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Therapeutic effects and biomarkers in sublingual immunotherapy: a review.

Fujimura T, Okamoto Y, Taniguchi M - J Allergy (Cairo) (2012)

Bottom Line: However, the mechanism of SLIT and associated biomarkers are not fully understood.In this review, we focus on the safety, therapeutic effects, including prolonged effects after treatment, and new methods of SLIT.Finally, we discuss immunological mechanisms of SLIT with a focus on oral dendritic cells and facilitated antigen presentation.

View Article: PubMed Central - PubMed

Affiliation: Research Center for Allergy and Immunology, Yokohama Institute, RIKEN, 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama, Kanagawa 230-0045, Japan.

ABSTRACT
Immunotherapy is considered to be the only curative treatment for allergic diseases such as pollinosis, perennial rhinitis, asthma, and food allergy. The sublingual route is widely applied for immunotherapy for allergy, instead of the conventional administration by subcutaneous route. A recent meta-analysis of sublingual immunotherapy (SLIT) has shown that this approach is safe, has positive clinical effects, and provides prolonged therapeutic effects after discontinuation of treatment. However, the mechanism of SLIT and associated biomarkers are not fully understood. Biomarkers that change after or during SLIT have been reported and may be useful for response monitoring or as prognostic indicators for SLIT. In this review, we focus on the safety, therapeutic effects, including prolonged effects after treatment, and new methods of SLIT. We also discuss response monitoring and prognostic biomarkers for SLIT. Finally, we discuss immunological mechanisms of SLIT with a focus on oral dendritic cells and facilitated antigen presentation.

No MeSH data available.


Related in: MedlinePlus

Response-monitoring and prognostic biomarkers for SLIT [36]. (a) Total scores from a QOL questionnaire are plotted for the SLIT group (All), a subgroup with increased antigen-specific Treg in the SLIT group (Inc), a subgroup with decreased antigen-specific Treg in the SLIT group (Dec), and the placebo (Plc) group after 2 years of treatment. **P < 0.01 (Mann-Whitney U-test). (b) SMSs in the peak pollen season for patients with low and high sIgE/tIgE ratios in the SLIT group (Act.). *P < 0.05. (c) Correlation between SMSs after 2 years of SLIT treatment and sIgE/tIgE ratios before treatment in the SLIT (Act, closed diamonds) and placebo (Plc, open diamonds) groups. Statistical data were obtained with Spearman correlation analysis. N.S.: not significant.
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fig2: Response-monitoring and prognostic biomarkers for SLIT [36]. (a) Total scores from a QOL questionnaire are plotted for the SLIT group (All), a subgroup with increased antigen-specific Treg in the SLIT group (Inc), a subgroup with decreased antigen-specific Treg in the SLIT group (Dec), and the placebo (Plc) group after 2 years of treatment. **P < 0.01 (Mann-Whitney U-test). (b) SMSs in the peak pollen season for patients with low and high sIgE/tIgE ratios in the SLIT group (Act.). *P < 0.05. (c) Correlation between SMSs after 2 years of SLIT treatment and sIgE/tIgE ratios before treatment in the SLIT (Act, closed diamonds) and placebo (Plc, open diamonds) groups. Statistical data were obtained with Spearman correlation analysis. N.S.: not significant.

Mentions: Candidate biomarkers for response-monitoring or prognosis have been proposed and evaluated in many studies [4, 57, 58]. IL10 and Treg cells appear to be involved in the therapeutic mechanism of SLIT [59–61]. We reported upregulation of antigen-specific Treg cells (IL10+Foxp3+ cells) in CD25+CD4+ leukocytes from pre- to postpollen season as a response-monitoring biomarker for SLIT [36, 62]. Among patients treated with SLIT, total QOL and QOL-symptom scores after 2 years of treatment significantly improved in a subgroup with increased Treg cells compared with the placebo group, whereas the scores in a subgroup with decreased Treg cells were similar to those in the placebo group (Figure 2(a)). We also proposed that the ratio of antigen-specific IgE to total IgE (sIgE/tIgE) was a candidate as a prognostic biomarker for SLIT in a DBPC trial [36]. SMS in the SLIT group was correlated with the sIgE/tIgE ratio before treatment and was significantly improved in patients with a low sIgE/tIgE ratio compared to that in patients with a high sIgE/tIgE ratio (Figures 2(b) and 2(c)) [36]. The sIgE/tIgE ratio has been found to be significantly higher in responders than in nonresponders following 4-year immunotherapy [63]. In this study, responders to the immunotherapy (42 patients for SCIT and 103 patients for SLIT) showed higher grass- or mite-specific IgE/tIgE ratio than nonresponders (34 patients for SCIT and 100 patients for SLIT) evaluated with VAS score. In our trial, this ratio did not differ significantly between responders and nonresponders [36]. Further validation studies with a large sample size are needed before these biomarkers can be applied in the clinical management of SLIT.


Therapeutic effects and biomarkers in sublingual immunotherapy: a review.

Fujimura T, Okamoto Y, Taniguchi M - J Allergy (Cairo) (2012)

Response-monitoring and prognostic biomarkers for SLIT [36]. (a) Total scores from a QOL questionnaire are plotted for the SLIT group (All), a subgroup with increased antigen-specific Treg in the SLIT group (Inc), a subgroup with decreased antigen-specific Treg in the SLIT group (Dec), and the placebo (Plc) group after 2 years of treatment. **P < 0.01 (Mann-Whitney U-test). (b) SMSs in the peak pollen season for patients with low and high sIgE/tIgE ratios in the SLIT group (Act.). *P < 0.05. (c) Correlation between SMSs after 2 years of SLIT treatment and sIgE/tIgE ratios before treatment in the SLIT (Act, closed diamonds) and placebo (Plc, open diamonds) groups. Statistical data were obtained with Spearman correlation analysis. N.S.: not significant.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3303629&req=5

fig2: Response-monitoring and prognostic biomarkers for SLIT [36]. (a) Total scores from a QOL questionnaire are plotted for the SLIT group (All), a subgroup with increased antigen-specific Treg in the SLIT group (Inc), a subgroup with decreased antigen-specific Treg in the SLIT group (Dec), and the placebo (Plc) group after 2 years of treatment. **P < 0.01 (Mann-Whitney U-test). (b) SMSs in the peak pollen season for patients with low and high sIgE/tIgE ratios in the SLIT group (Act.). *P < 0.05. (c) Correlation between SMSs after 2 years of SLIT treatment and sIgE/tIgE ratios before treatment in the SLIT (Act, closed diamonds) and placebo (Plc, open diamonds) groups. Statistical data were obtained with Spearman correlation analysis. N.S.: not significant.
Mentions: Candidate biomarkers for response-monitoring or prognosis have been proposed and evaluated in many studies [4, 57, 58]. IL10 and Treg cells appear to be involved in the therapeutic mechanism of SLIT [59–61]. We reported upregulation of antigen-specific Treg cells (IL10+Foxp3+ cells) in CD25+CD4+ leukocytes from pre- to postpollen season as a response-monitoring biomarker for SLIT [36, 62]. Among patients treated with SLIT, total QOL and QOL-symptom scores after 2 years of treatment significantly improved in a subgroup with increased Treg cells compared with the placebo group, whereas the scores in a subgroup with decreased Treg cells were similar to those in the placebo group (Figure 2(a)). We also proposed that the ratio of antigen-specific IgE to total IgE (sIgE/tIgE) was a candidate as a prognostic biomarker for SLIT in a DBPC trial [36]. SMS in the SLIT group was correlated with the sIgE/tIgE ratio before treatment and was significantly improved in patients with a low sIgE/tIgE ratio compared to that in patients with a high sIgE/tIgE ratio (Figures 2(b) and 2(c)) [36]. The sIgE/tIgE ratio has been found to be significantly higher in responders than in nonresponders following 4-year immunotherapy [63]. In this study, responders to the immunotherapy (42 patients for SCIT and 103 patients for SLIT) showed higher grass- or mite-specific IgE/tIgE ratio than nonresponders (34 patients for SCIT and 100 patients for SLIT) evaluated with VAS score. In our trial, this ratio did not differ significantly between responders and nonresponders [36]. Further validation studies with a large sample size are needed before these biomarkers can be applied in the clinical management of SLIT.

Bottom Line: However, the mechanism of SLIT and associated biomarkers are not fully understood.In this review, we focus on the safety, therapeutic effects, including prolonged effects after treatment, and new methods of SLIT.Finally, we discuss immunological mechanisms of SLIT with a focus on oral dendritic cells and facilitated antigen presentation.

View Article: PubMed Central - PubMed

Affiliation: Research Center for Allergy and Immunology, Yokohama Institute, RIKEN, 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama, Kanagawa 230-0045, Japan.

ABSTRACT
Immunotherapy is considered to be the only curative treatment for allergic diseases such as pollinosis, perennial rhinitis, asthma, and food allergy. The sublingual route is widely applied for immunotherapy for allergy, instead of the conventional administration by subcutaneous route. A recent meta-analysis of sublingual immunotherapy (SLIT) has shown that this approach is safe, has positive clinical effects, and provides prolonged therapeutic effects after discontinuation of treatment. However, the mechanism of SLIT and associated biomarkers are not fully understood. Biomarkers that change after or during SLIT have been reported and may be useful for response monitoring or as prognostic indicators for SLIT. In this review, we focus on the safety, therapeutic effects, including prolonged effects after treatment, and new methods of SLIT. We also discuss response monitoring and prognostic biomarkers for SLIT. Finally, we discuss immunological mechanisms of SLIT with a focus on oral dendritic cells and facilitated antigen presentation.

No MeSH data available.


Related in: MedlinePlus