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Abstract Number: 1608

Erythrocyte C4d and Antibodies to Anti-C1q Are Associated with Proteinuria in Lupus Nephritis

Jill P. Buyon1, R. Ramsey-Goldman2, Richard Furie3, Chaim Putterman4, Kenneth Kalunian5, John Conklin6, Tyler O'Malley7, Derren Barken8 and Thierry Dervieux9, 1Department of Medicine, Division of Rheumatology, New York University School of Medicine, New York, NY, 2Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, 3Division of Rheumatology, North Shore-LIJ Health System, Great Neck, NY, 4The Division of Rheumatology, Albert Einstein College of Medicine, Bronx, NY, 5UCSD School of Medicine, La Jolla, CA, 61261 Liberty Way Suite C, Exagen Diagnostics, Inc., Vista, CA, 7Research and Development, Exagen Diagnostics, Inc., Vista, CA, 8Exagen Diagnostics, Inc., Vista, CA, 9rd, Exagen Diagnostics, Inc., Vista, CA

Meeting: 2014 ACR/ARHP Annual Meeting

Keywords: Biomarkers and systemic lupus erythematosus (SLE), Disease Activity

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Session Information

Title: Systemic Lupus Erythematosus - Human Etiology and Pathogenesis: Autoimmune Disease Transition, Disease Subsets and Prediction of Flares, Cytokines and Autoantibodies

Session Type: Abstract Submissions (ACR)

Background/Purpose: Biomarkers of renal response in patients with systemic lupus erythematosus (SLE) may provide clues to pathogenesis and drive translation to treatment.  This study was initiated to evaluate the association between renal activity and the changes in erythrocyte bound complement C4d product (EC4d), anti-C1q, anti-dsDNA antibodies and low complement.

Methods: The study enrolled 289 SLE patients (mean age 40 years, 92% females) meeting the 1982 ACR classification criteria.  All patients were evaluated at one time point as part of a cross-sectional study and a subset of 34 patients (mean age 34 years, 94% female) were followed monthly for an average of 9 months. Among patients enrolled in the cross sectional study, the presence of proteinuria was defined by the renal domain on the SELENA-SLEDAI (increase >0.5 g thus implies active and not chronic proteinuria). For the longitudinal study, proteinuria was defined using the random protein to creatinine ratio (expressed as g/g). Complement protein levels (C3 and C4) were determined using immunoturbidimetry, antibodies to anti-C1q and anti-dsDNA were determined by ELISA and EC4d was determined using flow cytometry (expressed as mean fluorescence intensity [MFI]). Statistical analyses consisted of non-parametric tests, and Chi-square tests. Longitudinal changes in urine protein as a function of the change in the biomarkers were evaluated using generalized linear mixed models effects using random intercept and fixed slopes.

Results: Among 289 SLE, 12% presented with proteinuria at the time of the clinical assessment. Higher EC4d levels were observed in the SLE patients who presented with proteinuria compared to those who did not (median 21 MFI [Interquartile range, IQR: 15-29] vs 12 MFI [IQR: 7-22], p<0.01). Abnormal EC4d levels (>20 MFI) were found in 62% of patients with proteinuria compared to 27% of patients without (p<0.001). In contrast, the presence of the low complement component of the SELENA-SLEDAI domain was not significantly different between the groups (53% versus 36% p=0.08). Neither Anti-C1q nor anti-dsDNA antibodies differentiated between the two groups at baseline.  Among the 34 SLE patients followed monthly, a decrease in EC4d levels to lower than 20 MFI was associated with a concomitant decrease of 0.7 g/g urine protein to creatinine ratio (p=0.0018) (Table). Similarly, the decrease in anti-C1q levels to lower than 80 units was accompanied by decreased proteinuria (p=0.0015). Normalization of low complement or loss of anti-dsDNA was non-significantly associated with proteinuria (p>0.19). In multivariate analysis both EC4d and anti-C1q were independently associated with proteinuria (p<0.01).

Conclusion: These data suggest that longitudinal changes in EC4d and anti-C1q levels track with   changes in proteinuria. EC4d correlates more strongly with proteinuria than traditional measures of complement.

Table: Mixed model effect estimates

 

Estimate (SEM) g/g

P value

EC4d≤20 MFI

-0.70±0.22

0.0018

Anti-C1q≤80 units

-1.12 ±0.35

0.0015

Normal Complement (C3/C4)

-0.33±0.24

0.19

Loss of Anti-dsDNA

+0.07±0.29

0.81


Disclosure:

J. P. Buyon,

Exagen,

2;

R. Ramsey-Goldman,

Exagen,

2;

R. Furie,

Exagen,

2;

C. Putterman,

Exagen,

2,

Exagen,

5;

K. Kalunian,

Exagen,

2,

Exagen,

5;

J. Conklin,

Exagen,

3;

T. O’Malley,

Exagen,

3;

D. Barken,

Exagen,

3;

T. Dervieux,
None.

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