89 - CD14 DOWN-MODULATION AS A BIOMARKER IN KAWASAKI DISEASE

BACKGROUND/

Aim: To investigate the pathophysiology of Kawasaki disease (KD) from immunological view and to identify biomarkers linked to innate immunity in KD, we analyze the surface expression of CD14, CD38 and CD62L on monocytes, along with a quantitative assessment of CD14 down-modulation. CD14 serves as a coreceptor of PRRs and binds to a broad spectrum of PAMPs and DAMPs, in concert with TLR1/TLR2, TLR2/TLR6, TLR4 and TLR9.7. The CD14-TLR-ligand complex is internalized, resulting in a decrease of CD14 expression on the monocyte surface and innate immune activation.

Methods: 85 patients with KD and 135 patients with infection or non-infectious diseases were enrolled for this investigation. Flow cytometry was used to analyze the surface expression of CD14, CD38 and CD62L on monocytes, along with a quantitative assessment of CD14 down-modulation. Oxidative stress levels were evaluated using derivatives of reactive oxygen metabolites (d-ROMs) and antioxydant capacity measured by a free free radical elective evaluation system.
RESULTS: During the acute phase of KD, we observed a prominent CD14 down-modulation on monocytes, Moreover, patients with KD showed a significantly higher CD14 down-modulation compared with infectious and non-infectious disease controls. The surface expression of CD14 on monocytes was restored concurrently with responses to intravenous immunoglobulin and infliximab treatment in KD. D-ROM levels in patients with KD were significantly elevated compared with patients with infection and non-infectious diseases.Follwing intravenous immunoglobulin treatment, oxydative stress levels decreased in patients with KD.

Conclusion: Monitoring CD14 down-modulation on monocytes in real-time is a valuable strategy for assessing treatment response, distinguishing KD relapse from concomitant infections and selecting second-line therapy after IVIG treatment in KD patients.