Genome-wide association studies in patients with IgA nephropathy (IgAN) have identified risk loci in genes involved in the intestinal mucosal integrity and immune network
Immune responses to mucosal antigens and immunization studies suggest that the systemic response to mucosal antigens is exaggerated in patients with IgAN
Patients with IgAN have increased reactivity to dietary proteins associated with subclinical intestinal mucosal inflammation, although in general they do not have overt dietary intolerance
Very rarely, IgAN is associated with gastrointestinal diseases; whether these diseases indeed share a common pathogenesis or whether gastrointestinal inflammation exacerbates IgAN is uncertain
Mucosal alterations such as respiratory tract infections could activate the innate immune system, aggravate a pre-existing IgAN and promote disease manifestations such as macrohaematuria, rather than a share a pathogenetic link with IgAN
Intervention studies targeting the mucosae in IgAN have been inconclusive so far, but new studies are ongoing
Links between IgA nephropathy (IgAN) and the mucosa have been recognized since the 1970s. In particular, the observation of visible haematuria induced by respiratory infections in patients with IgAN and the association of IgAN with diseases in which the mucosa plays a part, especially coeliac disease, have been taken as evidence of a mucosa–kidney axis. Here, we review current evidence that links the mucosa, in particular the gastrointestinal mucosa, and IgA produced by the bone marrow with IgAN. Genome-wide association studies in patients with IgAN have identified risk loci in genes involved in the intestinal mucosal integrity and immune network. Furthermore, the systemic immune response to mucosal antigens in IgAN is increased. Moreover, patients with IgAN have an increased reactivity to dietary proteins associated with subclinical intestinal mucosal inflammation. Associations between IgAN and gastrointestinal diseases have also been reported in a small number of patients, but whether these diseases share a common pathogenesis or whether gastrointestinal inflammation exacerbates IgAN is uncertain. Indeed, mucosal alterations such as infections could activate the innate immune system, aggravate a pre-existing IgAN and promote disease manifestations such as macrohaematuria. Various clinical interventions and trials targeting the mucosa or presumed mucosa-associated mechanisms have so far not yielded consistent findings and the results of ongoing trials are eagerly awaited.
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J. Floege has received honoraria from Pharmalink, Sweden. J. Feehally declares no competing interests.
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Floege, J., Feehally, J. The mucosa–kidney axis in IgA nephropathy. Nat Rev Nephrol 12, 147–156 (2016). https://doi.org/10.1038/nrneph.2015.208
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