Background/Purpose: Lupus nephritis (LN) is a severe manifestation of systemic lupus erythematosus (SLE) that leads to significant morbidity and mortality. Therefore, it is essential to identify biomarkers that predict incident LN in a newly diagnosed SLE patient. Anti-double stranded DNA antibodies (dsDNA) serve as a standard of care disease activity marker in patients with LN. However, the evidence for a predictive role of anti-dsDNA for incident LN is limited. To fill these knowledge gaps, we performed a case-control study to look at the association of anti-dsDNA in newly diagnosed SLE for future incident LN. We determined that the presence of and high titers of anti-dsDNA in newly diagnosed SLE are a significant predictor of future incident LN. Additionally, we found that the presence as well as the titers of anti-dsDNA at the time of SLE diagnosis predict earlier onset of LN. These results provide a roadmap for the use of anti-dsDNA levels to risk stratify newly diagnosed SLE patients. This stratification could guide disease activity monitoring to diagnose LN at an earlier stage.

Methods: In a prospective, observational case-control study, patients with the diagnosis of SLE were divided into cases (SLE patients with a biopsy proven LN) and controls (without LN). A logistic regression model was utilized to identify the predictive value of the presence of and high titers of anti-dsDNA for future incident LN. A survival analysis was performed to identify the time to new development of LN in relation to the presence of and high titers of anti-dsDNA.

Results: Of 394 SLE patients included in this study, 300 had LN, and 94 did not have LN. In univariate logistic regression analysis, the presence of and high titers of anti-dsDNA were associated with a significantly higher risk for incident LN. In a multivariate logistic regression model, the risk of incident LN was 2-fold with the presence of anti-dsDNA antibodies at the time of SLE diagnosis, adjusting for age, gender and sex (OR 2.1, CI 1.2- 3.4, p 0.005). In comparison to Caucasians the African Americans had a 5-fold risk of developing LN. In a multivariate Cox proportional hazard model, the adjusted risk for the early development of LN was 44% higher in those with anti-dsDNA. The adjusted risk was about 5-fold for other races in comparison to Caucasian race. By utilizing titers as a continuous variable in the multivariate model, the adjusted risk for early development of LN increased by 8.3% for each doubling of anti-dsDNA. In Kaplan Meier analysis, the median time(month) to development of LN among patients who had a positive anti-dsDNA with new onset SLE was much shorter than patients who did not have anti-dsDNA with new onset SLE (14.4 vs 34.4, p 0.003).Similarly, the median time to incident LN among patients with high anti-dsDNA titers (≥2 times the upper limit of normal) was significantly lower compared to those with lower anti-dsDNA titers (12.3 vs 39.0,p < 0.001).

Conclusion: Younger age, African American race, presence of anti-dsDNA and high titers of anti-dsDNA at the time of SLE diagnosis are significant predictors for the incident LN.

Younger age, Hispanic ethnicity, non-Caucasian race, and presence of anti-dsDNA antibody at the time of SLE diagnosis increased the likelihood of a more rapid progression to LN.

Baseline characteristics of SLE patients with and without lupus nephritis

Cox proportional analysis for incident LN by dsDNA titers

Kaplan-Meier survival curve for the incident lupus nephritis based on the titers of anti-dsDNA at the time of SLE diagnosis

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/the-role-of-anti-dsdna-antibodies-in-predicting-incident-lupus-nephritis-in-newly-diagnosed-lupus/