Double positivity for anti-dsDNA and anti-Sm antibodies represents higher disease activity in systemic lupus erythematosus.

Background: Several studies have shown that anti-dsDNA and anti-Sm antibodies not only contribute to the classification of systemic lupus erythematosus (SLE) but also strongly correlate with disease activity. However, the relationship between double positivity for anti-dsDNA and anti-Sm antibodies and disease activity remains unclear.

Objectives: This study aimed to assess the clinical significance of double positivity for anti-dsDNA and anti-Sm antibodies in SLE.

Design: A single-center retrospective study was conducted, consecutively enrolled hospitalized patients with SLE who underwent anti-dsDNA and anti-Sm antibody testing between June 2009 and December 2022.

Methods: In this study, clinical data were collected from the electronic medical records of all study participants. SLE Disease Activity Index 2000 (SLEDAI 2000) scores were calculated; SLEDAI 2000 scores excluding anti-dsDNA scores were defined as modified SLEDAI 2000 (mSLEDAI 2000) scores. Severe disease activity was defined as a SLEDAI 2000 score of >12.

Results: The study included 408 patients with SLE; of them, 95 were double-positive for anti-dsDNA and anti-Sm antibodies, 193 were single-positive for anti-dsDNA or anti-Sm antibodies, and 120 were double-negative. The double-positive group showed more clinical manifestations, lower C3 and C4 levels, and higher SLEDAI 2000 and mSLEDAI 2000 scores compared to the double-negative and single-positive groups. During follow-up, double-positive patients, whether converted to single-positive or double-negative, showed a significant decrease in SLEDAI 2000 and mSLEDAI 2000 scores, but the improvement in SLEDAI 2000 scores was not significant in patients with persistent double positivity. In recognizing severe disease activity, double positivity had the highest specificity, positive predictive value, positive likelihood ratio, and highest Youden index, albeit with the lowest sensitivity, compared to anti-dsDNA positivity, anti-Sm positivity, and positivity for anti-dsDNA and/or anti-Sm antibodies. Furthermore, a higher proportion of patients with double positivity were treated with high-dose or shock-dose glucocorticoids.

Conclusion: Double positivity for anti-dsDNA and anti-Sm antibodies suggests higher disease activity in patients with SLE who may require more intense immunosuppressive therapy.