Anti-IgE IgG autoantibodies isolated from therapeutic normal IgG intravenous immunoglobulin induce basophil activation

摘要

Basophils are rare granulocytes.Despite representing only~0.5%of all leukocytes,basophils have several important physiological functions.1,2 Although basophils lack the classic features of professional antigen-presenting cells,3–7 through the secretion of cytokines,they orient the immune response by polarizing Th2 differentiation and supporting B-cell differentiation and class switching.Basophils are also critical for mediating protection against helminth infection.1,2,8,9 Basophils receive activation signals from diverse sources.It is well recognized that cytokines such as IL-3,granulocyte–macrophage colony-stimulating factor(GM-CSF),thymic stromal lymphopoietin(TSLP)and IL-33;various toll-like receptor ligands;allergen-bound IgE provide activation signals to basophils and induce the release of inflammatory mediators.10–15 In addition,several reports have also demonstrated the existence of anti-IgE autoantibodies that possess the capacity to induce basophil activation in patients with chronic spontaneous urticaria(CSU),atopic or non-atopic asthma or autoimmune disease.16–21 However,isolation and functional exploration of such anti-IgE IgG autoantibodies from either healthy donors or patients have not been attempted yet.By using a pooled normal IgG preparation from healthy donors,specifically intravenous immunoglobulin G(IVIG)22 that represents the complete IgG repertoire of a normal individual,we attempted to address this outstanding question in the field.