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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%).

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.

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Indicators of disease and cumulative disease activity in pediatric- and adult-onset systemic lupus erythematosus (pSLE and aSLE). (A) Circulating plasma osteopontin (cOPN) and neutrophil gelatinase-associated lipocalin (cNGAL) levels in pSLE and aSLE are increased compared with unrelated age-matched healthy young controls (H.C.) and unrelated healthy adults (H.A.), respectively. pSLE patients with active disease are represented by open squares. (B) Increased 6-month adjusted-mean SLE disease activity index (AMS) is seen in pSLE and aSLE patients who have an increase in Systemic Lupus International Collaborating Clinics/American College of Rheumatology (SLICC/ACR) damage index scores (SDI) at the end of the 12-month follow up period.
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Figure 1: Indicators of disease and cumulative disease activity in pediatric- and adult-onset systemic lupus erythematosus (pSLE and aSLE). (A) Circulating plasma osteopontin (cOPN) and neutrophil gelatinase-associated lipocalin (cNGAL) levels in pSLE and aSLE are increased compared with unrelated age-matched healthy young controls (H.C.) and unrelated healthy adults (H.A.), respectively. pSLE patients with active disease are represented by open squares. (B) Increased 6-month adjusted-mean SLE disease activity index (AMS) is seen in pSLE and aSLE patients who have an increase in Systemic Lupus International Collaborating Clinics/American College of Rheumatology (SLICC/ACR) damage index scores (SDI) at the end of the 12-month follow up period.

Mentions: Patients with pSLE were evaluated at baseline for several parameters by cross-sectional analysis. cOPN was increased in the total pSLE sample compared with healthy, unrelated age-matched controls (ages 17 to 22 years; mean ± SD: 20.3 ± 1.3 years): median 5.7 ng/ml in controls vs. 8.8 ng/ml in pSLE (P = 0.03) (Figure 1A). Similar results were seen when comparing cOPN in aSLE with healthy, unrelated age-matched controls: median 7.5 ng/ml in controls vs. 13.0 ng/ml in aSLE (P = 0.02) Figure 1A). cNGAL was also increased at baseline in both the pSLE cohort and the aSLE cohort compared with the age-matched controls: 17.7 ng/ml in controls vs. 23.5 ng/ml in pSLE (P = 0.02); 21.0 ng/ml in controls vs. 31.7 ng/ml in aSLE (P = 0.04).


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)

Indicators of disease and cumulative disease activity in pediatric- and adult-onset systemic lupus erythematosus (pSLE and aSLE). (A) Circulating plasma osteopontin (cOPN) and neutrophil gelatinase-associated lipocalin (cNGAL) levels in pSLE and aSLE are increased compared with unrelated age-matched healthy young controls (H.C.) and unrelated healthy adults (H.A.), respectively. pSLE patients with active disease are represented by open squares. (B) Increased 6-month adjusted-mean SLE disease activity index (AMS) is seen in pSLE and aSLE patients who have an increase in Systemic Lupus International Collaborating Clinics/American College of Rheumatology (SLICC/ACR) damage index scores (SDI) at the end of the 12-month follow up period.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 1: Indicators of disease and cumulative disease activity in pediatric- and adult-onset systemic lupus erythematosus (pSLE and aSLE). (A) Circulating plasma osteopontin (cOPN) and neutrophil gelatinase-associated lipocalin (cNGAL) levels in pSLE and aSLE are increased compared with unrelated age-matched healthy young controls (H.C.) and unrelated healthy adults (H.A.), respectively. pSLE patients with active disease are represented by open squares. (B) Increased 6-month adjusted-mean SLE disease activity index (AMS) is seen in pSLE and aSLE patients who have an increase in Systemic Lupus International Collaborating Clinics/American College of Rheumatology (SLICC/ACR) damage index scores (SDI) at the end of the 12-month follow up period.
Mentions: Patients with pSLE were evaluated at baseline for several parameters by cross-sectional analysis. cOPN was increased in the total pSLE sample compared with healthy, unrelated age-matched controls (ages 17 to 22 years; mean ± SD: 20.3 ± 1.3 years): median 5.7 ng/ml in controls vs. 8.8 ng/ml in pSLE (P = 0.03) (Figure 1A). Similar results were seen when comparing cOPN in aSLE with healthy, unrelated age-matched controls: median 7.5 ng/ml in controls vs. 13.0 ng/ml in aSLE (P = 0.02) Figure 1A). cNGAL was also increased at baseline in both the pSLE cohort and the aSLE cohort compared with the age-matched controls: 17.7 ng/ml in controls vs. 23.5 ng/ml in pSLE (P = 0.02); 21.0 ng/ml in controls vs. 31.7 ng/ml in aSLE (P = 0.04).

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