The mucosa-kidney axis in IgA nephropathy

Area of Science:

• Nephrology
• Immunology
• Gastroenterology

Background:

• The connection between IgA nephropathy (IgAN) and mucosal immunity, particularly the gastrointestinal tract, has been observed since the 1970s.
• Visible hematuria triggered by infections and associations with conditions like celiac disease suggest a mucosa-kidney axis in IgAN pathogenesis.

Purpose of the Study:

• To review current evidence linking the gastrointestinal mucosa, bone marrow-derived IgA, and IgA nephropathy.
• To explore the role of mucosal integrity, immune responses to mucosal antigens, and reactivity to dietary proteins in IgAN.

Main Methods:

• Review of existing literature and genetic studies, including genome-wide association studies (GWAS).
• Analysis of systemic immune responses to mucosal antigens and patient reactivity to dietary proteins.
• Examination of associations between IgAN and gastrointestinal diseases.

Main Results:

• GWAS identified IgAN risk loci in genes related to intestinal mucosal integrity and immune networks.
• Increased systemic immune response to mucosal antigens and heightened reactivity to dietary proteins in IgAN patients.
• Uncertainty remains regarding shared pathogenesis or exacerbation of IgAN by gastrointestinal diseases.

Conclusions:

• The gastrointestinal mucosa and IgA production are implicated in IgAN.
• Mucosal alterations, such as infections, may activate innate immunity and exacerbate IgAN.
• Clinical interventions targeting mucosal mechanisms have shown inconsistent results, with ongoing trials anticipated.