Serum IgA Fc effector functions in infectious disease and cancer

Abstract

Immunoglobulin (Ig) A is the most abundant antibody isotype present at mucosal surfaces and the second most abundant in human serum. In addition to preventing pathogen entry at mucosal surfaces, IgA can control and eradicate bacterial and viral infections through a variety of antibody-mediated innate effector cell mechanisms. The role of mucosal IgA in infection (e.g. neutralization) and in inflammatory homeostasis (e.g. allergy and autoimmunity) has been extensively investigated; by contrast, serum IgA is comparatively understudied. IgA binding to fragment crystallizable alpha receptor plays a dual role in the activation and inhibition of innate effector cell functions. Mounting evidence suggests that serum IgA induces potent effector functions against various bacterial and some viral infections including Neisseria meningitidis and rotavirus. Furthermore, in the era of immunotherapy, serum IgA provides an interesting alternative to classical IgG monoclonal antibodies to treat cancer and infectious pathogens. Here we discuss the role of serum IgA in infectious diseases with reference to bacterial and viral infections and the potential for IgA as a monoclonal antibody therapy.

Effects of α-glyceryl monolaurate on growth, immune function, volatile fatty acids, and gut microbiota in broiler chickens

“…Our study demonstrates that adding α-GML increases IgM and IgY levels in broilers compared with broilers in the NCO group. IgA plays an important role in preventing the invasion of pathogens, such as bacteria and viruses, through a variety of antibody-mediated innate effector cell mechanisms ( Pabst, 2012 ; Davis et al., 2020 ). IgA levels increase when the body is under stress or subject to bacterial infection, and so on ( Pabst, 2012 ; Bunker and Bendelac, 2018 ; Wilmore et al., 2018 ), and changes in IgA levels were associated with intestinal flora ( Macpherson et al., 2018 ; Beller et al., 2020 ; Suzuki, 2020 ).…”

IgA Vasculitis: Etiology, Treatment, Biomarkers and Epigenetic Changes

“…FcαRI is a receptor for IgA and this signal has a bifunctional action in both proinflammatory and anti-inflammatory effects [ 44 , 45 , 46 ]. FcαRI is expressed on monocytes, macrophages, intestinal dendritic cells, and Kupffer cells [ 46 ]. The induction of FcαRI signaling is associated with the immunoreceptor tyrosine-based activation motif (ITAM).…”

IgA and FcαRI: Versatile Players in Homeostasis, Infection, and Autoimmunity

“…12 Pathogen-specific IgA is found at mucosal surfaces and in circulation during several infectious diseases, while the exact function of IgA remains unclear. 6,11 Passive immunity (via neutralization) as well as immune activating properties of IgA have been described for infections in the respiratory-and reproductive tracts such as Mycobacterium tuberculosis (Mtb), HIV-1, and more recently severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections. [126][127][128] Passive Immunity…”

“…9 By contrast, IgA immune complexes (eg, IgA-opsonized bacteria) induce pro-inflammatory responses by cross-linking of FcαRI, which is important in controlling infections ( Figure 1B). 10,11 The presence of excessive IgA immune complexes or IgA-opsonized bacteria can however lead to uncontrolled and disproportionate FcαRI-mediated immune cell activation, resulting into severe tissue damage as observed during chronic inflammation and autoimmunity. 12 Increased serum IgA levels or IgA autoantibodies have been reported in multiple diseases including rheumatoid arthritis, IgA nephropathy, IgA vasculitis, dermatitis herpetiformis, celiac disease, inflammatory bowel disease, Sjögren's syndrome, ankylosing spondylitis, alcoholic liver cirrhosis, and acquired immunodeficiency syndrome.…”