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

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 x 10(5); 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 x 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.