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Abstract Number: 1797

A Multianalyte Assay Panel (MAP) with Algorithm Containing Cell-Bound Complement Activation Products (CB-CAPs) Is Superior to Anti-dsDNA and Low Serum Complement Levels in Predicting Transition of Probable Lupus to ACR Classified Lupus Within 2 Years

Rosalind Ramsey-Goldman1, Roberta Vezza Alexander2, Cristina Arriens3, Sonali Narain4, Elena Massarotti5, Daniel J Wallace6, Amit Saxena7, Christopher Collins8, Chaim Putterman9, Kenneth Kalunian10, Armida Sace2, Rowena LaFon2, JoAnne Ligayon2, John Conklin11 and Arthur Weinstein12, 1Division of Rheumatology, Northwestern University Feinberg School of Medicine, Chicago, IL, 2Exagen Inc, Vista, CA, 3Oklahoma Medical Research Foundation, Oklahoma City, OK, 4Northwell Health, Great Neck, NY, 5Brigham and Women's Hospital, Boston, MA, 6Cedars-Sinai Medical Center, Beverly Hills, CA, 7NYU School of Medicine, New York, 8MedStar Washington Hospital Center, Washington, DC, 9Albert Einstein College of Medicine, Bronx, NY, 10University of California San Diego, La Jolla, CA, 11Exagen Inc., Vista, CA, 12Loma Linda University and Exagen, Inc, Claremont, CA

Meeting: ACR Convergence 2020

Keywords: Biomarkers, complement, Systemic lupus erythematosus (SLE)

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Session Information

Date: Monday, November 9, 2020

Title: SLE – Diagnosis, Manifestations, & Outcomes Poster III: Bench to Bedside

Session Type: Poster Session D

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

Background/Purpose: We reported previously (Ramsey-Goldman et al., Arthritis Rheumatol 2020) that score > 0.8 of a multianalyte assay panel (MAP) with algorithm predicts fulfillment of a 4th ACR criterion 9-18 months (median 12) after enrollment in patients with probable systemic lupus erythematosus (pSLE). We continued to follow pSLE to better evaluate transition to classifiable SLE.

Methods: pSLE, defined as fulfilling 3 ACR criteria, were followed at academic lupus centers. At enrollment, 35 (38%) of the 92 pSLE fulfilled SLICC criteria. CB-CAPs – C4d bound to erythrocytes (EC4d) and B-cells (BC4d) – were measured by quantitative flow cytometry, serum C3 and C4 by turbidimetry, and autoantibodies by ELISA. Anti-dsDNA positivity was confirmed by immunofluorescence (IFA). MAP index consists of an algorithm with CB-CAPs and autoantibodies (Dervieux et al., J Immunol Methods 2017). Initial decision analysis with Youden index showed that MAP > 0.8 and EC4d > 20 mean fluorescence intensity units (MFI) reflected the optimal cutoffs for transition to ACR classifiable SLE; the same cutoffs were used for analysis of all follow-up visits. Time to fulfillment of ACR criteria was evaluated by Kaplan-Meier analysis; associations were analyzed by log-rank test and Cox proportional hazards model and are expressed as hazards ratio (HR).

Results: Of the 92 pSLE, 74 had 1 or 2 follow-up visits 9-35 months after enrollment for a total of 128 visits. Overall, 28 pSLE (30.4%) transitioned to ACR classifiable SLE: 16 (57%) in the 1st year and 12 (43%) in the 2nd. The clinical or laboratory features that defined fulfillment of ACR criteria are in Table 1. Use of hydroxychloroquine and immunosuppressants was similar in those who did and did not transition to SLE. Of the 17 subjects who accrued hematological criteria during the study (11 as the sole criterion and 6 as one of the new criteria), a minority were on immunosuppressants: 6 at enrollment, 5 at the 1st visit, and 3 at the 2nd. Neither SLICC criteria nor individual biomarkers were significantly associated with transition to SLE (Table 2). Only MAP > 0.8 had significantly high HR for transition to SLE;  EC4d > 20 MFI, low complement, and anti-dsDNA were not significant (Table 2).

Conclusion: The majority of pSLE transitioned within a year. MAP > 0.8 predicted disease evolution into classifiable SLE better than other biomarkers or fulfillment of SLICC criteria.

Table 1. Clinical and laboratory features leading to the transition of pSLE to SLE. The 16 individuals who fulfilled ACR criteria within 1 year (≤365 days) accrued a total of 22 new ACR criteria, with hematological being the most common. The 12 subjects who fulfilled ACR criteria after the 1st year of follow up (>365 days) accrued a total of 15 criteria, with hematological being again the most common. Of note, 2 subjects who fulfilled ACR criteria within 12 months accrued additional criteria after this time point (an immunological criterion and ulcers); these criteria are included in the table.

Table 2. Hazard ratio (HR) of variables measured at enrollment in predicting fulfillment of ACR classification criteria in the pSLE population. Data of 128 follow-up visits (n=127 for MAP) that occurred 9 to 35 months after enrollment were analyzed. CB-CAPs: cell-bound complement activation products; MAP: multianalyte assay panel with algorithm; HR: hazard ratio; CI: confidence intervals.


Disclosure: R. Ramsey-Goldman, None; R. Alexander, Exagen Inc, 1; C. Arriens, BMS, 1, 2, GSK, 1; S. Narain, None; E. Massarotti, Exagen, 1, EMD Serono, 1; D. Wallace, Exagen, 1, 2, Exagen, 1, 2; A. Saxena, Glaxo Smith Kline, 1, Bristol Myers Squibb, 1; C. Collins, GSK, 1, Abbvie, 1, 2, Novartis, 1, Exagen, 1, 2; C. Putterman, Equillium, 1, 2; K. Kalunian, Roche, 5, Biogen, 5, Janssen, 5, AstraZeneca, 5, Lupus Research Alliance, 2, Pfizer, 2, Sanford Consortium, 2, Eli Lilly, 5, Genetech, 5, Gilead, 5, ILTOO, 5, Nektar, 5, Viela, 5, Equillium, 5, Bristol-Meyers Squibb, 5; A. Sace, None; R. LaFon, None; J. Ligayon, Exagen Inc, 1; J. Conklin, Exagen, 1, 2; A. Weinstein, Exagen, 1, 2.

To cite this abstract in AMA style:

Ramsey-Goldman R, Alexander R, Arriens C, Narain S, Massarotti E, Wallace D, Saxena A, Collins C, Putterman C, Kalunian K, Sace A, LaFon R, Ligayon J, Conklin J, Weinstein A. A Multianalyte Assay Panel (MAP) with Algorithm Containing Cell-Bound Complement Activation Products (CB-CAPs) Is Superior to Anti-dsDNA and Low Serum Complement Levels in Predicting Transition of Probable Lupus to ACR Classified Lupus Within 2 Years [abstract]. Arthritis Rheumatol. 2020; 72 (suppl 10). https://acrabstracts.org/abstract/a-multianalyte-assay-panel-map-with-algorithm-containing-cell-bound-complement-activation-products-cb-caps-is-superior-to-anti-dsdna-and-low-serum-complement-levels-in-predicting-transition-of-pro/. Accessed .
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