Arthritis & Rheumatism, Volume 62,
November 2010 Abstract Supplement

Abstracts of the American College of
Rheumatology/Association of Rheumatology Health Professionals
Annual Scientific Meeting
Atlanta, Georgia November 6-11, 2010.


Biomarkers for Global and Renal Disease Activity in Juvenile Systemic Lupus Erythematosus (jSLE).

Mina4,  Rina, Bennett3,  Michael, Ahearn1,  Joseph M., Pendl3,  Joshua, Eaton3,  Jamie, Wilson5,  Nicole, Devarajan3,  Prasad

Wexford, PA
Cincinnati Child Hosp Med Ctr, Cincinnati, OH
Cincinnati Children's Hospital Medical Center
Cincinnati Children's Med Ctr, Cincinnati, OH
Univerisity of Pittsburgh

Background:

Preliminary data suggest that the Lupus Nephritis Renal Panel (LNRP), composed of transferrin, ceruloplasmin, acid-1-glycoprotein, neutrophil gelatinase-associated lipocalin, prostaglandin-D synthethase and monocyte chemotactic protein1, is associated with worsening lupus nephritis in jSLE. Cell-bound complement activated products (CB-CAP) which consist of erythrocyte, reticulocyte and platelet-bound complement components (E-C4d, E-C3d E-fBb, E-CR1, R-C4d, R-C3d, R-fBb and P-C4d) have been shown to reflect ongoing global disease activity in studies limited to adults with SLE.

Objectives:

Evaluate the association of the LNRP and CB-CAP with global and renal disease activity in jSLE.

Methods:

Clinical, laboratory and biomarker data were collected from 12 jSLE patients during initial and follow-up visits. Levels of LNRP standardized to urine creatinine and CB-CAP were measured by enzyme-linked immunosorbent assay and flow cytometry respectively. Physician-rated change in patient's disease course between visits (global/renal disease worsening: yes/no) served as the criterion standard.

Results:

Using Wilcoxon Rank Sum Test and Spearman's correlation, statistically significant association was seen between levels of specific urine biomarkers and the renal domains of disease activity indices and the criterion standard (see Table 1). Levels of urine biomarkers were seen to be elevated three months prior to renal worsening with the change in the biomarker level associated with the change in the renal disease activity scores. No significant correlation between extra-renal disease activity and urine biomarkers was seen. Of the CB-CAP, E-CR1, P-C4d and R-C4d were associated with current global/extra-renal disease activity. Traditional biomarkers for global and renal worsening correlated poorly with disease course and activity.

Correlation of Biomarkers with Disease Variables¶

  Concurrent validity Predictive validity
Biomarker¶¶Disease variablerp-valueDisease variablerp-value
CeruloplasminRenal BILAG0.610.02Renal SLAM0.700.02
 Renal SLEDAI0.600.01Renal BILAG0.690.02
Monocyte chemotactic protein1Renal SLAM0.600.01Extra renal BILAG-0.600.05
 Renal SLEDAI0.750.0008   
TransferrinRenal SLAM0.560.02Renal SLAM0.780.01
 Renal BILAG0.720.003Renal BILAG0.750.01
Prostaglandin-D synthethaseRenal SLEDAI0.750.0005Renal SLEDAI0.640.05
 Renal BILAG0.660.01Renal BILAG0.660.03
Acid-1-glycoproteinRenal BILAG0.610.02Renal BILAG0.620.04
Erythrocyte complement receptor1Total/Extra-renal BILAG-0.530.02Urine protein/creatinine-0.300.04
Erythrocyte-factor BbRenal BILAG-0.520.04Creatinine clearance0.620.03
Reticulocyte bound-C4dTotal/Extra-renal BILAG0.720.04   
Platelet bound C4dTotal/Extra-renal BILAG0.89<0.0001   
##Legend: ¶Only significant correlation shown ¶¶Urine biomarkers standardized to urine creatinine

Conclusions:

LNRP is associated with renal disease activity and CB-CAP with extra-renal disease activity in jSLE. Further studies assessing the predictive properties of combining these biomarkers are in progress.

To cite this abstract, please use the following information:
Mina, Rina, Bennett, Michael, Ahearn, Joseph M., Pendl, Joshua, Eaton, Jamie, Wilson, Nicole, et al; Biomarkers for Global and Renal Disease Activity in Juvenile Systemic Lupus Erythematosus (jSLE). [abstract]. Arthritis Rheum 2010;62 Suppl 10 :2106
DOI: 10.1002/art.29871

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