C4d levels predict lupus nephritis flares, help inform treatment
The complement activation product C4d can be used to monitor patients with systemic lupus erythematosus, as these levels correlate with disease activity and could potentially predict lupus nephritis flares, according to findings published in Arthritis Research and Care.
“Low serum levels of complement components C3 and C4 have been used for over 50 years to indicate lupus activity and are included in the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI),” Myriam Martin, PhD, of Lund University, in Malmö, Sweden, and colleagues wrote. “A variety of other biomarkers are used to diagnose [systemic lupus erythematosus (SLE)], to monitor disease activity and to identify and/or predict specific organ involvement. However, no biomarker covers all aspects of the different phenotypes of the disease, and some assays are prone to producing false-positive data owing to mistreatment of the samples.”
To study C4d, the final cleavage product of C4 that arises during complement activation, as a potential marker for lupus nephritis, the researchers recruited patients from the Lund University Department of Rheumatology. A cross-sectional cohort group included 98 patients with SLE who had plasma samples taken at lower or higher respective disease activity. A longitudinal study group included 69 patients with SLE that the researchers followed for up to 5 years. In addition, the researchers collected plasma samples from 77 healthy donors as a control group.
The researchers analyzed C4d levels through an enzyme-linked immunosorbent assay in plasma samples of patients with established SLE. To accomplish this, they used a novel approach based on detection of a short linear cleavage neoepitope, they wrote.
According to the researchers, C4d levels were scant among the healthy donors, but significantly increased in patients enrolled in the cross-sectional study (P < .0001).
Presence of C4d demonstrated a positive predictive value of 68% and discriminated between higher and lower SLE activity according to ROC curve analysis (P < .001). C4d levels, at high SLE disease activity, correlated with the modified SLEDAI (P = .011), demonstrating a sensitivity of 79% in identifying patients with lupus nephritis.
In the longitudinal study, high C4d levels, together with the presence of anti-dsDNA autoantibodies, predicted impending lupus nephritis (OR = 5.4; 95% CI, 1.4-21.3). When analyzing only the 19 patients with renal involvement, the researchers further determined that high C4d levels alone could predict the recurrence of future lupus nephritis (OR = 3.3; 95% CI, 1.2-9.6).
“Measuring C4d levels using our robust and practical assay provides a novel method of monitoring SLE activity that is at least as good as C3 and superior to C4 in identifying active disease and in particular [lupus nephritis],” Martin and colleagues wrote. “Most importantly, C4d levels are more valuable than either C3 or C4 in predicting recurrence of renal flares, aiding clinicians in adjusting treatment in time.” – by Jason Laday
Disclosure: Martin reports no relevant financial disclosures. See the full study for additional authors’ disclosures.