Measurement of cell-bound complement activation products enhances diagnostic performance in systemic lupus erythematosus

Authors

  • Kenneth C. Kalunian,

    1. University of California, San Diego, La Jolla
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    • Drs. Kalunian, Furie, Putterman, Ramsey-Goldman, Buyon, and Weinstein have received honoraria for serving on the Exagen Diagnostics advisory board (less than $10,000 each).

  • W. Winn Chatham,

    1. University of Alabama at Birmingham
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  • Elena M. Massarotti,

    1. Brigham and Women's Hospital, Boston, Massachusetts
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  • Joyce Reyes-Thomas,

    1. Albert Einstein College of Medicine and Montefiore Medical Center, Bronx, New York
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  • Cole Harris,

    1. Exagen Diagnostics, Vista, California
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    • Mr. Harris and Dr. Dervieux own stock or stock options in Exagen Diagnostics and are listed as named inventors on a patent held by Exagen Diagnostics for a diagnostic method for systemic lupus erythematosus.

  • Richard A. Furie,

    1. Hofstra North Shore–Long Island Jewish School of Medicine, Hempstead, New York
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    • Drs. Kalunian, Furie, Putterman, Ramsey-Goldman, Buyon, and Weinstein have received honoraria for serving on the Exagen Diagnostics advisory board (less than $10,000 each).

  • Puja Chitkara,

    1. San Diego Arthritis Medical Clinic, San Diego, California
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  • Chaim Putterman,

    1. Albert Einstein College of Medicine and Montefiore Medical Center, Bronx, New York
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    • Drs. Kalunian, Furie, Putterman, Ramsey-Goldman, Buyon, and Weinstein have received honoraria for serving on the Exagen Diagnostics advisory board (less than $10,000 each).

  • Rachel L. Gross,

    1. Albert Einstein College of Medicine and Montefiore Medical Center, Bronx, New York
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  • Emily C. Somers,

    1. University of Michigan, Ann Arbor
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  • Kyriakos A. Kirou,

    1. Hospital for Special Surgery, New York, New York
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  • Rosalind Ramsey-Goldman,

    1. Northwestern University Feinberg School of Medicine, Chicago, Illinois
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    • Drs. Kalunian, Furie, Putterman, Ramsey-Goldman, Buyon, and Weinstein have received honoraria for serving on the Exagen Diagnostics advisory board (less than $10,000 each).

  • Christine Hsieh,

    1. Northwestern University Feinberg School of Medicine, Chicago, Illinois
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  • Jill P. Buyon,

    1. New York University School of Medicine, New York, New York
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    • Drs. Kalunian, Furie, Putterman, Ramsey-Goldman, Buyon, and Weinstein have received honoraria for serving on the Exagen Diagnostics advisory board (less than $10,000 each).

  • Thierry Dervieux,

    Corresponding author
    1. Exagen Diagnostics, Vista, California
    • Exagen Diagnostics, Inc., 1261 Liberty Way, Vista, CA 92081
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    • Mr. Harris and Dr. Dervieux own stock or stock options in Exagen Diagnostics and are listed as named inventors on a patent held by Exagen Diagnostics for a diagnostic method for systemic lupus erythematosus.

  • Arthur Weinstein

    1. Washington Hospital Center, Washington, DC
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    • Drs. Kalunian, Furie, Putterman, Ramsey-Goldman, Buyon, and Weinstein have received honoraria for serving on the Exagen Diagnostics advisory board (less than $10,000 each).


Abstract

Objective

To determine the value of cell-bound complement activation products in combination with antinuclear antibody (ANA), anti–double-stranded DNA antibody (anti-dsDNA), and anti–mutated citrullinated vimentin antibody (anti-MCV) for the diagnosis of systemic lupus erythematosus (SLE).

Methods

This was a multicenter cross-sectional study in which 593 subjects were enrolled (210 SLE patients, 178 patients with other rheumatic diseases, and 205 healthy subjects). Complement receptor 1 levels on erythrocytes (ECR1) together with complement C4d levels on erythrocytes (EC4d), platelets (PC4d), and B cells (BC4d) were determined using fluorescence-activated cell sorting. Serologic markers were measured by enzyme-linked immunosorbent assay. Statistical analyses were performed using area under the curve (AUC), logistic regression, and calculations of diagnostic sensitivity and specificity.

Results

Anti-dsDNA was an insensitive (30%) but specific (>95%) marker for SLE. Levels of EC4d, BC4d, and PC4d were several times higher, and levels of ECR1 lower, in SLE patients compared to patients with other rheumatic diseases and healthy subjects. Among 523 anti-dsDNA–negative subjects, multivariate logistic regression analysis revealed that SLE was associated with ANA positivity (≥20 units), anti-MCV negativity (≤70 units), and elevated levels of both EC4d and BC4d (AUC 0.918, P < 0.001). A positive index score corresponding to the weighted sum of these 4 markers correctly categorized 72% of SLE patients. Specificity in relation to patients with other rheumatic diseases and healthy controls was >90%. The combination of anti-dsDNA and index score positivity yielded 80% sensitivity for SLE and 87% specificity against other rheumatic diseases.

Conclusion

An assay panel combining anti-dsDNA, ANA, anti-MCV, EC4d, and BC4d is sensitive and specific for the diagnosis of SLE.

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