Evaluation of SIGLEC1 in the diagnosis of suspected systemic lupus erythematosus

Zorn-Pauly, L.; von Stuckrad, A. S. L.; Klotsche, J.; Rose, T.; Kallinich, T.; Enghard, P.; Ostendorf, L.; Burns, M.; Doerner, T.; Meisel, C.; Schneider, U.; Unterwalder, N.; Burmester, G.; Hiepe, F.; Alexander, T.; Biesen, R.

Objectives: To evaluate and compare the diagnostic accuracy utility of SIGLEC1, a surrogate marker of type I IFN, compared to with established biomarkers in an inception cohort of systemic lupus erythematosus (SLE). Methods: SIGLEC1 was analysed by flow cytometry in our central laboratory facility in 232 patients referred to our institution with suspected SLE between October 2015 and September 2020. Results: SLE was confirmed in 76 of 232 patients (32.8%) according to the 2019 EULAR/ACR classification criteria and their . SIGLEC1 values were significantly higher in patients with SLE compared to patients without SLE (p<0.0001). A sensitivity of 98.7 %, a specificity of 82.1 %, a negative predictive value (NPV) of 99.2 % and a positive predictive value (PPV) of 72.8 % were calculated for SIGLEC1. Adjusted to the highest reported prevalence of SLE, the NPV and PPV were > 99.9 % and 0.1 %, respectively. Using ROC analysis and DeLlong testing, the area under the curve (AUC) for SIGLEC1 (AUC=0.95) was significantly higher than for ANA (AUC=0.88, p=0.031), C3 (AUC=0.83, p=0.001) and C4 (AUC=0.83, p=0.002) but not for anti-dsDNA antibodies (AUC=0.90, p=0.163). Conclusion: IFN-I pathway activation is detectable in almost most all newly diagnosed SLE patients, where SIGLEC1 outcompetes the performance of other biomarkers to exclude SLE with high predictability in suspected cases. Thus, a negative test result for SIGLEC1 is powerful to exclude SLE in suspected cases.