Evaluation of SIGLEC1 in the diagnosis of suspected systemic lupus erythematosus

ObjectivesTo evaluate and compare the diagnostic accuracy of SIGLEC1, a surrogate marker of type I IFN, with established biomarkers in an inception cohort of systemic lupus erythematosus (SLE). MethodsSIGLEC1 was analysed by flow cytometry in 232 patients referred to our institution with suspected SLE between October 2015 and September 2020. ResultsSLE was confirmed in 76 of 232 patients (32.8%) according to the 2019 EULAR/ACR classification criteria and their SIGLEC1 values were significantly higher 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 Delong 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). ConclusionIFN-I pathway activation is detectable in almost all newly diagnosed SLE patients. Thus, a negative test result for SIGLEC1 is powerful to exclude SLE in suspected cases.