Neglected roles of IgG Fc-binding protein secreted from airway mucin-producing cells in protecting against SARS-CoV-2 infection

Both innate immunity and acquired immunity are involved in severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection. The induction of Abs that neutralize the virus has been described, and certain Abs against endemic coronaviruses may cross-react with SARS-CoV-2. Detailed mechanisms to protect against the pandemic of SARS-CoV-2 remain unresolved. We previously reported that IgG Fc-binding protein (Fcγbp), a unique, large molecular weight, and mucin-like secretory Fc receptor protein, secreted from goblet cells of human small and large intestine, mediates the transportation of serum IgG onto the mucosal surface. In this review, we show that mucous bronchial gland cells and some goblet cells are immunoreactive for Fcγbp. Fcγbp traps the cross-reactive (both neutralizing and non-neutralizing) IgG bound to the virus and can consequently eliminate the virus from the mucosal surface to decrease viral loads. Fcγbp can also suppress immune overreaction by interfering with Fc-binding by macrophages and competing with complement fixation. Fcγbp secreted from mucin-producing cells of the airway functions as an important anti-infection mucosal defense. The Fcγbp-mediated mechanism can be a key factor in explaining why SARS-CoV-2 is less infective/lethal in children, and may also be involved in the unique Ab response, recurrent infection, and effects of serum therapy and vaccination.

Bronchial Carcinoids and Bronchial Gland Carcinomas

Bronchial carcinoid and bronchial gland carcinomas are rare airway-related thoracic malignancies. Carcinoid is a neuroendocrine neoplasm and comprises 1-2 % of primary lung cancers. Affected patients are younger than those with lung cancer, and may present with signs and symptoms of airway obstruction including cough, hemoptysis, wheezing, and recurrent pulmonary infection. Carcinoid typically manifests as a central nodule or mass and may cause post obstructive atelectasis or pneumonia. On imaging these lesions are usually well marginated pulmonary nodules or masses and may be completely endobronchial, partially endobronchial or may abut an airway. Typical carcinoid often exhibits an indolent behavior and carries a good prognosis with complete surgical excision. Atypical carcinoid is similar to typical carcinoid on imaging but has a more aggressive behavior and may be associated with metastatic intrathoracic lymphadenopathy. Bronchial gland carcinomas include adenoid cystic carcinoma (ACC) and mucoepidermoid carcinoma (MEC). ACC is the second most common primary tracheal malignancy and manifests as an endoluminal tracheal nodule or as circumferential tracheal narrowing. MEC typically affects segmental bronchi and may be indistinguishable from carcinoid on imaging. Although these lesions may exhibit an indolent course, they are locally invasive malignancies, and affected patients have a variable prognosis.