A Randomized Controlled Trial of Sublingual Immunotherapy for Japanese Cedar Pollinosis

Abstract

Background: Japanese cedar pollen represents an important and unique allergen. Sublingual immunotherapy (SLIT) has been suggested to be a highly effective route of desensitization against a variety of allergens. However, little information is available about its use in cedar pollen allergy. Methods: A blinded randomized, placebo-controlled trial employing SLIT for cedar pollinosis was conducted over a period of 6 months. Sixty-seven subjects were enrolled and the symptom scores during the pollen season were evaluated by a symptom diary, measurement of cedar-specific IgE and IgG4, and determination of Cry j-specific Th2 clones before SLIT and before and after the pollen season. Results: No major adverse effects were observed in either group. The serum-specific IgG4 activity increased significantly after SLIT in the active group. The active group also exhibited significantly lower symptom scores compared to the placebo. The specific Th2 clone sizes were not significantly different between the groups before the pollen season. However, an increase in the clone size was observed after the pollen season in the placebo group, but not in the active group. Conclusion: Use of SLIT for Japanese cedar pollinosis was found to be safe and associated with an increase in cedar-specific IgG4 levels. Such therapy inhibited the increase in Cry j-specific Th2 clone size induced by pollen exposure. Finally, use of SLIT resulted in significant improvement of the clinical symptoms of cedar pollinosis in this patient population. These observations suggest that SLIT may offer another safe approach to the management of cedar pollinosis.

The Induced Regulatory T Cell Level, Defined as the Proportion of IL-10⁺Foxp3⁺ Cells among CD25⁺CD4⁺ Leukocytes, Is a Potential Therapeutic Biomarker for Sublingual Immunotherapy: A Preliminary Report

“…The trial was performed from October 2006 to June 2007. The treatment protocol consisted of graded courses of the extract in 50% glycerol, followed by maintenance therapy [4]. The extract was graded in 3 strengths: 20, 200 and 2,000 Japanese Allergy Units (JAU)/ml.…”

“…The concentration of purified Cry j 1 was determined by the Lowry method using a detergent-compatible protein assay reagent (BioRad Laboratories Inc., Hercules, Calif., USA). CS712, which is a recombinant protein with 7 conjugated regions of T cell epitopes from Cry j 1 and Cry j 2 [4,5], was kindly provided by Daiichi Sankyo Co. Ltd. (Tokyo, Japan).…”

“…Recently, two reports have described the positive clinical effects of sublingual immunotherapy (SLIT) against Japanese cedar pollinosis [3,4]. A randomized double-blind study reported that efficacy variable scores in an active treatment group were significantly lower than those in a placebo group, and the quality of life (QOL) symptom score of the active group was almost half that of the placebo group [3].…”

“…We also previously reported that active treatment significantly ameliorated symptom scores and symptom-medication scores compared with placebo in a randomized controlled trial. Furthermore, we reported that SLIT decreased the number of Th2 clones specific to CS712, namely recombinant protein-conjugated T cell epitopes from Cry j 1 and Cry j 2 [4,5]. …”

Sublingual immunotherapy for Japanese cedar pollinosis: potential biomarkers predicting therapeutic responses

“…SLIT increases serum levels of antigen-specific IgG4 and also increases the antigen-specific IgG4/IgE ratio [19,20], and it has been suggested that serum IgG acts as blocking antibody and is associated with symptomatic improvement [21]. In Japan, it was reported that allergen-specific SLIT increases serum Cry j 1-specific IgG4 antibody in patients with JC pollinosis [22].…”