Broad IgG repertoire in patients with chronic rhinosinusitis with nasal polyps regulates proinflammatory IgE responses

Orchestration of immunoglobulin isotypes, subclasses, and specificities in patients receiving intravenous IgG or subcutaneous immunotherapy and those with chronic rhinosinusitis with nasal polyps: Toward precision medicine

“…Thus the switched IgE 1 B cells inherit the specificity of their IgG precursors, which earlier underwent somatic hypermutation and affinity maturation in the immune response (Fig 1). 9 In line with a recent study of local antibody repertoires in patients with allergic rhinitis, 10 Shamji et al 3 report extensive sharing of clonal signatures between IgG and IgE repertoires, although this has not yet been nailed down to the actual specificities. The results nevertheless suggest the potential capacity of the IgG to compete with IgE for antigen.…”

“…It is well established that local IgE antibodies in nasal polyp tissue are functionally active and capable of eliciting mast cell activation in an antigen-specific manner. 8 Shamji et al 3 demonstrated that this activity might be regulated by competition between IgG and IgE antibodies of the same specificity. They preformed mixture of a grass pollen extract or Staphylococcus aureus enterotoxin B with homogenates from the nasal polyps of patients with CRSwNP containing IgE antibodies specific for the respective antigens provoked T-cell proliferation and basophil activation with histamine release.…”

“…Although coexpression of the 2 antibodies would suppress inflammation, later switching to IgE might lead to development or aggravation of CRSwNP. Shamji et al 3 propose that recombinant antigenspecific IgG antibodies derived from identified allergen-specific IgE V-region sequences could be used in the passive immunization of patients exposed to potentially dangerous antigens. Experiments with recombinant antibodies against S aureus enterotoxins 6 have demonstrated proof of principle.…”

“…A common principle is illustrated in several different approaches to treating inflammatory disease reported in 3 recent articles published in the Journal: (1) intravenous IgG (IVIG) treatment in patients with autoimmune disease, 1 (2) subcutaneous immunotherapy (SCIT) in patients with grass pollen-induced allergic rhinitis, 2 and (3) anti-IgE injections in patients with chronic rhinosinusitis with nasal polyps (CRSwNP) targeting IgE. 3 In each of these studies, IgE is the immediate cause of the inflammation, irrespective of whether it acts as an antibody or an antigen, and the therapy depends on the ability of IgG to interfere with the activity of the IgE. This review briefly summarizes the evidence in these articles for the interplay between the different isotypes and clinical relevance.…”

<p>The Role of Mast Cells in Aspirin-Exacerbated Respiratory Disease (AERD) Pathogenesis: Implications for Future Therapeutics</p>

“…Polyp IgE has been demonstrated to be functional and induces basophil activation with histamine release and upregulation of the surface marker CD63. 14 The effects of nasal polyp IgE specifically on FcεRI responses in MCs are yet to be elucidated.…”