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


CONCLUSIONS
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.
Ornella J
OJ
Rullo
Jennifer M P
JM
Woo
Miriam F
MF
Parsa
Alice D C
AD
Hoftman
Paul
P
Maranian
David A
DA
Elashoff
Timothy B
TB
Niewold
Jennifer M
JM
Grossman
Bevra H
BH
Hahn
Maureen
M
McMahon
Deborah K
DK
McCurdy
Betty P
BP
Tsao
D000209:Acute-Phase Proteins; D000293:Adolescent; D000328:Adult; D002648:Child; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D000071068:Lipocalin-2; D054834:Lipocalins / Q000097:blood; D008180:Lupus Erythematosus, Systemic / Q000097:blood* / Q000473:pathology*; D008297:Male; D053495:Osteopontin / Q000097:blood*; D011518:Proto-Oncogene Proteins / Q000097:blood; D012680:Sensitivity and Specificity; D012720:Severity of Illness Index
D000209:Acute-Phase Proteins; C489506:LCN2 protein, human; D000071068:Lipocalin-2; D054834:Lipocalins; D011518:Proto-Oncogene Proteins; D053495:Osteopontin