The elevated serum levels of calcineurin and nuclear factor of activated T-cells 1 in children with Kawasaki disease

Zhimin Geng,Fangqi Gong,Fenglei Zheng,Ying Wang,Yiying Zhang,Songling Fu,Jingjing Liu,Yijing Tao,Yameng Sun,Chunhong Xie,Wei Wang

doi:10.1186/s12969-020-0420-8

Zhimin Geng, Fangqi Gong + Show 9 more

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https://doi.org/10.1186/s12969-020-0420-8

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Abstract

BackgroundThe calcineurin and nuclear factor of activated T-cells (CaN-NFAT) signaling pathway had been found to be associated with Kawasaki disease (KD) susceptibility and coronary artery aneurysm formation as a contributor. To evaluate serum calcineurin (CaN) and nuclear factor of activated T-cells 1(NFAT1) levels in patients with Kawasaki disease (KD).MethodsSerum levels of CaN and NFAT1 were measured by enzyme-linked immunosorbent assay method in 66 healthy children and 74 KD patients at acute, afebrile and subacute stage.ResultsThe serum levels of CaN and NFAT1 increased significantly in the acute stage, and decreased progressively in the afebrile and subacute stage, along with the reduction of C-reactive protein, white blood cells and neutrophil counts. And in the acute stage, the afebrile stage and the subacute stage, the expression of CaN and NFAT1 was upregulated significantly in KD patients compared to that in the healthy control. After the IVIG treatment, the serum levels of CaN and NFAT1 declined significantly in IVIG responders. However, the CaN and NTAT1 levels in the IVIG non-responders declined slowly. And in the afebrile stage, the NFAT1 levels were lower in KD patients with coronary artery lesions (CALs) (268.82 ± 11.96 ng/ml) than those without CALs (285.84 ± 25.13 ng/ml). However, the serum levels of CaN in KD patients with CALs had no significant difference with those in KD patients without CALs.ConclusionsThe specific regulation of CaN and NFAT1 serum levels in the course of KD was suggested that both of them were related in the development of KD.

Highlights

The calcineurin and nuclear factor of activated T-cells (CaN-NFAT) signaling pathway had been found to be associated with Kawasaki disease (KD) susceptibility and coronary artery aneurysm formation as a contributor
The calcineurin and nuclear factor of activated T-cells (CaN-NFAT) pathway was first identified in T cells, Sun et al Pediatric Rheumatology (2020) 18:23 where NFAT acts as a master regulator of lymphocyte proliferation, differentiation, and development [4, 5]
There were no significant differences in age and weight between KD patients and healthy control

Summary

Introduction

The calcineurin and nuclear factor of activated T-cells (CaN-NFAT) signaling pathway had been found to be associated with Kawasaki disease (KD) susceptibility and coronary artery aneurysm formation as a contributor. To evaluate serum calcineurin (CaN) and nuclear factor of activated T-cells 1(NFAT1) levels in patients with Kawasaki disease (KD). The elevated serum calcineurin levels has been found in the early onset of coronary artery disease and was associated with the polymorphism at the promoter region on PPP3R1(Protein Phosphatase 3, Regulatory Subunit B, Alpha) [6]. NFAT1(NFATp or NFATc2), one of the NFAT transcription factors family, was regulated by Ca2+-signaling pathway, with triggering a rapid rise of intracellular Ca2+, followed by the activation of phosphatase CaN, NFAT dephosphorylation which can be inhibited by the CaN inhibitors (CNIs) cyclosporin A and FK506, translocation into the nucleus and combination with specific DNA elements in the regulatory regions of target genes [4, 9]. The NFAT1 serum levels has been confirmed to increase significantly in RA patients when compared with control group [10]

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