The SLE-key test serological signature: new insights into the course of lupus

Objective. We previously described the multiplex autoantibody SLE-key Rule-Out test, which detects a signature of autoantibody reactivity that distinguishes healthy subjects from SLE patients with 94% sensitivity, 75% specificity and 93% negative predictive value; thus, an individual manifesting a positive Rule-Out test score is unlikely to have SLE (e.g. lupus is excluded). The objective of this current study was to evaluate the stability of the lupus-associated signature over time. Methods. We used banked serum samples from healthy subjects (n = 51) and lupus patients (n = 50 individual samples and n = 181 paired samples, for a total of n = 412 serum samples). The samples were drawn at different times after diagnosis to analyse the impact on the SLE-key Rule-Out test of time elapsed since diagnosis and any changes in disease activity (as reflected by the SLEDAI score). Results. The SLE signature remains stable for the first 10 years after diagnosis; in this time frame, < 10% of patients manifested a positive Rule-Out score and the SLE-key Rule-Out score was independent of the underlying disease activity as reflected by the SLEDAI score. After 510 years, similar to 30% of lupus subjects scored as SLE Ruled-Out; the proportion of patients manifesting this status was even greater in the subset of individuals with a SLEDAI score of 0. Conclusion. These findings raise the possibility that a significant number of SLE patients manifest a change in their serological signature over time, and that such a signature change may signify an evolution in the immunological features of their disease relevant to patient management.