Cell Bound Complement Activation Products Distinguish Systemic Lupus Erythematosus from Other Diseases Among Patients with High Antinuclear Antibody Titers and Normal Complement

Daniel J. Wallace¹, Elena Massarotti², Rosalind Ramsey-Goldman³, Christopher E. Collins⁴, Anca Askanase⁵, Jill P. Buyon⁶, Richard Furie⁷, Sonali Narain⁷, Amit Saxena⁸, Kenneth C. Kalunian⁹, Cristina Arriens¹⁰, Chaim Putterman¹¹, John Conklin¹², Roberta Alexander¹², Claudia Ibarra¹², Tyler O'Malley¹³, Tarun Chandra¹⁴, Joseph Ahearn¹⁵, Susan Manzi¹⁶, Arthur Weinstein¹⁷ and Thierry Dervieux¹², ¹Cedars-Sinai Medical Center, UCLA, Los Angeles, CA, ²Brigham and Women's Hospital, Boston, MA, ³FSM, Northwestern University, Chicago, IL, ⁴Rheumatology, MedStar Washington Hospital Center, Washington, DC, ⁵Department of Medicine, Rheumatology, Columbia University College of Physicians & Surgeons, New York, NY, ⁶Rheumatology, NYU Langone Medical Center, New York, NY, ⁷Northwell Health, Great Neck, NY, ⁸NYU Langone Medical Center, New York, NY, ⁹Division of Rheumatology, Allergy and Immunology, UCSD School of Medicine, La Jolla, CA, ¹⁰Arthritis & Clinical Immunology, Oklahoma Medical Research Foundation, Oklahoma City, OK, ¹¹Division of Rheumatology, Albert Einstein College of Medicine, Bronx, NY, USA, Bronx, NY, ¹²Exagen Diagnostics, Inc., Vista, CA, ¹³Research and Development, Exagen Diagnostics, Inc., Vista, CA, ¹⁴EmpiriQA LLC, Long Grove, IL, ¹⁵Lupus Center of Excellence, West Penn Allegheny Health System, Pittsburgh, PA, ¹⁶Medicine, Allegheny Health Network, Pittsburgh, PA, ¹⁷Rheumatology, MedStar Washington Hospital Center/Georgetown University Medical Center, Washington, DC

Meeting: 2017 ACR/ARHP Annual Meeting

Date of first publication: September 18, 2017

Keywords: ANA, complement and systemic lupus erythematosus (SLE)

Session Information

Date: Sunday, November 5, 2017

Title: Systemic Lupus Erythematosus – Clinical Aspects and Treatment Poster I: Biomarkers and Outcomes

Session Type: ACR Poster Session A

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

Background/Purpose: Patients are often referred to the rheumatologist because of elevated anti-nuclear antibody (ANA) titers. We sought to evaluate the association of cell bound complement activation products (CB-CAPs), low complement (C3 or C4), and anti-double stranded (ds) DNA with systemic lupus erythematosus (SLE) and ANA titers.

Methods: The cohort (n=1155 adults) consisted of 498 patients with SLE with established disease (all fulfilling the 1997 ACR criteria, 91% females, mean age 41 years) pooled from prior studies of complement activation products, and a control group of 657 subjects (86% females; mean age 56 years; 314 with rheumatoid arthritis and 343 with other diseases). Abnormal CB-CAPs consisted of C4d bound to erythrocyte or B-lymphocyte levels above the 99th percentile of normal healthy. Low complement (C3 or C4) and anti-dsDNA (all confirmed using Crithidia luciliae) were determined using immunoassays. ANA titers were determined by indirect immunofluorescence, with subjects classified as having negative (<1:80), intermediate (1:80 to 1:320) or high (≥1:640) ANA status. The sensitivity, specificity, and Youden’s index (J), a measure of diagnostic effectiveness that combines sensitivity and specificity (J = sensitivity + specificity – 1) of various markers in distinguishing SLE from non-SLE, were evaluated. J differences were tested using t-tests.

Results: The diagnostic effectiveness of abnormal CB-CAPs, low complement, and anti-dsDNA in distinguishing SLE from non-SLE is presented in the Table. Overall, abnormal CB-CAPs had a significantly greater association with SLE (J=0.51) than low complement (J=0.32) and anti-dsDNA (J=0.31) (p<0.01; n=1155). The greater association of abnormal CB-CAPs in comparison to low complement and anti-dsDNA was statistically significant in the group of subjects with high ANA (p<0.03), intermediate ANA (p<0.01), and negative ANA (p<0.02). This association was also seen among subjects with high ANA (J=0.60) compared to intermediate (J=0.45) and negative ANA (J=0.17) (p<0.01). Similar results were observed for low complement and anti-dsDNA (p<0.01). In the group of subjects with normal complement (309 SLE and 619 non SLE), abnormal CB-CAPs was 50% sensitive and 89% specific while anti-dsDNA was 20% sensitive and 99% specific (J=0.39 vs 0.19; p<0.01). In the subset of subjects with high ANA and normal complement (117 SLE and 106 non SLE), abnormal CB-CAPs was 68% sensitive and 82% specific and yielded higher diagnostic value than anti-dsDNA (40% sensitive and 93% specific) (J=0.50 vs 0.34; p<0.01).

Conclusion: Abnormal CB-CAPs has higher diagnostic performances for SLE than low complement and anti-dsDNA and is a sensitive and specific measure for SLE in patients with high ANA titers and normal complement levels.

Disclosure: D. J. Wallace, Exagen, 2,Exagen, 5; E. Massarotti, Exagen, 2; R. Ramsey-Goldman, Exagen, 2; C. E. Collins, Exagen, 2,Exagen, 8; A. Askanase, Exagen, 2; J. P. Buyon, Exagen, 2; R. Furie, Exagen, 2; S. Narain, Exagen, 2; A. Saxena, Exagen, 2; K. C. Kalunian, Exagen, 2; C. Arriens, Exagen, 2; C. Putterman, Exagen, 2; J. Conklin, Exagen, 3; R. Alexander, Exagen, 3; C. Ibarra, Exagen Diagnostics, Inc., 3; T. O'Malley, Exagen Diagnostics, 3; T. Chandra, Exagen, 5; J. Ahearn, Exagen, 2,Exagen, 5,Exagen, 7; S. Manzi, Exagen, 2,Exagen, 7,Exagen, 5; A. Weinstein, Exagen, 2,Exagen, 5,Exagen, 9; T. Dervieux, Exagen, 3.

To cite this abstract in AMA style:

Wallace DJ, Massarotti E, Ramsey-Goldman R, Collins CE, Askanase A, Buyon JP, Furie R, Narain S, Saxena A, Kalunian KC, Arriens C, Putterman C, Conklin J, Alexander R, Ibarra C, O'Malley T, Chandra T, Ahearn J, Manzi S, Weinstein A, Dervieux T. Cell Bound Complement Activation Products Distinguish Systemic Lupus Erythematosus from Other Diseases Among Patients with High Antinuclear Antibody Titers and Normal Complement [abstract]. Arthritis Rheumatol. 2017; 69 (suppl 10). https://acrabstracts.org/abstract/cell-bound-complement-activation-products-distinguish-systemic-lupus-erythematosus-from-other-diseases-among-patients-with-high-antinuclear-antibody-titers-and-normal-complement/. Accessed .

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