Cell-Bound Complement Activation Products Correlate with Disease Activity in Childhood-Onset Systemic Lupus Erythematosus

Joyce Hui-Yuen¹, Derren Barken², John Conklin³, Tyler O'Malley⁴, Andrew Eichenfield⁵, Amy Starr⁶, Lisa F. Imundo⁷, Thierry Dervieux⁸ and Anca D. Askanase⁹, ¹North Shore-Long Island Jewish Health System, Lake Success, NY, ²Exagen Diagnostics, Inc., Vista, CA, ³1261 Liberty Way Suite C, Exagen Diagnostics, Vista, CA, ⁴Research and Development, Exagen Diagnostics, Vista, CA, ⁵Morgan Stanley Children's Hospital of NY-Presbyterian, Columbia University, New York, NY, ⁶Pediatric Rheumatology, Columbia University Medical Center, New York, NY, ⁷Assoociate Professor of Pediatrics in Medicine - Rheumatology, Columbia University Medical Center, New York, NY, ⁸Research and Development, Exagen Diagnostics, Inc., Vista, CA, ⁹Department of Medicine, Rheumatology, Columbia University College of Physicians & Surgeons, New York, NY

Meeting: 2016 ACR/ARHP Annual Meeting

Date of first publication: September 28, 2016

Keywords: Biomarkers, complement, pediatrics and systemic lupus erythematosus (SLE)

Session Information

Date: Tuesday, November 15, 2016

Title: Pediatric Rheumatology – Pathogenesis and Genetics - Poster

Session Type: ACR Poster Session C

Session Time: 9:00AM-11:00AM

Background/Purpose: Elevated levels of cell-bound complement activation products (C4d deposition on erythrocytes [EC4d] and B lymphocytes [BC4d], CB-CAPs) have been demonstrated to be sensitive and specific for the diagnosis of systemic lupus erythematosus (SLE) and C4d deposition on platelets (PC4d) to be specific for the diagnosis of SLE. We sought to evaluate the usefulness of CB-CAPs as a biomarker for disease activity in childhood-onset SLE (cSLE).

Methods: This is a longitudinal study of 28 patients with cSLE (diagnosed prior to their 19th birthdays) who fulfilled ACR-SLE classification criteria, with a mean follow-up of 6 months. Clinical and demographic data were recorded. Venous blood was collected every 3 months and shipped overnight to the reference clinical laboratory for the multi-analyte assay. The assay evaluates a full panel of autoantibodies, including anti-dsDNA, aPLs (beta-2 glycoprotein antibodies, aCL, and/or aPS-PT) and conventional serum complement levels (C3 and C4), as well as CB-CAPs; CB-CAPs results are reported as net mean fluorescence intensity (MFI). SpearmanÕs correlation was used to evaluate the correlation between CB-CAPs and disease activity scores; t-tests to evaluate the presence of CB-CAPs in APL patients.

Results: Clinical and demographic variables are presented in the Table. Mean SLEDAI was 4.3±3.8 (range 0-16). Elevated CB-CAPs correlated with SLEDAI scores in cSLE patients (r² range 0.23-0.38, p<0.05 for EC4d, BC4d, and PC4d, respectively) at baseline, 3 and 6 months. Higher levels of EC4d (>75 net MFI) were found to have better correlation with disease activity scores at all time-points (p<0.05). Additionally, in 11 cSLE patients with positive aPLs CB-CAPs were significantly elevated with p<0.05 for EC4d, but p=0.06 for BC4d and p=0.15 for PC4d; of note, C3 and C4 did not correlate with the presence of aPL in these patients (p=NS). Interestingly, several patients had normal levels of C3 and C4, but elevated CB-CAPs, possibly indicating fluctuating complement activation that was not captured by C3 and C4 measurements.

Conclusion: These pilot findings suggest that CB-CAPs could provide a useful biomarker for disease activity in cSLE, and may be particularly important in the monitoring of SLE patients with anti-phospholipid antibodies. Further longitudinal data is needed to establish CB-CAPs as a biomarker in cSLE and APS. Table: Patient demographics and results of CB-CAPs assays

	SLE (n=28)
Age (years)	18±2
Female %	75%
Duration of disease (years) Mean SLEDAI	4.7±3.2 4.3±3.8 (range 0-16)
Low Complement	50% (14/28)
ANA (IFA: ³1:80)	93% (26/28)
Anti-dsDNA (confirmed with Crithidia)	54% (15/28)
Anti-Smith	18% (5/28)
EC4d>14 net MFI	57% (16/28)
BC4d>60 net MFI PC4d>20 net MFI	63% (17/27) 29% (8/28)
Elevated CBCAPS (EC4d>14 net MFI, BC4d>60 net MFI, or PC4d >20 net MFI)	82% (23/28)

Disclosure: J. Hui-Yuen, None; D. Barken, Exagen, 3; J. Conklin, Exagen, 3; T. O'Malley, exagen, 3; A. Eichenfield, None; A. Starr, None; L. F. Imundo, None; T. Dervieux, Exagen, 3; A. D. Askanase, anca askanase, 2.

To cite this abstract in AMA style:

Hui-Yuen J, Barken D, Conklin J, O'Malley T, Eichenfield A, Starr A, Imundo LF, Dervieux T, Askanase AD. Cell-Bound Complement Activation Products Correlate with Disease Activity in Childhood-Onset Systemic Lupus Erythematosus [abstract]. Arthritis Rheumatol. 2016; 68 (suppl 10). https://acrabstracts.org/abstract/cell-bound-complement-activation-products-correlate-with-disease-activity-in-childhood-onset-systemic-lupus-erythematosus/. Accessed .

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