Protective immunity is converted to allergy in patients with chronic rhinosinusitis with nasal polyposis
Published online: July 24, 2018
CRSwNP (chronic rhinosinusitis with nasal polyposis) is characterized by local IgE production, eosinophilic inflammation and polyposis at the nose and paranasal sinus. Nasal polyps often obstruct airflow and lead to loss of the sense of smell. Corticosteroids and surgery are the first line treatment for CRSwNP. However, polyposis frequently recurs after surgery. Previous studies have suggested that bacterial superantigens may contribute to the pathogenesis of CRSwNP. It has been unclear whether specific antigens trigger CRSwNP.
In a recent study published in The Journal of Allergy & Clinical Immunology (JACI), Takeda and colleagues provided new insight into the pathogenesis of CRSwNP by characterizing IgE produced in NPs. In the study, the researchers generated a panel of monoclonal antibodies derived from IgE-producing cells in NPs to determine their reactive antigens (allergens). They also analyzed immunoglobulin genes expressed in NPs by next-generation sequencing and characterized associated lymphocytes by flow cytometry to elucidate the development pathway of IgE-secreting plasmablasts in NPs.
The study found that about 20% of tested antibodies specifically recognized nasal bacteria, including Staphylococcus aureus, Streptococcus pyogenes, and Haemophilus influenzae. These antibacterial IgE antibodies were highly mutated, implying that antigen-specific, type-2 (Th2) immune reaction occurs in the disease. The study showed enhanced Th2 response against S pyogenes in cultured peripheral blood mononuclear cells from CRSwNP patients. The next-generation sequencing revealed that IgE repertoires in NPs were oligoclonal and frequently shared their variable sequences with IgG and IgA, but not with IgM. IgE in NPs is inferred to be a product of antigen-specific responses and share reactivity with local IgG and IgA antibodies. The study also performed flow cytometric analysis, which detected surface IgE expression on germinal center B cell and plasmablast subsets, but not on memory B cells in NPs. These findings indicated that IgE class-switching may take place in ectopic germinal centers, and the resultant cells differentiate into IgE-secreting plasmablasts in NPs.
Overall, the study suggests that allergic conversion of the mucosal response against nasal bacteria underlies the pathogenesis of CRSwNP. The study demonstrated that nasal bacteria are candidate causative allergens of CRSwNP. Antibacterial treatments including oral antibiotics and nasal irrigation would be considered an important option for patients with CRSwNP, in particular for the recurrence prevention after surgery. The identified bacterial antigens in the study might be applicable to not only diagnosis but also non-steroid therapy, such as desensitization. As CRSwNP is tightly linked to asthma, these findings could help to understand the underlying mechanisms in other allergic diseases as well.
The Journal of Allergy and Clinical Immunology (JACI) is the official scientific journal of the AAAAI, and is the most-cited journal in the field of allergy and clinical immunology.
Allergic conversion of protective mucosal immunity against nasal bacteria in chronic rhinosinusitis with nasal polyposis by Kazuya Takeda, MD, Hitoshi Kikutani, MD, PhD, Shuhei Sakakibara, PhD