Background We previously described the SLE-key® RuleOut test1,2 to rule out the presence of systemic lupus erythematosus (SLE) with 94% sensitivity, 75% specificity, and 93% negative predictive value. We also reported that the SLE-key® signature appeared to be independent of disease activity or duration3 suggesting4 that that the SLE-key® signature might persist over time in the same subject.
Objectives Here we report that the SLE-key® signature remains stable over time in paired samples drawn from most individual subjects, regardless of disease activity.
Methods We determined the SLE-key® RuleOut scores for 113 paired serum samples submitted by clinics specializing in SLE. SLEDAI scores at the time of the blood draw ranged from 0 to 22. The mean SLEDAI difference within the pairs was 2.7±6.3. Samples were collected from subjects with a T1-T2 time difference that ranged from 0 to 11.5 years (mean =2±2.6 years).
Results The SLE-Key® RuleOut test identifies an SLE-specific signature based on a profile of autoantibodies to a combination of nucleic acids (complex ssDNA and a defined oligonucleotide) and protein biomarkers. Patients with an SLE-key® score of >0.18 are considered not ruled out for a diagnosis of SLE. In 84% of paired samples, patients' SLE-key® scores remained essentially the same (Figure 1, closed circles). The scores for these subjects were stable, persistent, and independent of SLEDAI score or time between sampling. Significant changes in the SLE-key® scores of 18/113 patient pairs (open circles) appear to be independent of time between blood draws and change in SLEDAI score. In 7 cases there was a change in Rule Out status of the patients. In 3 cases, both scores were close to the 0.18 threshold and the change was deemed not significant. In 4 cases, patients' status changed from RuledOut to Not Ruled Out, but with no correlation to change in SLEDAI score or time between sampling dates. Records of patients with changing SLE-key® scores are being studied to determine the reasons and the clinical implications of the change.
Conclusions The SLE-key® RuleOut test detects a serologic signature which remains stable between sampling dates and over a long period of time after diagnosis in 84% of subjects. Subjects who were ruled out at T1 were generally ruled out at T2. Patients not ruled out at T1 remained not ruled out at T2. The clinical implications of a changing SLE-key® RuleOut score in the remaining 16% of patients may be meaningful, and are currently being carefully investigated.
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Acknowledgements The authors wish to acknowledge the invaluable contributions of Cohen-Gindi O, Lerner M, Tarnapolski O, Blumenstein Y, Javaherian A, Pitts J, Barton M and Wong E and Innovative Medicines Initiative Joint Undertaking under grant agreement n° 115308 BIOVACSAFE.
Disclosure of Interest C. Putterman Consultant for: ImmunArray, M. Petri: None declared, R. Caricchio: None declared, P. Safer Employee of: ImmunArray, K. Jakobi Employee of: ImmunArray, R. Sorek Employee of: ImmunArray, I. Gluzman Employee of: ImmunArray, S. Wallace Employee of: ImmunArray, I. Cohen Shareholder of: ImmunArray, Consultant for: ImmunArray