Primary IgA Nephropathy: The Relevance of Experimental Models in the Understanding of Human Disease

Montinaro, Vincenzo; Gesualdo, Loreto; Schena, Francesco Paolo

doi:10.1159/000187084

Cited by 10 publications

(6 citation statements)

References 41 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Later, frequent reports of IgA NP in patients with syndromes affecting IgA secretory epithelium in gut and respiratory tract suggest that, in at least some patients, at a certain disease stage the antibody is produced as a part of a specific host immune response to a variety of offending antigens in these areas. Dose as well as composition of the antigen are expected to vary according to its origin which is confirmed experimentally [17], but no data exist about the composition of the antigen in human IgA NP. Evolutional analyses of a chronic model of IgA NP [18] have shown intense histopathological changes during the disease progression which were sustainable only by continuous deposition of nephritogenic IgA immune complexes.…”

Section: Discussionmentioning

confidence: 99%

IgA-Antigliadin Antibodies in Patients with IgA Nephropathy: The Secondary Phenomenon?

Ots¹,

Uibo²,

Metsküla

et al. 1999

Am J Nephrol

View full text Add to dashboard Cite

Circulating IgA-antigliadin antibodies (IgA-AGA) are often found in patients with IgA nephropathy (NP). IgA-AGA are sensitive markers of an abnormal immune system reaction to gluten, seen particularly in patients with celiac disease. However, a lack of IgA-antireticulin and IgA-antiendomysium antibodies and often jejunal mucosal atrophy of patients with IgA NP suggest that most patients do not have latent celiac disease. To examine the relationship between IgA-AGA and clinical data, enzyme-linked immunosorbent assays for IgA-AGA were performed in 28 patients with IgA NP and in 50 healthy persons. The results were calculated in arbitrary units (AU). The cutoff level for a negative or a positive test was found to be 60 AU, calculated according to the AGA test result (mean + 3 SD) in 50 healthy persons. The following clinical data were assessed: age, gender, disease duration, daily proteinuria, blood pressure, serum creatinine, and creatinine clearance. Control sera were negative for IgA-AGA. Positive IgA-AGA tests were observed in 14 of the 28 patients (p < 0.0001 vs. controls) and high levels of IgA-AGA (AU >90) in 6 of the 28 patients (p < 0.001 vs. controls). The mean duration of the disease of the patients with positive IgA-AGA was significantly longer as compared with the patients who had a negative antibody test. IgA-AGA correlated with age (p < 0.05, r = 0.56), disease duration (p < 0.05, r = 0.40), and blood pressure (p < 0.05, r = 0.48). Antireticulin and antiendomysium antibody tests were negative in all patient and control sera. We conclude that IgA-AGA are associated with the progression of IgA NP. Our findings support the current concept about the pathogenesis of IgA NP, where the defective IgA production itself may be the primary and intestinal lesions as well as the production of IgA-AGA the secondary phenomenon.

show abstract

Section: Discussionmentioning

confidence: 99%

IgA-Antigliadin Antibodies in Patients with IgA Nephropathy: The Secondary Phenomenon?

Ots¹,

Uibo²,

Metsküla

et al. 1999

Am J Nephrol

View full text Add to dashboard Cite

show abstract

“…Experimental models have increased the understanding of IgAN. Formation of IgA immune complexes, aberration of mucosal immune response, dietary antigens, viral infections, and polymeric IgA have been implicated in the development of IgAN [1]. Recent studies have provided compelling data that growth factors such as platelet-derived growth factor [2], cytokines such as interleukins, tumor necrosis factor, or interferon [3, 4], protooncogenes such as Fas and Bcl-2 [5], and eicosanoids such as thromboxane B 2 [6]are involved in the development of IgAN.…”

Section: Introductionmentioning

confidence: 99%

VCAM-1, ICAM-1, and E-Selectin in IgA Nephropathy and Schönlein-Henoch Syndrome: Differences between Tissue Expression and Serum Concentration

Mrowka

Heintz²,

Sieberth³

1999

Nephron

View full text Add to dashboard Cite

The tissue expressions of vascular cell adhesion molecule 1 (VCAM-1), intercellular adhesion molecule 1 (ICAM-1) and endothelial leukocyte adhesion molecule 1 (E-selectin-1) were investigated in biopsy specimens from 28 patients with different stages of IgA nephropathy (IgAN) and 20 patients with acute renal failure (ARF) or chronic renal diseases (amyloidosis, Alport’s glomerulopathy) by immunohistochemistry. The results were compared with the serum levels of the three adhesion molecules. VCAM-1 expression was significantly increased on parietal/tubular epithelial cells in IgAN and ARF. Significantly elevated circulating VCAM-1 levels were measured in IgAN and amyloidosis, but did not correlate with renal function (creatinine clearance). Significantly increased glomerular endothelial/epithelial ICAM-1 expression was found in IgAN and ARF. Intense mesangial ICAM-1 expression was found in mild stages of IgAN and in Schönlein-Henoch syndrome. Circulating ICAM-1 was not significantly elevated in IgAN and different renal diseases. VCAM-1 and ICAM-1 expressions of interstitial infiltrating cells were significantly higher in severe than in mild IgAN and associated with an increased infiltration of inflammatory leukocytes. Patients with IgAN and different renal diseases had decreased mesangial and almost absent interstitial E-selectin expression as compared with controls. The circulating E-selectin levels were significantly elevated in ARF. In conclusion, the tissue expression of adhesion molecules in IgAN reflects a continuous inflammatory renal activity. However, only increased circulating VCAM-1 serum levels correlated significantly with the histological state of renal inflammation and could be used as a disease marker.

show abstract

“…The amelioration of glomerular injury by α-tocopherol supplementation has also been observed in chronic puromycin aminonucleoside nephropathy, a severe glomerulonephropathy [7]. The recent demonstration that diabetes-induced accelerated apoptosis is related to free radical injury of the rat kidney [8] supports the use of αtocopherol in this most-common cause of end-stage renal disease.…”

Section: Discussionmentioning

confidence: 84%

“…The model of IgA nephropathy used in the experiments described in this paper takes advantage of protracted mucosal immunization to induce mesangial abnormalities and establish for the first time that the disease is already present at 4 weeks. The time frame of 4-8 weeks of BGG immunization, in which IgA nephropathy is demonstrated, appears to us to be relevant in designing an appropriate model [7,8] to study the molecular biology of renal injury by chronic vaccination and the factors involved with healing brought about by treatment. Finally, to our knowledge, this is the first experiment to describe spontaneous resolution of IgA mesangial immune deposition by 16 weeks using this disease model.…”

Section: Discussionmentioning

confidence: 99%

Influence of α-tocopherol over the time course of experimental IgA nephropathy

Kuemmerle

Krieg

Chan

et al. 1999

Pediatric Nephrology

View full text Add to dashboard Cite

The present study investigated the pathogenesis and the time course of kidney injury in experimental IgA nephropathy. In order to determine an appropriate period in the course of experimental IgA nephropathy to study renal injury and repair, we examined proteinuria and IgA deposition in the renal mesangium after 4, 8, and 16 weeks of mucosal challenge by bovine gamma globulins (BGG) provided in the drinking water. The hallmark of IgA deposition in the mesangium was present after 4 weeks and 8 weeks of BGG inoculation, but by 16 weeks, the mesangial IgA deposition had resolved. In addition, we confirmed our previous report on the beneficial effects of alpha-tocopherol in reducing proteinuria in IgA nephropathy at 8 weeks, and extended this observation to investigate the effects of dietary supplementation of alpha-tocopherol at both 4 weeks and 16 weeks. Proteinuria resolved spontaneously at 16 weeks. There is oxidative stress, as suggested by the elevation in plasma and renal malondialdehyde content, and increased fibrogenic cytokine message, as suggested by elevated transforming growth factor beta1 mRNA. These increases were clearly blunted by alpha-tocopherol at both 4 weeks and 8 weeks. Treatment with alpha-tocopherol was associated with a significant reduction in the severity of proteinuria. Thus, our data suggest that the period between 4 and 8 weeks of BGG vaccination could be relevant in designing an appropriate model to study the molecular biology of the pathogenesis of renal injury and the effects of treatment. The 16-week model may be useful in exploring gene expression involved with spontaneous resolution.

show abstract

Primary IgA Nephropathy: The Relevance of Experimental Models in the Understanding of Human Disease

Cited by 10 publications

References 41 publications

IgA-Antigliadin Antibodies in Patients with IgA Nephropathy: The Secondary Phenomenon?

IgA-Antigliadin Antibodies in Patients with IgA Nephropathy: The Secondary Phenomenon?

VCAM-1, ICAM-1, and E-Selectin in IgA Nephropathy and Schönlein-Henoch Syndrome: Differences between Tissue Expression and Serum Concentration

Influence of α-tocopherol over the time course of experimental IgA nephropathy

Contact Info

Product

Resources

About