Antigen-Specific TH Cell Monitoring by CD154 Expression in Japanese Cedar-Specific SCIT

Abstract

M O N D A Y 721 Local Nasal 'Protective' Immunoglobulin G4 (IgG4) Responses in Nasal Fluid Following Grass Pollen Sublingual Immunotherapy Nausheen Saleem, BSc(Hons), Adam Chaker, MD, Ulrich Zissler, Carsten B. Schmidt-Weber, PhD, Stephen R. Durham, MA, MD, FRCP, Mohamed H. Shamji, BSc, MSc, PhD; Imperial College London, Universitatsklinkum Dusseldorf, Dusseldorf, Germany, ENT department, TU Munich, M€unchen, Germany, ENT department, TU Munich, Imperial College, London, United Kingdom, Medical Research Council and Asthma UK Centre for Allergic Mechanisms of Asthma, UK, MRC & Asthma UK Centre in Allergic Mechanisms of Asthma, Imperial College London, United Kingdom. RATIONALE: Grass pollen sublingual immunotherapy (SLIT) is associated with induction of serum IgG4-associated blocking antibodies that prevent IgE-facilitated allergen binding to B cells (IgE-FAB). We hypothesised that local nasal inhibitory IgG4 antibodies are also induced following SLIT. METHODS: Nasal fluids were obtained from SLIT-treated patients (n57), untreated allergics (n57) and non-atopic controls (n58). Specific IgE and IgG4 to Phleum pratense (Phl p) components were measured by ISAC microarray technology. Inhibitory activity of nasal fluid and serum was measured using the IgE-FAB assay. RESULTS: Untreated allergics had elevated levels of rPhl p 1 (p50.01) and rPhl p 5-specific IgE in nasal fluid compared to non-atopic controls. SLIT-treated patients showed a trend for an increase in rPhl p 1 (mean+/SE, 6.062.7 ISU) and rPhl p 5-specific IgE (2.162.6 ISU) compared to untreated allergics (p50.12). Recombinant Phl p 5-specific IgG4 levels were increased in SLIT-treated patients compared to untreated allergics (p50.02) and non-atopic controls (p50.003). Inhibitory activity in nasal fluid for co-operative binding of allergen-IgE complexes to B cells in SLITtreated patients was significantly reduced (p50.004) compared to untreated allergics. These decreases in local nasal inhibitory activity paralleled reductions in serum inhibitory activity after SLIT (p50.03). Interestingly, the magnitude of this suppression was more profound with local antibodies (45%) compared to the peripheral antibody responses (35%). CONCLUSIONS: For the first time, IgG4 antibodies with inhibitory activity for IgE-FAB were measured in the nasal fluid of SLIT treated patients. Local IgG4 antibodies may potentially be used as a surrogate/ predictive biomarker for monitoring SLIT.