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

Rullo OJ, Woo JM, Parsa MF, Hoftman AD, Maranian P, Elashoff DA, Niewold TB, Grossman JM, Hahn BH, McMahon M, McCurdy DK, Tsao BP - Arthritis Res. Ther. (2013)

Bottom Line: Compared 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).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%).

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ABSTRACT

Introduction: Osteopontin (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.

Methods: cOPN 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).

Results: Compared 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%).

Conclusion: High 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.

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Baseline circulating osteopontin levels correlated with disease-related damage accumulated over the subsequent twelve months. Mean baseline natural log-transformed circulating osteopontin (lncOPN) was higher in pediatric- and adult-onset systemic lupus erythematosus (pSLE and aSLE) patients who had an increase in (SDI) scores over the 12-month study period (left), but not mean natural log-transformed circulating neutrophil gelatinase-associated lipocalin (lncNGAL) (right). SDI, Systemic Lupus International Collaborating Clinics/American College of Rheumatology (SLICC/ACR) damage index.
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Figure 3: Baseline circulating osteopontin levels correlated with disease-related damage accumulated over the subsequent twelve months. Mean baseline natural log-transformed circulating osteopontin (lncOPN) was higher in pediatric- and adult-onset systemic lupus erythematosus (pSLE and aSLE) patients who had an increase in (SDI) scores over the 12-month study period (left), but not mean natural log-transformed circulating neutrophil gelatinase-associated lipocalin (lncNGAL) (right). SDI, Systemic Lupus International Collaborating Clinics/American College of Rheumatology (SLICC/ACR) damage index.

Mentions: At the baseline visit, bivariate analysis revealed pSLE patients with any organ damage (SDI > 0; n = 16) had increased cOPN levels compared with pSLE patients with no damage (median 18.5 ng/ml in SDI > 0 vs. 6.6 ng/ml in SDI = 0 at enrollment, P = 0.02). In addition, SDI scores at enrollment correlated with increased cOPN (r = 0.43, P = 0.005). Of 42 pSLE patients, 7 (16%) had an increase in SDI over the 12-month study period, which was also associated with increased baseline cOPN (P = 0.007) (Figure 3, top left panel); a similar trend was seen in aSLE patients (P = 0.075) (Figure 3, top left panel) and a combined analysis of pSLE with aSLE demonstrated statistical significance (P = 0.001) (Figure 3, bottom left panel). There was no difference in baseline cNGAL in pSLE or aSLE with an increased SDI, although a combined analysis of pSLE and aSLE demonstrated a trend of lower cNGAL at baseline in those individuals with an increase in SDI over the study period (Figure 3, right panels).


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

Rullo OJ, Woo JM, Parsa MF, Hoftman AD, Maranian P, Elashoff DA, Niewold TB, Grossman JM, Hahn BH, McMahon M, McCurdy DK, Tsao BP - Arthritis Res. Ther. (2013)

Baseline circulating osteopontin levels correlated with disease-related damage accumulated over the subsequent twelve months. Mean baseline natural log-transformed circulating osteopontin (lncOPN) was higher in pediatric- and adult-onset systemic lupus erythematosus (pSLE and aSLE) patients who had an increase in (SDI) scores over the 12-month study period (left), but not mean natural log-transformed circulating neutrophil gelatinase-associated lipocalin (lncNGAL) (right). SDI, Systemic Lupus International Collaborating Clinics/American College of Rheumatology (SLICC/ACR) damage index.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3672798&req=5

Figure 3: Baseline circulating osteopontin levels correlated with disease-related damage accumulated over the subsequent twelve months. Mean baseline natural log-transformed circulating osteopontin (lncOPN) was higher in pediatric- and adult-onset systemic lupus erythematosus (pSLE and aSLE) patients who had an increase in (SDI) scores over the 12-month study period (left), but not mean natural log-transformed circulating neutrophil gelatinase-associated lipocalin (lncNGAL) (right). SDI, Systemic Lupus International Collaborating Clinics/American College of Rheumatology (SLICC/ACR) damage index.
Mentions: At the baseline visit, bivariate analysis revealed pSLE patients with any organ damage (SDI > 0; n = 16) had increased cOPN levels compared with pSLE patients with no damage (median 18.5 ng/ml in SDI > 0 vs. 6.6 ng/ml in SDI = 0 at enrollment, P = 0.02). In addition, SDI scores at enrollment correlated with increased cOPN (r = 0.43, P = 0.005). Of 42 pSLE patients, 7 (16%) had an increase in SDI over the 12-month study period, which was also associated with increased baseline cOPN (P = 0.007) (Figure 3, top left panel); a similar trend was seen in aSLE patients (P = 0.075) (Figure 3, top left panel) and a combined analysis of pSLE with aSLE demonstrated statistical significance (P = 0.001) (Figure 3, bottom left panel). There was no difference in baseline cNGAL in pSLE or aSLE with an increased SDI, although a combined analysis of pSLE and aSLE demonstrated a trend of lower cNGAL at baseline in those individuals with an increase in SDI over the study period (Figure 3, right panels).

Bottom Line: Compared 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).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%).

View Article: PubMed Central - HTML - PubMed

ABSTRACT

Introduction: Osteopontin (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.

Methods: cOPN 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).

Results: Compared 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%).

Conclusion: High 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.

Show MeSH
Related in: MedlinePlus