Immunologic Effects of Sublingual Immunotherapy: Clinical Efficacy Is Associated With Modulation of Programmed Cell Death Ligand 1, IL-10, and IgG4
PURPOSE OF THE STUDY.
To evaluate an optimal treatment regimen for sublingual immunotherapy (SLIT) and investigate the underlying mechanism.
There were 62 Italian patients aged 19 to 60 years enrolled from a clinic in Milano, Italy, between February and September 2009. Inclusion criteria were a clinical history that suggested ragweed sensitization, a positive skin-prick-test result to ragweed pollen, and a clinical report of asthma and/or rhinoconjunctivitis.
The patients were randomly assigned to 1 of 4 treatment arms: preseasonal SLIT (5 months); seasonal SLIT (3 months); prolonged SLIT (5 months × 3 years); or no SLIT. Subjects on SLIT were treated with a median Amba1 (major ragweed allergen) dose of 120 mg/day. Clinical outcomes were recorded in daily diaries by the subjects during pollen season. Immunologic outcomes were assessed just before the initiation and completion of the SLIT regimen in the treatment groups and at the beginning and end of the study in the control groups. Clinical efficacy was evaluated with a visual analog scale. Lymphocyte subsets were evaluated by flow cytometry. Peripheral blood mononuclear cells were isolated and incubated with and without Amba1, and their cytokine profiles were analyzed by flow cytometry. Amba1-specific immunoglobulin G4 (IgG4) was measured by an enzyme-linked immunosorbent assay.
Clinical outcomes improved in all SLIT regimens compared with controls. This improvement was significantly better in the prolonged-SLIT (5 months × 3 years) compared to the other SLIT regimens. Cytokine analysis of CD4+ T lymphocytes, CD19+ B lymphocytes, and CD14+ monocytes revealed the following: interleukin 4 (IL-4)–producing cells were reduced in all SLIT regimens compared with controls, and IL-10–producing cells were increased in all SLIT regimens compared with controls. These results were statistically significant compared with controls in all but CD4+ IL-4–producing cells, and the results were similar across all treatment arms. All SLIT regimens resulted in an increase in Amba1-specific IgG4, and this increase was most impressive in the prolonged-SLIT treatment arm.
Although all SLIT regimens resulted in an improvement in clinical efficacy, prolonged SLIT was the most effective. The reduction in IL-4 and increase in IL-10 production is consistent with observations from subcutaneous immunotherapy studies and provides insight into the mechanism of SLIT. These cytokine changes might serve as an objective marker of efficacy of SLIT for patients on treatment.
Further evaluation of SLIT is of particular importance in the pediatric population because of its less invasive method of administration compared with injection immunotherapy and its improved safety profile. However, more studies are needed before the therapy makes it to US practice.
- Copyright © 2011 by the American Academy of Pediatrics