLR4 pathway. Furthermore, expression by DCs of a gene associated with DC2 polarization (ie, PADI2) 15 was upregulated in the presence of FetA but not AsialoFetA (Fig 5, E). In contrast, expression of genes associated with DCs driving the differentiation of T H 1 cells or DCReg differentiation, such as MX1 or C1QA, respectively, 14 was strongly downregulated when DCs were cultured in the presence of FetA but not AsialoFetA (Fig 5, E).…”

“…[11][12][13] Recently, we also reported that early onset of clinical efficacy is correlated with induction in peripheral blood of monocyte-derived regulatory dendritic cells, driving the differentiation of regulatory T cells (DCRegs) concomitantly with a decrease in proallergic type 2 dendritic cells (DCs; ie, dendritic cells driving the differentiation of T H 2 cells [DC2s]). 14,15 Although all those biological changes represent candidate follow-up markers reflecting efficacy after AIT has been initiated, patient selection would further benefit from identification of biomarkers predicting the likelihood of clinical responsiveness before starting treatment. 8 Patients' eligibility to immunotherapy is currently based on the determination of IgE reactivity to a specific allergen by means of skin prick or in vitro testing.…”

Allergen-Specific Immunotherapy Follow-Up by Measuring Allergen-Specific IgG as an Objective Parameter

“…Likewise, a report using transcriptomic and proteomic approaches demonstrated that PBMCs from allergic patients downregulate the expression of markers related with DC driving the differentiation of Th2 cells, whereas upregulate markers associated with DC driving differentiation of T regulatory cells, after only 4 months of SLIT. These results indicate that AIT has an early effect on antigen-presenting cells that trigger the Th2 downregulation [42]. Therefore, the changes evoked during AIT regimen on antigen-presenting cells, with a predominance of DC tolerogenic subsets inducing the development of T regulatory (Treg) cells, may be part of the mechanism behind of the therapeutic efficacy observed in AIT (Figure 2).…”

“…Some evidences reveal that AIT can affect directly the phenotype of the antigen-presenting cells correlating with clinical improvement in patients with allergic diseases [40][41][42]. A regulatory dendritic cell signature correlating with the clinical efficacy after allergen-specific sublingual immunotherapy (SLIT) has been observed in peripheral blood mononuclear cells (PBMCs) from clinical allergic responders in comparison with nonresponders or patients that received only placebo [40].…”