Plasma levels of osteopontin identify patients at risk for organ damage in systemic lupus erythematosus

Abstract

IntroductionOsteopontin (OPN) has been implicated as a mediator of Th17 regulation via type I interferon (IFN) receptor signaling and in macrophage activity at sites of tissue repair. This study assessed whether increased circulating plasma OPN (cOPN) precedes development of organ damage in pediatric systemic lupus erythematosus (pSLE) and compared it to circulating plasma neutrophil gelatinase-associated lipocalin (cNGAL), a predictor of increased SLE disease activity.MethodscOPN and cNGAL were measured in prospectively followed pSLE (n = 42) and adult SLE (aSLE; n = 23) patients and age-matched controls. Time-adjusted cumulative disease activity and disease damage were respectively assessed using adjusted-mean SLE disease activity index (SLEDAI) (AMS) and SLICC/ACR damage index (SDI).ResultsCompared to controls, elevated cOPN and cNGAL were observed in pSLE and aSLE. cNGAL preceded worsening SLEDAI by 3-6 months (P = 0.04), but was not associated with increased 6-month AMS. High baseline cOPN, which was associated with high IFNalpha activity and expression of autoantibodies to nucleic acids, positively correlated with 6-month AMS (r = 0.51 and 0.52, P = 0.001 and 0.01 in pSLE and aSLE, respectively) and was associated with SDI increase at 12 months in pSLE (P = 0.001). Risk factors for change in SDI in pSLE were cOPN (OR 7.5, 95% CI [2.9-20], P = 0.03), but not cNGAL, cumulative prednisone, disease duration, immunosuppression use, gender or ancestry using univariate and multivariate logistic regression. The area under the curve (AUC) when generating the receiver-operating characteristic (ROC) of baseline cOPN sensitivity and specificity for the indication of SLE patients with an increase of SDI over a 12 month period is 0.543 (95% CI 0.347-0.738; positive predictive value 95% and negative predictive value 38%).ConclusionHigh circulating OPN levels preceded increased cumulative disease activity and organ damage in SLE patients, especially in pSLE, and its value as a predictor of poor outcome should be further validated in large longitudinal cohorts.

Role of Osteopontin in Systemic Lupus Erythematosus

“…In patients with renal disease, there was a positive correlation between IL-18 and OPN concentration ( p < 0.001). Also our study agreed with Rullo et al (22) who found that increased circulating plasma OPN levels may be associated with organ damage in 42 pediatric SLE and 23 adult SLE. Plasma OPN concentrations were significantly higher in both groups than in controls and showed a positive correlation between OPN and SLEDAI in six months.…”

Soluble urokinase plasminogen activator receptor levels reflect organ damage in systemic lupus erythematosus

“…To our knowledge, no biomarkers apart from lymphocyte Fas expression, 14 sFas, 12 CRP 13 , and osteopontin 15 have been shown to associate with organ damage as defined by SDI.…”

“…apoptosis stimulating fragment (Fas/CD95), both membrane bound and soluble (sFas), CRP and osteopontin), and organ damage. [12][13][14][15] However, only plasma levels of osteopontin have been shown predict organ damage, and this was shown for a relatively small study group of SLE patients. 15 Soluble urokinase plasminogen activator receptor (suPAR) is part of the plasminogen activation system and is involved in inflammation, tissue remodeling and cancer metastasis.…”

“…[12][13][14][15] However, only plasma levels of osteopontin have been shown predict organ damage, and this was shown for a relatively small study group of SLE patients. 15 Soluble urokinase plasminogen activator receptor (suPAR) is part of the plasminogen activation system and is involved in inflammation, tissue remodeling and cancer metastasis. 16 Many cell types express uPAR (CD87), including vascular smooth muscle cells, 17 16,27 In the first studies on circulating suPAR, levels were found to be elevated and to predict disease outcome in various forms of cancer and infectious diseases.…”

Osteopontin (OPN) Gene Polymorphisms and Autoimmune Diseases

“…It has been demonstrated that serum OPN level is elevated in SLE patients [31][32][33][34][35][36]. Moreover, OPN level correlates positively with disease activity index [33][34][35]. Polymorphic OPN alleles have been implicated in the mouse model of lupus [37].…”