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.
BACKGROUND
Japanese cedar (Cryptomeria japonica) pollinosis is one of the most prevalent allergies in Japan. Recently, two reports described the positive effects of sublingual immunotherapy (SLIT) against Japanese cedar pollinosis. However, the therapeutic biomarkers for SLIT are still unclear. We performed this unblinded, nonrandomized, open-label study to identify therapeutic biomarkers for SLIT against Japanese cedar pollinosis.


METHODS
We performed an open-label study during one pollinosis season in 2007, enrolling 19 patients from in-house volunteers suffering from Japanese cedar pollinosis. Peripheral blood was obtained from all participants before SLIT treatment as well as before and after the pollen season. The plasma levels of an immunoglobulin specific to a major allergen (Cry j 1) were determined. We analyzed the induction of regulatory T cells (iTregs), namely IL-10(+)Foxp3(+) cells in CD25(+)CD4(+) leukocytes, by flow cytometry. The Th2-type responses were analyzed by cytokine production from peripheral blood mononuclear cells after stimulation with Cry j 1. Clinical symptoms were estimated using a quality of life questionnaire in the middle of the pollen season.


RESULTS
The difference in numbers of iTregs between the medium-only control cell culture and cells stimulat- ed with Cry j 1 was significantly decreased in the non-SLIT group but was unchanged in the SLIT group after the pollen season. The subgroup of the SLIT group with increased iTregs showed more attenuated Th2-type cytokine profiles, and symptom scores in the subgroup with increased iTregs were significantly lower than those in the subgroup with decreased iTregs.


CONCLUSIONS
The antigen-specific iTreg level is a potential therapeutic biomarker that correlates with clinical pollinosis symptoms and may be involved in the therapeutic mechanisms of SLIT.
Fujimura
Takashi
T
Department of Otolaryngology, Head and Neck Surgery, Graduate School of Medicine, Chiba University, Chuo-ku, Chiba, Japan.
Yonekura
Syuji
S
Taniguchi
Yuriko
Y
Horiguchi
Shigetoshi
S
Saito
Akemi
A
Yasueda
Hiroshi
H
Nakayama
Toshinori
T
Takemori
Toshitada
T
Taniguchi
Masaru
M
Sakaguchi
Masahiro
M
Okamoto
Yoshitaka
Y
D000286:Administration, Sublingual; D000328:Adult; D052179:Antigens, Plant / Q000276:immunology; D054316:Biomarkers, Pharmacological / Q000378:metabolism; D015704:CD4 Antigens / Q000096:biosynthesis; D002452:Cell Count; D002478:Cells, Cultured; D032485:Cryptomeria; D003888:Desensitization, Immunologic; D018450:Disease Progression; D005260:Female; D051858:Forkhead Transcription Factors / Q000096:biosynthesis*; D006801:Humans; D007073:Immunoglobulin E / Q000097:blood; D016753:Interleukin-10 / Q000096:biosynthesis; D053645:Interleukin-2 Receptor alpha Subunit / Q000096:biosynthesis; D008297:Male; D008875:Middle Aged; D010940:Plant Proteins / Q000276:immunology; D006255:Rhinitis, Allergic, Seasonal / Q000175:diagnosis* / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology / Q000503:physiopathology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000378:metabolism* / Q000473:pathology
D052179:Antigens, Plant; D054316:Biomarkers, Pharmacological; D015704:CD4 Antigens; C065290:Cry j I protein, Cryptomeria japonica; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D053645:Interleukin-2 Receptor alpha Subunit; D010940:Plant Proteins; D016753:Interleukin-10; D007073:Immunoglobulin E