Increased Prevalence of Anti-Gliadin IgA-Antibodies with Aberrant Duodenal Histopathological Findings in Patients with IgA-Nephropathy and Related Disorders

Almroth, Gabriel; Axelsson, Thiane Gama; Müssener, E.; Grodzinsky, Ewa; Midhagen, Gunnar; Olcén, Per

doi:10.3109/2000-1967-060

Cited by 12 publications

(12 citation statements)

References 37 publications

(54 reference statements)

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“…Other studies, by contrast, described circulating IgA antigliadin antibodies in up to 50% of patients with IgAN, compared with 0% in controls 29,76,77 . However, anti reticulin and/or antiendomysial antibodies, which are characteristic of coeliac disease, were not detected in patient or control sera in most studies [76][77][78][79] .…”

Section: Coeliac Diseasementioning

confidence: 84%

“…However, anti reticulin and/or antiendomysial antibodies, which are characteristic of coeliac disease, were not detected in patient or control sera in most studies [76][77][78][79] . Only a single paper described the presence of IgG antiendomysial antibodies in ~40% of patients with IgAN 80 .…”

Section: Coeliac Diseasementioning

confidence: 99%

“…Only a single paper described the presence of IgG antiendomysial antibodies in ~40% of patients with IgAN 80 . Small-bowel biopsies in seven patients with IgAN who tested positive for antibodies against gliadin were pathologic in three cases and two patients exhibited infiltrating lymphocytes on the surface of the intestinal lining (Marsh class I in the classification of coeliac disease) 77 . However, higher Marsh classes, in particular those characterized by villous atrophy typical of coeliac disease (FIG.…”

Section: Coeliac Diseasementioning

confidence: 99%

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The mucosa–kidney axis in IgA nephropathy

2015

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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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Section: Coeliac Diseasementioning

confidence: 84%

Section: Coeliac Diseasementioning

confidence: 99%

Section: Coeliac Diseasementioning

confidence: 99%

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The mucosa–kidney axis in IgA nephropathy

2015

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“… 57 Patients with IgAN show dysbiosis characterized by altered composition of the main bacterial phyla ( Firmicutes , Bacteroidetes , Proteobacteria and Actinobacteria ) compared with healthy subjects, with a decrease in total anaerobic bacteria densities ( Clostridium , Enterococcus , Lactobacillus , Leuconostoc and Bifidobacterium ) 53 . In contrast, patients with primary and secondary IgAN showed altered duodenal histopathological findings and increased intestinal permeability 58 . Constant exposure to endotoxins induced epithelial cells to secrete B‐cell‐activating factor of the tumor necrosis factor family (BAFF) and the proliferation‐inducing ligand (APRIL), both related to the maintenance of tolerogenic immune responses to the microbiota.…”

Section: Dysbiosis and Iga Nephropathymentioning

confidence: 99%

“…53 In contrast, patients with primary and secondary IgAN showed altered duodenal histopathological findings and increased intestinal permeability. 58 Constant exposure to endotoxins induced epithelial cells to secrete B-cell-activating factor of the tumor necrosis factor family (BAFF) and the proliferationinducing ligand (APRIL), both related to the maintenance of tolerogenic immune responses to the microbiota. Mice overexpressing BAFF (BAFF-Tg) have shown high levels of aberrantly glycosylated serum polymeric IgA and, consequently, IgA mesangial deposition.…”

Section: Dysbiosis and Iga Nephropathymentioning

confidence: 99%

The microbiota and chronic kidney diseases: a double‐edged sword

et al. 2016

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Recent findings regarding the influence of the microbiota in many inflammatory processes have provided a new way to treat diseases. Now, one may hypothesize that the origin of a plethora of diseases is related to the health of the gut microbiota and its delicate, although complex, interface with the epithelial and immune systems. The ‘westernization' of diets, for example, is associated with alterations in the gut microbiota. Such alterations have been found to correlate directly with the increased incidence of diabetes and hypertension, the main causes of chronic kidney diseases (CKDs), which, in turn, have a high estimated prevalence. Indeed, data have arisen showing that the progression of kidney diseases is strictly related to the composition of the microbiota. Alterations in the gut microbiota diversity during CKDs do not only have the potential to exacerbate renal injury but may also contribute to the development of associated comorbidities, such as cardiovascular diseases and insulin resistance. In this review, we discuss how dysbiosis through alterations in the gut barrier and the consequent activation of immune system could intensify the progression of CKD and vice versa, how CKDs can modify the gut microbiota diversity and abundance.

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The gut–kidney axis in IgA nephropathy: role of microbiota and diet on genetic predisposition

Coppo

2017

Pediatr Nephrol

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Recent data suggest that gut-associated lymphoid tissue (GALT) plays a major role in the development of immunoglobulin A (IgA) nephropathy (IgAN). A genome-wide association study showed that most loci associated with the risk of IgAN are also associated with immune-mediated inflammatory bowel diseases, maintenance of the intestinal barrier and regulation of response to gut pathogens. Studies involving experimental models have demonstrated a pivotal role of intestinal microbiota in the development of IgAN in mice producing high levels of IgA and in transgenic mice overexpressing BAFF, a B-cell factor crucial for IgA synthesis, indicating the role of genetic background, B-cell activity, GALT intestinal immunity and diet. The effect of diet was suggested by pilot studies carried out 30 years ago which showed that a gluten-rich diet induced IgAN in mice and that some patients benefited from a gluten-free diet. A recent experimental model in mice expressing human IgA1 and Fc alpha receptor CD89 reported clinical and histological improvement after a gluten-free diet. Clinical observations have elicited new interest in GALT hyper-reactivity in IgAN patients. In a pilot study, a reduction in proteinuria was attained using an enteric controlled-release formulation of the corticosteroid budesonide targeted to the Peyer's patches at the ileocecal junction. This formulation was tested in the placebo-controlled NEFIGAN phase 2b trial, with a reduction in proteinuria after 9 months of treatment together with stabilization of renal function in patients with persistent proteinuria. In conclusion, the gut-kidney axis modulated by microbiota and diet is a promising target for focused treatment of IgAN in genetically predisposed patients at risk of progression.

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Increased Prevalence of Anti-Gliadin IgA-Antibodies with Aberrant Duodenal Histopathological Findings in Patients with IgA-Nephropathy and Related Disorders

Cited by 12 publications

References 37 publications

The mucosa–kidney axis in IgA nephropathy

The mucosa–kidney axis in IgA nephropathy

The microbiota and chronic kidney diseases: a double‐edged sword

The gut–kidney axis in IgA nephropathy: role of microbiota and diet on genetic predisposition

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