Presentation: SIGLEC1, a Biomarker for Type-I-Interferon, Monitors Disease Activity and IFN-suppressive Therapy in SLE (2007)

133 SIGLEC1, a Biomarker for Type-I-Interferon, Monitors Disease Activity and IFN-suppressive Therapy in SLE

OBJECTIVE: Type-I-Interferon (IFN) has a pivotal role in the pathogenesis of systemic lupus erythematosus (SLE) and is therefore discussed as potential therapeutic target. The aim of our study was to establish a feasible surrogate marker for Type-I-IFN to monitor disease activity and effectiveness of Type-I-IFN suppressive therapy in SLE patients.
METHODS: Highly purified monocytes were isolated from whole blood of 9 SLE patients and of 8 healthy controls. Their corresponding transcriptomes were analyzed by the Affymetrix genechip technology. SIGLEC1 has been identified within the IFN-induced gene signature and its expression was validated at the protein level by multicolor flow cytometry in whole blood of 52 SLE patients and 34 healthy controls.
RESULTS: Transcriptomes of peripheral monocytes from SLE patients revealed a prominent Type-I-IFN signature. 17 surface proteins were identified as potential biomarkers for monitoring Type-I-IFN-mediated immune responses by flow cytometry. SILGEC1 was the most striking candidate among them and was identified as strongly up-regulated specifically in inflammatory and resident monocyte subsets of SLE patients. Frequency of SILGEC1 expressing monocytes correlated with disease activity (SLEDAI) and inversely with complement levels of C3 and C4. High dose glucocorticoid treatment of active SLE patients resulted in a dramatic reduction of SIGLEC1 expression.CONCLUSION: Inflammatory and resident monocytes contribute to the Type-I-IFN signature that was already described for peripheral blood mononuclear cells of SLE patients. It is suggested that SIGLEC1 is sufficient to detect SLE patients with activation of Type-I-IFN system who could have a benefit of new therapeutic approaches targeting Type-I-IFN. Therapy of SLE-patients could be optimized by calibrating new interferon-suppressive or glucocorticoid therapy with SILGEC-1.

 R. Biesen, None; C. Demir, None; F. Barchudarowa, None; M. Steinbrich-Zoellner, None; M. Backhaus, None; J.R. Gruen, None; T. Haeupl, None; G. Burmester, None; A. Radbruch, None; F. Hiepe, None; A. Gruetzkau, None.