Background Monitoring disease activity of patients with systemic lupus erythematosus (SLE) is essential in treatment decision-making, but is challenging due to the scarcity of sensitive biomarkers. The aim of this study was to investigate new biomarkers to monitor disease activity in SLE.
Methods The study included 34 SLE patients attending Hokkaido University Hospital from 2020 to 2021 and 15 healthy controls (HC). Clinical and laboratory data, including SLE Disease Activity Index (SLEDAI), were recorded. Serum samples were collected and inflammation-associated proteins were measured by Olink Explore 384 Inflammation panel using proximity extension assay technology. Peripheral blood mononuclear cells were also isolated and the proportion of peripheral immune cell types was evaluated by flow cytometry. The correlation between protein expression, SLEDAI, and the proportion of the immune cells were analyzed.
Results Of 34 patients, 31 were females, median age 40 years old and median SLEDAI 6.0. In serum samples, 368 inflammation-associated proteins were detected. Eighty-two proteins showed significant differences between SLE patients and HC, including 14 positive (r>0.4) and 4 negative (r<-0.4) correlations with SLEDAI. Cytoskeleton-associated protein 4 (CKAP4) exhibited the highest positive correlation with SLEDAI (r=0.54) and we focused on this protein. CKAP4 induces NF-κB pathway through transduction of Dickkopf-1 signal. Serum CKAP4 levels were higher even in SLE patients with low disease activity (SLEDAI≤4) than in HC (p<0.01). Moreover, in SLE patients, serum CKAP4 levels correlated with the population of Tph17 (r=0.68), Tfh17 (r=0.59), activated CD4 (r=0.68) and activated CD8 (r=0.51) T cells, which were increased in SLE patients compared with HC. Cytokine analysis showed correlations between serum levels of CKAP4 and those of TNFα (r=0.81), IL-6 (r=0.77) and IFNγ (r=0.67).
Conclusions Serum CKAP4 levels were upregulated in SLE and positively correlated with SLEDAI. Serum CKAP4 could be a potential novel biomarker in SLE.
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