Glomerulonephritis induced in the rabbit by antiendothelial antibodies.

Matsuo, Seiichi; Fukatsu, Atsushi; Taub, Mary; Caldwell, P. R. B.; Brentjens, Jan R.; Andres, Giuseppe A.

doi:10.1172/jci113021

Cited by 73 publications

(29 citation statements)

References 52 publications

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“…In addition, Matsuo et al (1987) injected rabbits with labelled antibodies directed against endothelial membranebound angiotensin-converting enzyme. The labelled antibodies were detected on the surface of glomerular endothelial cells and a mild, transient but consistently reproducible nephrotoxic glomerulonephritis developed which was documented histologically.…”

Section: Discussionmentioning

confidence: 99%

“…AECA have also been described in IgA nephropathy (Yap et al, 1988) and in addition, interest has been directed at the presence of AECA in acute and chronic renal transplant rejection where endothelial damage occurs at an early stage in the rejected organ (Cerilli et al, 1977;Paul, Claas & van Es, 1979;Claas et al, 1980). It has been further suggested that AECA may have a role in the development of glomerulonephritis (Matsuo et al, 1987).…”

Section: Introductionmentioning

confidence: 99%

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Antibodies to endothelial cells in systemic lupus erythematosus: a potential marker for nephritis and vasculitis

D’Cruz

Houssiau

Ramírez

et al. 1991

Clinical and Experimental Immunology

112

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SUMMARYUsing an ELISA, anti-endothelial cell antibodies (AECA) have been found in sera obtained at the time of renal biopsy in 46 out of 57 patients (81%) with systemic lupus erythematosus (SLE) and nephritis (mean binding index (BI) = 84% ± 52 8) compared with 22 out of 50 SLE patients (44%) without nephritis (mean BI = 45% ±35-9). Seventy normal human sera had a mean BI of 10% ±9 8. The highest levels were seen in patients with diffuse proliferative glomerulonephritis (WHO grade IV) and in patients with proteinuria and nephrotic syndrome. When the biopsies were assessed for activity and chronicity scores, AECA were associated with active renal lesions (/'<0 001). AECA levels correlated with low complement levels but not with anti-DNA antibodies to extractable nuclear antigens (ENA), anti-cardiolipin or anti-neutrophil cytoplasmic antibodies. The presence of AECA conferred a positive predictive value of 0-68 for the presence of nephritis. Twenty-five patients had active vasculitis at the time of assay and the highest AECA values were seen in patients with both nephritis and vasculitis. No correlation was seen with serum immunoglobulin levels and immune complexes did not bind significantly to the endothelial surface. The possible role ofthese antibodies as a marker in lupus nephritis is discussed.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Antibodies to endothelial cells in systemic lupus erythematosus: a potential marker for nephritis and vasculitis

D’Cruz

Houssiau

Ramírez

et al. 1991

Clinical and Experimental Immunology

112

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“…DPPIV-anti-DPPIV immune complexes formed at the surface of glomerular endothelial cells may be shed in the capillary lumen, partly dissociate, then be filtered through the glomerular capillary wall, and finally reassociate on the outer aspect of the glomerular basement membrane. This pathophysiologic scenario occurs in a model of MN induced in the rabbit by polyclonal antibodies to angiotensin-converting enzyme, which is expressed by glomerular endothelial cells but not by rabbit's podocytes (24).…”

Section: From Bench To Bedside: Hn and Other Experimental Models Of Mnmentioning

confidence: 99%

Molecular Pathomechanisms of Membranous Nephropathy

Ronco

Dębiec²

2005

Journal of the American Society of Nephrology

123

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Membranous nephropathy (MN), the most common cause of idiopathic nephrotic syndrome in white adults, is characterized by an accumulation of immune deposits on the outer aspect of the glomerular basement membrane. In Heymann nephritis, the rat experimental model for MN, megalin-the target antigen of the nephritogenic antibodies-is expressed on the surface of podocytes, where immune complexes are formed, leading to complement activation and nephrotic-range proteinuria. However, megalin cannot be held responsible for human MN because it has not been found in human podocytes or detected in subepithelial immune deposits in patients with MN. Several potential antigens have been identified in so-called secondary forms of MN, but there is no real proof that these antigens are pathogenic. In a subgroup of infants with antenatal MN, neutral endopeptidase (NEP) has been identified as the first protein target on human podocytes of nephritogenic antibodies. The infants' mothers became immunized during pregnancy against NEP expressed on syncytiotrophoblastic cells because they were NEP deficient as a result of truncating mutations in the MME gene. Severity of neonatal renal disease was determined by the mothers' IgG response that led to the formation of the membrane attack complex of complement in the subepithelial deposits. Alloimmunization against NEP is a novel pathomechanism of MN that might also account for some cases of MN after renal or bone marrow transplantation. Other types of alloimmunization should be investigated in MN but also in other renal and nonrenal diseases, particularly those that affect the pediatric age.

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“…28,29 Indeed, transfer of AECA into rabbits results in systemic lupus erythematosus-like nephritis. 30 It is likely that such antibodies act in concert with other immunological factors to exacerbate vascular damage. 20,24 A humoral immunological contribution to atherosclerosis is also recognized.…”

Section: Introductionmentioning

confidence: 99%

Evidence for a novel human-specific xeno-auto-antibody response against vascular endothelium

Pham¹,

Gregg²,

Karp³

et al. 2009

Blood

109

137

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Humans are genetically unable to synthesize the common mammalian sialic acid N-glycolylneuraminic acid (Neu5Gc). However, Neu5Gc can be metabolically incorporated and covalently expressed on cultured human cell surfaces. Meanwhile, humans express varying and sometimes high titers of polyclonal anti-Neu5Gc antibodies. Here, a survey of human tissues by immunohistochemistry with both a monospecific chicken anti-Neu5Gc antibody and with affinity-purified human antiNeu5Gc antibodies demonstrates endothelial expression of Neu5Gc, likely originating from Neu5Gc-rich foods like red meats. We hypothesized that the combination of Neu5Gc incorporation and anti-Neu5Gc antibodies can induce endothelial activation. Indeed, the incubation of high-titer human sera with Neu5Gc-fed endothelial cells led to Neu5Gc-dependent antibody binding, complement deposition, endothelial activation, selectin expression, increased cytokine secretion, and monocyte binding. The proinflammatory cytokine tumor necrosis factor-␣ also selectively enhanced human anti-Neu5Gc antibody reactivity. AntiNeu5Gc antibodies affinity-purified from human serum also directed Neu5Gc-dependent complement deposition onto cultured endothelial cells. These data indicate a novel human-specific mechanism in which Neu5Gc-rich foods deliver immunogenic Neu5Gc to the endothelium, giving anti-Neu5Gc antibody-and complement-dependent activation, and potentially contributing to human vascular pathologies. In the case of atherosclerosis, Neu5Gc is present both in endothelium overlying plaques and in subendothelial regions, providing multiple pathways for accelerating inflammation in this disease.

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Glomerulonephritis induced in the rabbit by antiendothelial antibodies.

Cited by 73 publications

References 52 publications

Antibodies to endothelial cells in systemic lupus erythematosus: a potential marker for nephritis and vasculitis

Antibodies to endothelial cells in systemic lupus erythematosus: a potential marker for nephritis and vasculitis

Molecular Pathomechanisms of Membranous Nephropathy

Evidence for a novel human-specific xeno-auto-antibody response against vascular endothelium

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