Increased Intestinal Permeability to (51 Cr) EDTA Is Correlated with IgA Immune Complex‐Plasma Levels in Children with IgA‐Associated Nephropathies

Abstract

Intestinal permeability was investigated in 10 normal young adults, in 11 control children and in 9 children presenting with either Berger disease (4 cases) or Henoch-Schönlein nephritis (5 cases), making use of (51 Cr) EDTA as a probe molecule. All subjects exhibited a normal creatinine clearance at the time of testing. After oral administration of (51 Cr) EDTA, 24-hour urine radioactivity was measured and results were expressed in percentage of the oral dose administered. Means and SD were 2.35% +/- 0.77, 2.51% +/- 0.70, and 5.10% +/- 2.35 for normal adults, control children and patients with IgA-associated nephropathies, respectively. The differences of permeability between controls and patients were statistically significant (p less than 0.01). In addition, a significant, direct, linear correlation has been established between the percentage of (51 Cr) EDTA excreted in 24-hour urine and IgA immune complex-plasma levels. Our results therefore support the hypothesis that increased gut permeability could play a role in the pathogenesis of IgA-associated nephropathies.

Henoch-Schönlein Purpura Nephritis

“…N-Acetylgalactosamine (GalNac) residues exposed on IgA1 because of the lack of terminal ␤1 galactosylation constitute a novel antigen inducing a humoral auto-immune response (29). The possible impaired resistance to antigen penetration at mucosal levels suggested in HSPN by an increased intestinal permeability (30) and in IgAN by a reduced mucosal immune reaction to novel antigen (31) might contribute to the production of large amounts of GalNac-IgA1 that cannot be cleared by the asialoglycoprotein receptor of hepatocytes binding specifically to ␤1,3-galactosyl-IgA1. Accumulating GalNaC-IgA1 in polymeric forms (pIgA) in circulating blood favors the formation of large IgA1-CC that deposit in different tissues and induce local inflammation.…”

The Role of Intestinal Barrier Function in Early Life in the Development of Colitis

“…There is increasing evidence to suggest intestinal barrier dysfunction results in immune responses that can target any organ or tissue in genetically predisposed individuals (Fasano & Shea-Donohue, 2005;Fasano, 2011), such as the skeletal system (ankylosing spondylitis, rheumatoid arthritis: Edwards, 2008), pancreas (type 1 diabetes: (Carratù et al, 1999), kidney (IgA nephropathy: Davin et al, 1988), liver (nonalcoholic steatohepatitis: Wigg et al, 2001), and brain (multiple sclerosis; Yacyshyn et al, 1996). Barrier dysfunction can also result in an aberrant or exaggerated inflammatory response to the intestinal microbiota.…”

Do Intestinal Hyperpermeability and the Related Food Antigens Play a Role in the Progression of IgA Nephropathy?

“…Typical of its his tology is the predominance of IgA granular deposits in the glomeruli, primarily in the mesangium [2][3][4], The patho genesis of the disease is unknown, but an immune com plex etiology is most likely [3][4][5][6]; however, nonhomogenous immunopathogenicity has also been suggested [5,6]. Several authors have studied the role of viral and bacterial infections [7][8][9], bone marrow Ig synthesis [10], the im mune system (complement [11,12], cytokines [13], IgA disregulation [6,14]), mucosal immune protective capaci ty [ 15,16], and increased absorption of food antigens [ 17,18] in the development of the disease. In both children [ 15] and adults [ 19] with IgA NP.…”

“…Several authors have studied the role of viral and bacterial infections [7][8][9], bone marrow Ig synthesis [10], the im mune system (complement [11,12], cytokines [13], IgA disregulation [6,14]), mucosal immune protective capaci ty [ 15,16], and increased absorption of food antigens [ 17,18] in the development of the disease. In both children [ 15] and adults [ 19] with IgA NP. increased intestinal per meability, which may cause chronic antigen entry with constant antibody production, has been demonstrated.…”