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Erythrocyte-bound C4d in combination with complement and autoantibody status for the monitoring of SLE
  1. Joan T Merrill1,
  2. Michelle A Petri2,
  3. Jill Buyon3,
  4. Rosalind Ramsey-Goldman4,
  5. Kenneth Kalunian5,
  6. Chaim Putterman6,
  7. John Conklin7,
  8. Richard A Furie8 and
  9. Thierry Dervieux7
  1. 1 Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma, USA
  2. 2 Division of Rheumatology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
  3. 3 New York University School of Medicine, New York City, New York, USA
  4. 4 Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA
  5. 5 University of California San Diego School of Medicine, La Jolla, California, USA
  6. 6 Albert Einstein College of Medicine, Bronx, New York, USA
  7. 7 Exagen Diagnostics, Vista, California, USA
  8. 8 Northwell Health, Great Neck, New York, USA
  1. Correspondence to Dr Thierry Dervieux; tdervieux{at}exagen.com

Abstract

Background We examined the usefulness of erythrocyte-bound C4d (EC4d) to monitor disease activity in SLE.

Methods Data and blood samples were collected from three different studies, each of which included longitudinal evaluations using the Physicians Global Assessment (PGA) of disease activity and the Safety of Estrogens in Lupus Erythematosus National Assessment (SELENA) SLE Disease Activity Index (SLEDAI), which was assessed without anti-double-stranded DNA (dsDNA) and low complement C3/C4 (clinical SELENA-SLEDAI). EC4d levels were determined using flow cytometry; other laboratory measures included antibodies to dsDNA, C3 and C4 proteins. Relationships between clinical SELENA-SLEDAI, PGA and the laboratory measures were analysed using linear mixed effect models.

Results The three studies combined enrolled 124 patients with SLE (mean age 42 years, 97% women, 31% Caucasians and 34% African-Americans) followed for an average of 5 consecutive visits (range 2–13 visits). EC4d levels and low C3/C4 status were significantly associated the clinical SELENA-SLEDAI or PGA in each of the three study groups (p<0.05). Multivariate analysis revealed that EC4d levels (estimate=0.94±0.28) and low complement C3/C4 (estimate=1.24±0.43) were both independently and significantly associated with the clinical SELENA-SLEDAI (p<0.01) and PGA. EC4d levels were also associated with the clinical SELENA-SLEDAI (estimate: 1.20±0.29) and PGA (estimate=0.19±0.04) among patients with chronically low or normal C3/C4 (p<0.01). Anti-dsDNA titres were generally associated with disease activity.

Conclusion These data support the association of EC4d with disease activity regardless of complement C3/C4 status and its usefulness in monitoring SLE disease. Additional studies will be required to support these validation data.

  • complement
  • disease activity
  • systemic lupus erythematosus

This is an Open Access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/

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Footnotes

  • Contributors All authors participated in the collection of data and data interpretation. TD wrote the first draft of the manuscript. All authors contributed to and approved the final manuscript.

  • Funding This study was funded by Exagen Diagnostics. The Hopkins Lupus cohort is supported by National Institutes of Health grants R01 AR43727 and AR69572.

  • Competing interests JTM, MAP, JB, RR-G, KK, RAF and CP have received research grants from Exagen. TD and JC are employed by Exagen Diagnostics.

  • Patient consent Obtained.

  • Ethics approval Internal review boards approved the study.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data sharing statement None.

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