Recent data published in Lupus Science & Medicine suggest that erythrocyte-bound C4d (EC4d) is associated with disease activity in systemic lupus erythematosus (SLE) and may be useful for monitoring SLE disease regardless of complement C3/C4 status.

Researchers sought to compare the performance of EC4d, low complement C3/C4, and autoantibodies to anti-double-stranded DNA (dsDNA) and complement C1q in tracking SLE disease activity. They collected data and blood samples from 3 studies that 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).

Clinical SELENA-SLEDAI scores were assessed without dsDNA and low complement C3/C4. The investigators determined EC4d levels using flow cytometry and evaluated dsDNA antibodies and C3 and C4 proteins.


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The study was comprised of a total of 124 patients with SLE (mean age, 42 years; 97% women) from the 3 studies. Participants were followed for an average of 5 consecutive visits, with a range of 2 to 13 visits. The results showed that EC4d levels and low complement C3/C4 status were significantly associated with clinical SELENA-SLEDAI or PGA scores in each of the 3 study cohorts (P <.05).

Furthermore, multivariate analysis showed that EC4d levels (slope estimate, 0.94±0.28) and low complement C3/C4 (slope estimate, 1.24±0.43) were independently and significantly associated with clinical SELENA-SLEDAI (P <.01) and PGA scores.

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EC4d levels were also associated with clinical SELENA-SLEDAI (slope estimate, 1.20±0.29) and PGA (slope estimate, 0.19±0.04) scores in patients with chronically low or normal complement C3/C4 (P <.01). The researchers noted that anti-dsDNA titers were generally associated with SLE disease activity.

“Our data expand initial work associating EC4d with SLE disease activity, and further support the usefulness of EC4d in the monitoring of SLE,” the authors concluded. “Moving forward, it will be important to further evaluate these laboratory measures as objective endpoints in interventional clinical trials and as aids to guide optimal treatment decisions when clinical disease activity assessment is not easily discerned.”

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Reference

Merrill JT, Petri MA, Buyon J, et al. Erythrocyte-bound C4d in combination with complement and autoantibody status for the monitoring of SLE [published online May 23, 2018].  Lupus Sci Med. doi:10.1136/lupus-2018-000263