Original Investigation
Pathogenesis and Treatment of Kidney Disease
Antinucleosome Antibodies as a Marker of Active Proliferative Lupus Nephritis

https://doi.org/10.1053/j.ajkd.2007.10.041Get rights and content

Background

Antinucleosome autoantibodies were previously described to be a marker of active lupus nephritis. However, the true prevalence of antinucleosome antibodies at the time of active proliferative lupus nephritis has not been well established. Therefore, the aim of this study is to define the prevalence and diagnostic value of autoantibodies against nucleosomes as a marker for active proliferative lupus nephritis.

Study Design

Prospective multicenter diagnostic test study.

Setting & Participants

35 adult patients with systemic lupus erythematosus (SLE) at the time of the renal biopsy showing active class III or IV lupus nephritis compared with 59 control patients with SLE.

Index Test

Levels of antinucleosome antibodies and anti–double-stranded DNA (anti-dsDNA) antibodies.

Reference Test

Kidney biopsy findings of class III or IV lupus nephritis at the time of sampling in a study population versus clinically inactive or no nephritis in a control population.

Results

Increased concentrations of antinucleosome antibodies were found in 31 of 35 patients (89%) with active proliferative lupus nephritis compared with 47 of 59 control patients (80%) with SLE. No significant difference between the 2 groups with regard to number of positive patients (P = 0.2) or antibody concentrations (P = 0.2) could be found. The area under the receiver operating characteristic curve as a marker of the accuracy of the test in discriminating between proliferative lupus nephritis and inactive/no nephritis in patients with SLE was 0.581 (95% confidence interval, 0.47 to 0.70; P = 0.2). Increased concentrations of anti-dsDNA antibodies were found in 33 of 35 patients (94.3%) with active proliferative lupus nephritis compared with 49 of 58 control patients (84.5%) with SLE (P = 0.2). In patients with proliferative lupus nephritis, significantly higher titers of anti-dsDNA antibodies were detected compared with control patients with SLE (P < 0.001). The area under the receiver operating characteristic curve in discriminating between proliferative lupus nephritis and inactive/no nephritis in patients with SLE was 0.710 (95% confidence interval, 0.60 to 0.82; P < 0.001).

Conclusions

Antinucleosome antibodies have a high prevalence in patients with severe lupus nephritis. However, our data suggest that determining antinucleosome antibodies is of limited help in the distinction of patients with active proliferative lupus nephritis from patients with SLE without active renal disease.

Section snippets

Participants

In this prospective multicenter study, all consecutive adult patients with SLE undergoing renal biopsy for suspected proliferative lupus nephritis were included.16 Patients had to fulfill at least 4 of the 11 American College of Rheumatology (ACR) criteria,17, 18 be at least 18 years old, and give written informed consent for study participation. All patients were recruited between August 1998 and October 2006 at the University Hospitals in Basel, Geneva, and Lausanne (Switzerland), Madrid

Participants and Test Results

Thirty-five of 40 patients with SLE undergoing renal biopsy had class III or IV lupus nephritis. Patient characteristics are listed in Table 1.

Antinucleosome antibodies were found in 31 of 35 patients (89%) with biopsy-proven active proliferative lupus nephritis. In the control populations, 19 of 23 patients with SLE (83%) with a history of lupus nephritis, but without clinical signs of activity at the time of sampling, and 28 of 36 patients with SLE (78%) without clinical signs of lupus

Discussion

The aim of this study is to determine the prevalence and diagnostic value of autoantibodies against nucleosomes in the diagnosis of proliferative lupus nephritis. Determination of antinucleosome antibodies at the time of the renal biopsy showing active proliferative lupus nephritis was considered to be the ideal tool to address the question because it should allow showing maximum differences in autoantibody concentrations compared with control patients with inactive SLE. In this setting, the

Acknowledgements

Support: Dr Trendelenburg is a recipient of a SCORE fellowship from the Swiss National Foundation (3232B0-107248/1 and 3200B0-107249/1) and was supported by a grant from the Novartis Foundation for Medical and Biological Research.

Financial Disclosure: None.

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Originally published online as doi:10.1053/j.ajkd.2007.10.041 on January 21, 2008.

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