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307 The pathogenic mechanisms of systemic lupus erythematosus associated genes pnp, plekhf2 and ankrd44
  1. J Qian and
  2. S Nan
  1. RenJi Hospital- School of Medicine- Shanghai JiaoTong University, Shanghai Institute of Rheumatology, Shanghai, China

Abstract

Background and aims To detect the expression of three SLE-susceptible genes, PNP, PLEKHF2 and ANKRD44 in SLE PBMC and lupus nephritis kidney samples, and to investigate their function.

Methods We collected PBMC from 46 SLE patients and 48 healthy controls, and renal biopsy tissues from 12 lupus nephritis patients and peri carcinomatous tissues from 10 patients with kidney cancer. The mRNA expression levels of PNP, PLEKHF2 and ANKRD44 were detected by qPCR. Their expression levels with the SLE clinical features and IFN scores were analysed. ANKRD44 was tested at different time points in Raw264.7 cells during IFN stimulation. The expression of ANKRD44 was knockdown by using siRNA in Raw264.7 cells. The change of IFIGs and the activation of IFN signalling pathway were detected by Real-time PCR and western blotting.

Results PNP, PLEKHF2 and ANKRD44 were found significantly decreased in SLE PBMCs compared with healthy controls. The mRNA expression of PNP and ANKRD44 were significantly decreased while the expression of PLEKHF2 was increased in kidney of lupus nephritis. The expression of PNP was negatively correlated with IFN score in SLE PBMC samples, while the expression of ANKRD44 was negatively correlated with IFN score in lupus nephritis kidney. ANKRD44, which could be down-regulated by IFN alpha, could inhibit the type I IFN signalling pathway and downregulate the expression of IFIGs.

Conclusions PNP and ANKRD44, expressed abnormally and associated with IFN alpha, might be used as new candidate biomarkers for SLE diagnosis; ANKRD44 could repress the IFN downstream pathway, it would be a potential drug target.

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