Arthritis & rheumatology (Hoboken, N.J.), 12 2 2025 Differences in dynamics of specific anti-nuclear antibodies and their susceptibility to B cell targeting treatment in Systemic Lupus Erythematosus. van Dooren HJ, van Schaik M, Dorjée AL, Arends EJ, Mackay M, Laura C, Fox DA, Wofsy D, Smilek D, Aranow C, Dall'Era M, Huizinga TWJ, van Kooten C, Toes REM, Diamond B, Teng YKO, Suurmond J
Objective
The presence of anti-nuclear antibodies (ANAs) is characteristic for systemic lupus erythematosus (SLE). Antibody dynamics over time are thought to reflect the cellular source of ANAs and their therapeutic targetability. Anti-dsDNA is the most prevalent and well-studied of all ANAs, and fluctuations in anti-dsDNA serum levels are associated with disease activity. Antibody dynamics of other ANAs, such as antibodies targeting RNA-binding proteins (RBPs), are often considered more stable compared to anti-dsDNA. However, anti-RBPs may be heterogeneous in nature and their fluctuation has not been extensively analysed. Therefore, we aimed to study the dynamics of the different ANAs and their susceptibility to B cell targeting treatments in SLE patients.
Methods
Seroconversion of specific ANAs was analyzed using electronic health records from SLE patients. Titers of specific ANAs and anti-varicella zoster virus (VZV) were determined in serum from a longitudinal SLE patient cohort, and serum from SLE patients treated with rituximab and belimumab.
Results
Anti-Sm/RNP, like anti-dsDNA titers, seroconverted more frequently compared to anti-SS-A/SS-B. Furthermore, anti-Sm/RNP as well as anti-dsDNA titers, but not anti-SS-A/SS-B titers, fluctuated significantly compared to stable anti-VZV controls. Likewise, reductions in anti-dsDNA and anti-Sm/RNP titers after B cell depleting treatment were comparable in magnitude. However, only anti-dsDNA titer reductions associated with clinical outcomes.
Conclusions
Together, these results show that anti-Sm/RNP and anti-dsDNA, in contrast to anti-SS-A/SS-B, frequently fluctuate and their levels can decrease following B cell-targeted treatments. Thus, distinct ANAs have variable kinetics, potentially reflecting their derivation from different B cell differentiation pathways.
