Anti-dsDNA antibodies and disease classification in antinuclear antibody positive patients: the role of analytical diversity

Haugbro, Kaia

doi:10.1136/ard.2003.016303

Cited by 99 publications

(104 citation statements)

References 51 publications

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“…Among 81 randomly selected ANA-positive individuals, 19 fulfilled the ACR criteria for SLE, while the remaining 62 non-SLE patients had other autoimmune or nonautoimmune disorders (22). Four SLE patients (21%) were positive for anti-␣-actinin antibodies (Figure 1C), while 3 of these patients (16%) were doublepositive for ␣-actinin and dsDNA (data not shown).…”

Section: Resultsmentioning

confidence: 96%

“…As a control, 81 consecutively collected antinuclear antibody (ANA)-positive sera were studied. Diagnoses were established independent of assay results, as previously described (22). The study was approved by the regional ethics board.…”

Section: Methodsmentioning

confidence: 99%

“…All mAb, serum antibodies, and antibodies eluted from kidneys were diluted 2-fold in PBS-0.02% Tween 20. Relevant control antibodies were included in each ELISA for intraassay validation of results (22,29). The Crithidia luciliae immunofluorescence test (CLIFT) was performed to detect anti-dsDNA antibodies, as previously described (31).…”

Section: Methodsmentioning

confidence: 99%

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Critical comparative analyses of anti–α‐actinin and glomerulus‐bound antibodies in human and murine lupus nephritis

Kalaaji¹,

Sturfelt²,

Mjelle³

et al. 2006

Arthritis & Rheumatism

102

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Objective. Although anti-double-stranded DNA (anti-dsDNA) antibodies are important in lupus nephritis, the question regarding which glomerular structures (␣-actinin, nucleosomes, or others) are recognized by nephritogenic anti-dsDNA antibodies is still controversial. In this study, we determined which glomerular structures are recognized by monoclonal and in vivobound nephritogenic antibodies.Methods.Western blotting was used to analyze the ability of nephritogenic anti-dsDNA antibodies to recognize glomerular and nucleosomal structures. Sera from patients with lupus nephritis, sera from random antinuclear antibody-positive patients, and paired antibodies from sera and kidney eluates from nephritic (NZB ؋ NZW)F 1 mice were analyzed for activity against proteins identified by monoclonal nephritogenic antibodies, and against ␣-actinin, dsDNA, nucleosomes, histone H1, heparan sulfate, DNase I, and type IV collagen. Immunoelectron microscopy was used to determine the glomerular localization of ␣-actinin and in vivo-bound autoantibodies in nephritic (NZB ؋ NZW)F 1 mouse kidneys.Results. Anti-␣-actinin antibodies were observed in human and murine lupus nephritis sera and in sera from patients without systemic lupus erythematosus and were not detected in kidney eluates from nephritic mice. Antibodies to dsDNA and histone H1 were detected in all eluates. Western blot analyses revealed that nephritogenic anti-dsDNA antibodies recognized a 32-kd band, identified as histone H1. Competitive enzyme-linked immunosorbent assay demonstrated that nephritogenic monoclonal antibodies, and dominant antibodies eluted from nephritic kidneys, cross-reacted with dsDNA and H1. This cross-reactive anti-H1 specificity was largely absent in sera from those mice. Immunoelectron microscopic analysis of nephritic (NZB ؋ NZW)F 1 mouse kidneys revealed that antibodies eluted from kidneys, but not anti-␣-actinin antibodies, bound to distinct nephritis-associated electrondense structures linked to glomerular basement membranes. Conclusion.Cross-reactive anti-dsDNA/antihistone H1 antibodies, but not anti-␣-actinin antibodies, are central among those deposited in nephritic glomeruli.

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Section: Resultsmentioning

confidence: 96%

Section: Methodsmentioning

confidence: 99%

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Critical comparative analyses of anti–α‐actinin and glomerulus‐bound antibodies in human and murine lupus nephritis

Kalaaji¹,

Sturfelt²,

Mjelle³

et al. 2006

Arthritis & Rheumatism

102

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“…Most studies link lupus nephritis to the presence of nephritogenic high avidity anti-dsDNA Ab as detected by C. luciliae immunofluorescence or the Farr radioactivity assay [28][29][30] . Anti-dsDNA Ab are, however, often present long before SLE is clinically apparent and they gradually obtain their nephritogenic potential through repeated antigenic stimulation 28,31,32 . Several short-term prospective studies have shown that intensive anti-dsDNA Ab surveillance can help prevent disease flares such as lupus nephritis 33,34 .…”

Section: Discussionmentioning

confidence: 99%

The Influence of the 1997 Updated Classification Criteria for Systemic Lupus Erythematosus: Epidemiology, Disease Presentation, and Patient Management

Eilertsen¹,

Becker-Merok²,

Nossent³

2009

J Rheumatol

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ABSTRACT. Objective. The 1997 update of the American College of Rheumatology classification criteria (ACR97) for systemic lupus erythematosus (SLE) has not been validated. We determined to what extent their introduction influenced the epidemiology and clinical characteristics of the disease in northern Norway. Methods. Annual incidence and point-prevalence rates, clinical manifestations, and outcome were determined in an inception cohort of patients with SLE in northern Norway, included between 1996 and 2006, using ACR97 criteria (97acr). These findings were compared with a cohort from the same area enrolled 1978-1995 using the 1982 revised criteria ACR82 (82acr). Results. The mean annual incidence of SLE was 3.00 for cohort 97acr (n = 58) versus 2.63 for cohort 82acr (n = 81) (p = 0.5). All patients in the 97acr cohort also fulfilled the 1982 criteria; however, significantly fewer patients presented with discoid rash [odds ratio (OR) 0.31)], arthritis (OR 0.24), renal (OR 0.28) or hematological disorder (OR 0.27), and significantly more with anti-dsDNA (OR 2.57) and antiphospholipid antibodies (OR 27.9). Initial treatment with intravenous pulse methylprednisolone (OR 9.23), azathioprine (OR 6.32), and low-dose aspirin (OR 20.9) was increased in cohort 97acr. Five-(95.2%) and 10-year survival (91.9%) rates were also improved for cohort 97acr. Conclusion. The ACR97 criteria set has construct validity compared to the ACR82 criteria set. SLE incidence remains unchanged in northern Norway, but a significant reduction of renal disease and further improvements in survival rates occurred simultaneously with increased serological surveillance with ELISA-based assays and early immunosuppressive and anticoagulant therapy.

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“…Affinity-maturated IgG antibodies to doublestranded DNA (dsDNA) and nucleosomes are strongly associated with systemic lupus erythematosus (SLE) (1,2) and are included in the American College of Rheumatology classification criteria for the disease (3). Although we have gained insight into requirements for the experimental induction of antibodies to dsDNA (4)(5)(6), the molecular and cellular bases for their generation in SLE are still poorly understood (6)(7)(8).…”

mentioning

confidence: 99%

Reduced fragmentation of apoptotic chromatin is associated with nephritis in lupus‐prone (NZB × NZW)F₁ mice

Zykova¹,

Seredkina²,

Benjaminsen³

et al. 2008

Arthritis & Rheumatism

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Objective. Antinucleosome autoantibodies are pathogenic factors in lupus nephritis. Defects in apoptotic pathways may result in increased levels of apoptotic nucleosomes. The objectives of this study were 1) to determine whether low molecular weight oligonucleosomes are present in the kidneys of autoimmune (NZB ؋ NZW)F 1 mice, 2) to analyze whether the presence of glomerular membrane-associated TUNELpositive electron-dense structures reflect the existence of low molecular weight oligonucleosomes, and 3) to determine an eventual temporal relationship between glomerular electron-dense structures, oligonucleosomes, and proteinuria in these mice.Methods. DNA was isolated from mouse 111s34 hybridoma cells and from the kidneys of normal BALB/c mice in which apoptosis was induced by camptothecin and from the kidneys of (NZB ؋ NZW)F 1 mice at ages 4 weeks, 8 weeks, 20 weeks, and >26 weeks (nephritic mice). The DNA fragmentation pattern was determined with an Agilent bioanalyzer. An electron microscopybased TUNEL assay was performed to detect apoptotic chromatin in glomerular membranes, and immunoelectron microscopy was used to determine antibody binding. Transcription levels for nucleases associated with apoptosis and necrosis were determined by real-time polymerase chain reaction.Results. DNA from camptothecin-treated cell lines and BALB/c mouse kidneys, but not that from untreated (NZB ؋ NZW)F 1 mouse kidneys, demonstrated DNA cleavage consistent with apoptotic fragmentation. DNA from (NZB ؋ NZW)F 1 mice was devoid of apoptotic fragmentation, irrespective of the age of the mice, whereas TUNEL-positive chromatin particles were detected in glomerular membranes in nephritic mice. Renal DNase I transcription was reduced in nephritic mice. Nucleosomal DNA fragmentation in response to camptothecin exposure was highly reduced in (NZB ؋ NZW)F 1 mouse kidneys compared with that in their normal counterparts.Conclusion. The results of this study demonstrate that TUNEL-positive chromatin particles are deposited in the glomeruli of nephritic (NZB ؋ NZW)F 1 mice, due to reduced fragmentation and clearance of chromatin.

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Anti-dsDNA antibodies and disease classification in antinuclear antibody positive patients: the role of analytical diversity

Cited by 99 publications

References 51 publications

Critical comparative analyses of anti–α‐actinin and glomerulus‐bound antibodies in human and murine lupus nephritis

Critical comparative analyses of anti–α‐actinin and glomerulus‐bound antibodies in human and murine lupus nephritis

The Influence of the 1997 Updated Classification Criteria for Systemic Lupus Erythematosus: Epidemiology, Disease Presentation, and Patient Management

Reduced fragmentation of apoptotic chromatin is associated with nephritis in lupus‐prone (NZB × NZW)F₁ mice

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Anti-dsDNA antibodies and disease classification in antinuclear antibody positive patients: the role of analytical diversity

Cited by 99 publications

References 51 publications

Critical comparative analyses of anti–α‐actinin and glomerulus‐bound antibodies in human and murine lupus nephritis

Critical comparative analyses of anti–α‐actinin and glomerulus‐bound antibodies in human and murine lupus nephritis

The Influence of the 1997 Updated Classification Criteria for Systemic Lupus Erythematosus: Epidemiology, Disease Presentation, and Patient Management

Reduced fragmentation of apoptotic chromatin is associated with nephritis in lupus‐prone (NZB × NZW)F1 mice

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Reduced fragmentation of apoptotic chromatin is associated with nephritis in lupus‐prone (NZB × NZW)F₁ mice