The Role of IgA in Chronic Upper Airway Disease: Friend or Foe?

Abstract

Chronic upper airway inflammation is amongst the most prevalent chronic disease entities in the Western world with prevalence around 30% (rhinitis) and 11% (rhinosinusitis). Chronic rhinitis and rhinosinusitis may severely impair the quality of life, leading to a significant socio-economic burden. It becomes more and more clear that the respiratory mucosa which forms a physiological as well as chemical barrier for inhaled particles, plays a key role in maintaining homeostasis and driving disease. In a healthy state, the mucosal immune system provides protection against pathogens as well as maintains a tolerance toward non-harmful commensal microbes and benign environmental substances such as allergens. One of the most important players of the mucosal immune system is immunoglobulin (Ig) A, which is well-studied in gut research where it has emerged as a key factor in creating tolerance to potential food allergens and maintaining a healthy microbiome. Although, it is very likely that IgA plays a similar role at the level of the respiratory epithelium, very little research has been performed on the role of this protein in the airways, especially in chronic upper airway diseases. This review summarizes what is known about IgA in upper airway homeostasis, as well as in rhinitis and rhinosinusitis, including current and possible new treatments that may interfere with the IgA system. By doing so, we identify unmet needs in exploring the different roles of IgA in the upper airways required to find new biomarkers or therapeutic options for treating chronic rhinitis and rhinosinusitis.

A new hope? Possibilities of therapeutic IgA antibodies in the treatment of inflammatory lung diseases

“…Low or absent IgA levels are a relatively common clinical observation, often caused by selective IgA deficiency (sIgAD) the most common type of primary antibody deficiency. Although most of these patients are asymptomatic, the lack of IgA antibodies results in a notable number of patients (~40% of all sIgAD patients) with several immunological disorders (24,25). The most common disorders, associated with low IgA levels are recurrent respiratory infections, allergic conditions, gastrointestinal disorders or auto-immune diseases (24-30), highlighting the important role of IgA in mucosal areas.…”

“…Alterations in IgA-mediated mucosal immunity and impaired IgA functions that have been correlated with the most common inflammatory lung diseases are summarized in Table 1 . The important role of IgA in the mucosal immunity is also demonstrated indirectly by the ability of virulent bacterial strains to produce anti-IgA or anti-FcαRI proteins which help the pathogen to evade IgA-mediated immune responses ( 26 , 51 ).…”

IgA-producing B cells in lung homeostasis and disease

“…Few data exist on the role of IgA and IgA-producing B cells in sinonasal diseases (163). In patients with selective IgAD, 48-78% display recurrent upper airway infections, including rhinitis and rhinosinusitis (164)(165)(166), likely due to the major role of IgA against viral infections (167).…”

Biofilm aggregates and the host airway-microbial interface

“…Secretory immunoglobulin A (S-IgA) produced by plasma (immunoglobulin secreting cells) lining the airway epithelium is the major immunoglobulin component of human mucosal surfaces and contributes to preventing pathogen adherence and promoting clearance in the airway. While less studied in the respiratory tract compared to the gut mucosa, IgA appears to be important in homeostasis and controlling inflammation ( Sánchez Montalvo et al., 2022 ). IgA is produced as a dimer and transcytosed from the basal epithelial side to the apical surface by the polymeric immunoglobulin receptor (pIgR) to form S-IgA, which functions to neutralize many viral pathogens and some bacteria and with airway mucus play a role in agglutinating microorganisms ( Gohy et al., 2014 ; de Fays et al., 2022 ).…”

“…This study suggests that bacterial aggregates may be a default bacterial mode of growth in some infection sites. S-IgA may also contribute to passive agglutination of airway bacteria, although its role remains largely unexplored ( Sánchez Montalvo et al., 2022 ). Importantly, aggregated bacteria were more tolerant to killing by antibiotics .…”