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.
This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/.
Statistics from Altmetric.com
If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.