Tubulo‐interstitial disease in lupus nephritis. A morphometric study

Magil, Alex B.; Tyler, M.

doi:10.1111/j.1365-2559.1984.tb02324.x

Cited by 29 publications

(9 citation statements)

References 17 publications

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“…While predominantly tubular deposition is not common in human lupus nephritis (32), immune deposits may be present in tubular basement membranes and interstitium in 50% of kidney biopsies from patients with SLE (33,34). In a study by Park et al (35), the prevalence of tubular immune deposits correlated with activity and severity of glomerular lesions, as well as with the degree of renal insufficiency.…”

Section: Discussionmentioning

confidence: 99%

The double edged sword of the immune response: mutational analysis of a murine anti-pneumococcal, anti-DNA antibody.

Putterman¹,

Limpanasithikul²,

Edelman³

et al. 1996

J. Clin. Invest.

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Anti-double-stranded (ds) DNA antibodies are not only an important diagnostic marker for SLE, but also play an important role in tissue injury. Microbial antigen may be a stimulus for the production of these antibodies. We isolated 99D.7E, an IgG2b monoclonal antibody from a nonautoimmune BALB/c mouse that is cross-reactive with both ds-DNA and phosphorylcholine, the dominant hapten on the pneumococcal cell wall. While partially protective against a bacterial challenge, 99D.7E is also pathogenic to the kidney. To identify those molecular motifs that confer on anti-PC antibodies the potential for autoreactivity, we created a panel of 99D.7E mutants with single amino acid substitutions in the heavy chain, and examined the changes in antigen binding and renal deposition. Our results support the hypothesis that charge and affinity for dsDNA are not adequate predictors of the pathogenicity of anti-DNA antibodies. Differential renal damage from anti-dsDNA antibodies may be due to differences in fine specificity, rather than differential affinity for dsDNA. Importantly, high affinity IgG antibodies cross-reactive with bacterial and self antigen exist and can display pathogenic potential, suggesting that defects in peripheral regulation of B cells, activated by foreign antigen but cross-reactive with self antigen, might lead to autoimmune disorders. ( J. Clin. Invest. 1996. 97:2251-2259.)

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Section: Discussionmentioning

confidence: 99%

The double edged sword of the immune response: mutational analysis of a murine anti-pneumococcal, anti-DNA antibody.

Putterman¹,

Limpanasithikul²,

Edelman³

et al. 1996

J. Clin. Invest.

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“…In lupus nephritis, tubulointerstitial immune deposits (TID) almost invariably found in glomeruli are also fre quently present in or along the tubular basement mem branes (TBM), in the wall of small arteries and of intersti tial capillaries, and in the interstitium proper [1][2][3][4][5][6][7]. Ex traglomerular deposits are more likely to be found when glomerular disease is both severe and active and are commonly associated with varying degrees of interstitial inflammation (II).…”

Section: Introductionmentioning

confidence: 99%

Tubulointerstitial Disease in Lupus Nephritis: Relationship to Immune Deposits, Interstitial Inflammation, Glomerular Changes, Renal Function, and Prognosis

Park¹,

D’Agati²,

Appel

et al. 1986

Nephron

126

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The interrelationships between tubulointerstitial immune deposits (TID), interstitial inflammation, glomerular changes, renal function, and prognosis were assessed in the renal biopsies from 93 patients with lupus nephritis. The prevalence of TID was 33% by immunofluorescence and 23% by electron microscopy. Although predominantly detected along and within tubular basement membranes, extraglomerular immune deposits were also present in the wall of renal interstitial capillaries and small arteries as well as in Bowman’s capsule. The prevalence of TID correlated with the activity of glomerular lesions and, to a lesser extent, with the severity of proliferative lupus nephritis (WHO classes II-IV).TID were much less common in the membranous form (WHO class V). The severity of interstitial inflammation correlated with the degree of renal insufficiency and was an accurate prognostic indicator of progressive deterioration of renal function. However, there was no correlation between prevalence of TID and prevalence and severity of interstitial inflammation, suggesting that the latter is not necessarily secondary to the presence of immune complexes and that other pathogenetic mechanisms may be involved.

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“…Anti-DNA antibodies (Ab) are implicated in the pathogenesis of LN. Their levels correlate with disease activity, and they deposit in the glomerulus and along the tubular basement membrane (1)(2)(3)(4). Immune deposition is associated with induction of inflammatory cytokines such as IL-6 (5).…”

mentioning

confidence: 99%

“…Proximal tubular epithelial cells (PTEC) are polarized cells that constitute the predominant cell type within the tubulointerstitium. Although previously considered to be involved mainly in transport of fluid and electrolytes, there is increasing evidence to demonstrate the critical role of PTEC in the immunopathogenesis of various renal parenchymal diseases (23,24), in particular to act as a directional regulator/effector of immune-mediated inflammation and fibrosis (3,23).…”

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confidence: 99%

Effect of Human Anti-DNA Antibodies on Proximal Renal Tubular Epithelial Cell Cytokine Expression

Yung

Tsang²,

Sun³

et al. 2005

Journal of the American Society of Nephrology

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This study aimed to investigate the effects of human anti-DNA antibodies (Ab) from patients with lupus on renal proximal tubular epithelial cells (PTEC), focusing on alterations in cell morphology and proinflammatory cytokine synthesis. Immunohistochemistry showed increased tubulointerstitial IL-6 expression and IgG deposition in renal biopsies from patients with diffuse proliferative lupus nephritis, not observed in controls or membranous lupus nephritis, which correlated with the severity of inflammatory cell infiltration. Sera from patients with lupus nephritis contained IgG that bound to cultured PTEC. Such binding increased with disease activity and correlated with the level of anti-DNA Ab. Incubation of PTEC with anti-DNA Ab that were isolated during active (active Ab) or inactive (inactive Ab) disease induced IL-6 synthesis, both apically and from the basolateral aspect. This was accompanied by altered cell morphology, increased cell proliferation (P < 0.05), and lactate dehydrogenase release (P < 0.05). The binding of inactive Ab and active Ab to PTEC resulted in differential and sequential upregulation of TNF-␣, IL-1␤, and IL-6 secretion (P < 0.05). Early induction of TNF-␣ was observed with active Ab; the two then acted synergistically to induce IL-6 secretion. Exposure of PTEC to inactive Ab was associated with modest induction of TNF-␣, which was not involved in downstream induction of other proinflammatory peptides. These data suggest distinct immunopathogenetic mechanisms during disease flare or remission. Conditioned media from human mesangial cells acted synergistically with anti-DNA Ab to induce cytokine secretion in PTEC. Results from these studies underscore the pivotal role of PTEC in the pathogenesis of tubulointerstitial inflammation and fibrosis in lupus nephritis.

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Tubulo‐interstitial disease in lupus nephritis. A morphometric study

Cited by 29 publications

References 17 publications

The double edged sword of the immune response: mutational analysis of a murine anti-pneumococcal, anti-DNA antibody.

The double edged sword of the immune response: mutational analysis of a murine anti-pneumococcal, anti-DNA antibody.

Tubulointerstitial Disease in Lupus Nephritis: Relationship to Immune Deposits, Interstitial Inflammation, Glomerular Changes, Renal Function, and Prognosis

Effect of Human Anti-DNA Antibodies on Proximal Renal Tubular Epithelial Cell Cytokine Expression

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