Abstract
Purpose Predicting flares and disease progression, including the development of lupus nephritis (LN), a major and sometimes fatal clinical manifestation, remains challenging in patients with systemic lupus erythematosus (SLE). Several previous cross-sectional studies have suggested osteopontin (OPN) as a putative SLE biomarker, but longitudinal studies assessing its diagnostic accuracy are lacking. Therefore, we aimed to investigate the usefulness of measuring plasma levels of OPN (P-OPN) longitudinally in patients with SLE, to evaluate its association over time with relevant clinical manifestations, such as active LN and disease activity.
Methods A cohort of 69 patients with an established SLE diagnosis underwent follow-up for a period of at least 4 months. We collected clinical data and laboratory data every 60 ± 20 days, and we assessed disease activity, using SLEDAI-2K scores, at each visit (Table 1). We measured P-OPN levels by ELISA in 1013 samples (Table 2). We calculated the area under the ROC curve (AUC) to assess the diagnostic accuracy of P-OPN for relevant clinical manifestations. We used Youden’s index to determine adequate cut-off levels for P-OPN. We also analyzed the temporal relationships between increased P-OPN levels and the prevalence of LN.
Results Increased levels of P-OPN were found in 205 samples from 39 patients during the longitudinal study. High P-OPN levels correlated with increased disease activity, defined as SLEDAI-2K scores above 3 (p <0.01) and with active LN (p <0.01). High levels of P-OPN were associated with forthcoming LN (OR = 4.46; p = 0.004) with AUC 0.69 (Figure 1A). A cut-off value of 76.5 ng/ml predicted LN within 60 ± 20 days, with specificity (Sp) of 0.78 and sensitivity (Se) of 0.56. In combination with positive anti-dsDNA antibodies, a P-OPN threshold of 82.8 ng/ml predicted forthcoming LN within 60 ± 20 days, with Sp of 0.88 and Se of 0.72 (Figure 1B).
Conclusion Measurement of P-OPN levels can facilitate the identification of patients predicted to develop LN, especially when combined with positive anti-dsDNA antibodies. P-OPN may be a useful complementary tool in clinical practice, to tailor the treatment of patients with SLE. Future studies are warranted to evaluate the potential role of OPN in LN pathogenesis.
