High IgG4 antibody level is associated with failure of immunotherapy with inhalant allergens

Abstract

Summary We have analysed all available data on the relationship between IgG4 Ab level and clinical effect of immunotherapy (IT) with inhalant allergens. The data from three of the seven independent studies could, without reservations, be analysed by a joint statistical analysis. We found that late high IgG4 Ab level, measured at the end of IT, was strongly associated with treatment failure (P= 6.54 ± 105; n= 67). The ratio of risks for treatment success in the group with late low IgG4 Ab level was 1.82, whereas the ratio of risks for treatment failure in the group with late high IgG4 Ab level was 11.4. The data from a fourth, presumably comparable, study further supported the existence of an association between high IgG4 Ab level and treatment failure. In contrast, two other studies found that high mean IgG4 Ab level was associated with good clinical response. Possible reasons for this apparent discrepancy are discussed. We also found that early high IgG4 Ab level, measured within 3 months after initiation of IT, was strongly associated with treatment failure after 1–2 years of IT (P= 1.05 ± 10−4; n= 30). The sensitivity and specificity of early high IgG4 Ab level as indicator for treatment failure was 100% and 83%, respectively. At the prevalences found in the present study, the predictive value of early high IgG4 Ab level for treatment failure was 0.6, whereas the predictive value of early low IgG4 Ab level for treatment success was 1.00.

The IgE-facilitated allergen binding (FAB) assay: Validation of a novel flow-cytometric based method for the detection of inhibitory antibody responses

“…Patients receiving allergen-specific immunotherapy have been shown to have increased concentrations of allergen-specific IgG4 antibodies in their serum (Gehlhar et al, 1999;Jutel et al, 2003;Nouri-Aria et al, 2004;Djurup et al, 1987). However assays that detect only immunoreactive IgG4 are unlikely to predict clinical efficacy (Djurup et al, 1987;Muller et al, 1989;Ewan et al, 1993;Bodtger et al 2005).…”

“…However assays that detect only immunoreactive IgG4 are unlikely to predict clinical efficacy (Djurup et al, 1987;Muller et al, 1989;Ewan et al, 1993;Bodtger et al 2005). Therefore, measuring IgG4 concentration is not suitable for monitoring clinical efficacy of immunotherapy.…”

Ten‐Year Follow‐Up Study of Allergen‐Specific Immunoglobulin E and Immunoglobulin G4, Soluble Interleukin‐2 Receptor, Interleukin‐4, Soluble Intercellular Adhesion Molecule‐1 and Soluble Vascular Cell Adhesion Molecule‐1 in Serum of Patients on Immunotherapy for Perennial Allergic Rhinitis

“…The original aim of this prospective study was therefore to investigate the time-course changes in specific IgE and specific IgG4 for a span of 10 years in serum of both untreated and immunotherapy patients with perennial allergic rhinitis. However, changes in specific antibodies in serum were subsequently considered to represent an epiphenomenon unrelated to the working mechanisms of immunotherapy, because the changes had no relationship to the clinical response in several studies [6,7].…”

“…Some authors claimed that an elevation of specific IgG4 contributed to the clinical efficacy of immunotherapy [4,5,26]. By contrast, others argued that specific IgG4 might not play a clinical role in immunotherapy but be simply a marker of antigen exposure following subcutaneous injections, because they could not confirm any causal relationship between the clinical effect and an increase in specific IgG4 in serum [6,7]. To discuss correctly the possible clinical importance of specific IgG4 in the mechanisms of action of immunotherapy, we should require the serial monitoring of specific IgG4 for considerable years of immunotherapy, and the possible correlation between the time-course…”

“…Allergen-specific immunoglobulin (Ig)E and IgG, especially the blocking antibody of IgG4, were previously believed to be of key importance in allergic rhinitis, and considerable attention was devoted for decades to the role of specific IgE and IgG4 in serum relation to clinical outcome. However, there is no definite conclusion regarding these antibodies, because an increase in specific IgG4 was associated with a good clinical efficacy of immunotherapy in some studies [4,5] whereas this association was not confirmed in others [6,7].…”