BACKGROUND: Induction of allergen-specific IgG(4) antibodies is the most consistent immunological finding in immunotherapy trials. However, quantitative assessments of IgG(4) antibodies have not proven beneficial in evaluating clinical changes during or after immunotherapy. In the current study, we investigated the relationship between clinical outcome and allergen-specific IgG(4) titres or functional antibody responses following immunotherapy. We hypothesized that functional assays of serum IgG-associated inhibitory activity such as inhibition of IgE-allergen interactions (IgE-blocking factor) and inhibition of CD23-dependent IgE-facilitated allergen binding (IgE-FAB) correlate more closely with clinical outcome and may be biomarkers of clinical response. METHODS: In an 8-month dose-response randomized double-blind placebo-controlled study, 221 polysensitized subjects with severe seasonal rhinitis received Alutard SQ, Phleum pratense 100,000 SQ-U, 10,000 SQ-U or placebo injections. Serum specimens were collected before treatment, after up-dosing, during the peak season and at the end of the study. Allergen-specific IgG(4) titres and IgG-associated inhibitory activity were evaluated. RESULTS: A time- and dose-dependent increase in serum inhibitory activity for both the IgE-blocking factor and IgE-FAB was observed, which paralleled increases in grass pollen-specific IgG(4) antibodies. A modest but significant inverse relationship was demonstrated between postimmunotherapy serum inhibitory activity and combined symptom-rescue medication scores (IgE-FAB: r = -0.25, P = 0.0002; IgE-blocking factor: r = -0.28, P < 0.0001), whereas this was not observed for immunoreactive IgG(4) levels (r = -0.11, P = 0.12). CONCLUSIONS: Functional assays of inhibitory IgG(4) and IgE-blocking factor may be more useful surrogates of clinical response than IgG(4). Whether these antibody effects may serve as predictive biomarkers of clinical efficacy in individual patients requires further investigation.
BACKGROUND: Induction of allergen-specific IgG(4) antibodies is the most consistent immunological finding in immunotherapy trials. However, quantitative assessments of IgG(4) antibodies have not proven beneficial in evaluating clinical changes during or after immunotherapy. In the current study, we investigated the relationship between clinical outcome and allergen-specific IgG(4) titres or functional antibody responses following immunotherapy. We hypothesized that functional assays of serum IgG-associated inhibitory activity such as inhibition of IgE-allergen interactions (IgE-blocking factor) and inhibition of CD23-dependent IgE-facilitated allergen binding (IgE-FAB) correlate more closely with clinical outcome and may be biomarkers of clinical response. METHODS: In an 8-month dose-response randomized double-blind placebo-controlled study, 221 polysensitized subjects with severe seasonal rhinitis received Alutard SQ, Phleum pratense 100,000 SQ-U, 10,000 SQ-U or placebo injections. Serum specimens were collected before treatment, after up-dosing, during the peak season and at the end of the study. Allergen-specific IgG(4) titres and IgG-associated inhibitory activity were evaluated. RESULTS: A time- and dose-dependent increase in serum inhibitory activity for both the IgE-blocking factor and IgE-FAB was observed, which paralleled increases in grass pollen-specific IgG(4) antibodies. A modest but significant inverse relationship was demonstrated between postimmunotherapy serum inhibitory activity and combined symptom-rescue medication scores (IgE-FAB: r = -0.25, P = 0.0002; IgE-blocking factor: r = -0.28, P < 0.0001), whereas this was not observed for immunoreactive IgG(4) levels (r = -0.11, P = 0.12). CONCLUSIONS: Functional assays of inhibitory IgG(4) and IgE-blocking factor may be more useful surrogates of clinical response than IgG(4). Whether these antibody effects may serve as predictive biomarkers of clinical efficacy in individual patients requires further investigation.
Authors: Guy W Scadding; Moises A Calderon; Mohamed H Shamji; Aarif O Eifan; Martin Penagos; Florentina Dumitru; Michelle L Sever; Henry T Bahnson; Kaitie Lawson; Kristina M Harris; Audrey G Plough; Joy Laurienzo Panza; Tielin Qin; Noha Lim; Nadia K Tchao; Alkis Togias; Stephen R Durham Journal: JAMA Date: 2017-02-14 Impact factor: 56.272
Authors: Lowiek M Hubers; Lucas J Maillette de Buy Wenniger; Marieke E Doorenspleet; Paul L Klarenbeek; Joanne Verheij; Erik A Rauws; Thomas M van Gulik; Ronald P J Oude Elferink; Stan F J van de Graaf; Niek de Vries; Ulrich Beuers Journal: Clin Rev Allergy Immunol Date: 2015-06 Impact factor: 8.667
Authors: Amedee Renand; Mohamed H Shamji; Kristina M Harris; Tielin Qin; Erik Wambre; Guy W Scadding; Peter A Wurtzen; Stephen J Till; Alkis Togias; Gerald T Nepom; William W Kwok; Stephen R Durham Journal: J Allergy Clin Immunol Date: 2017-11-09 Impact factor: 10.793
Authors: Jörg Kleine-Tebbe; Mikkel Walmar; Klaus Bitsch-Jensen; Elke Decot; Oliver Pfaar; Dolores Hernández Fernández de Rojas; Fernando Rodriguez Journal: Clin Drug Investig Date: 2014-08 Impact factor: 2.859