ObjectiveThis study is aimed at investigating the characteristics of the spontaneous brain activity in inactive patients with nonneuropsychiatric systemic lupus erythematosus (non-NPSLE). Methods Thirty-one female inactive patients with non-NPSLE and twenty healthy controls were examined by resting-state functional magnetic resonance imaging (RS-fMRI). Three amplitude methods including amplitude of low-frequency fluctuations (ALFF), fractional amplitude of low-frequency fluctuations (fALFF), and percent amplitude of fluctuation (PerAF) (with and without standardization) were applied to evaluate the spontaneous brain activity. The correlation was performed between low-frequency oscillations and clinical and neuropsychological factors in inactive patients with non-NPSLE. Results Compared to healthy controls, patients with non-NPSLE showed increased standardized ALFF (mALFF) in the left inferior temporal gyrus and left putamen, decreased PerAF in the right postcentral gyrus and bilateral precentral gyrus, and increased standardized PerAF (mPerAF) in the left putamen and decreased mPerAF in the right postcentral gyrus and bilateral precentral gyrus. By standardized fALFF (mfALFF), no significant brain regions were found between the two groups. Correlation analysis revealed significantly positive correlations between glucocorticoid dose and PerAF in the right precentral gyrus and mPerAF in the left putamen, and Complement 3 (C3) and mPerAF in the right postcentral gyrus. There was a significant negative correlation between C3 and mALFF in the left putamen. Conclusion Abnormal low-frequency oscillations in multiple brain regions were found in inactive patients with non-NPSLE, indicating that the alteration of mALFF, PerAF, and mPerAF in specific brain regions might be an imaging biomarker of brain dysfunction in inactive patients with non-NPSLE.
Our data suggest that IL-12 promotes disease development in AIDP and in contrast to previously inflammatory assumptions, TNF-alpha may play double roles in GBS. The anti-inflammatory role of TNF-alpha realized through TNFR2 in AMAN is possibly a therapeutic mechanism in the IVIg treatment of AMAN.
Lupus nephritis (LN) is one of the most severe manifestations of systemic lupus erythematosus (SLE). Our previous studies demonstrated increased serum and renal Interleukin (IL)-22 in LN patients and MRL/lpr mice. This study investigated the role of IL-22 and its mechanism in LN. Here, we found that IL-22 was mainly produced by type 3 innate lymphoid cells (ILC3) in kidney of MRL/lpr mice. The systemic illness and local renal lesion were significantly alleviated in IL-22 or IL-22R gene knockout (KO) mice (IL-22 KO or IL-22R KO MRL/lpr mice) than control mice (MRL/lpr mice). IL-22 KO or IL-22R KO MRL/lpr mice had significantly slighter infiltration of macrophage in kidney than MRL/lpr mice. Consistently, by RNA-Seq, the expression of (CC motif) ligand 2 (CCL2) and (CXC motif) ligand 10 (CXCL10) was decreased in kidney of KO mice compared with control mice. By immunoblotting, significantly increased levels of STAT3 phosphorylation were found in the kidney of control mice compared to KO mice. In vitro, primary kidney epithelial cells from control mouse stimulated with recombinant IL-22 (rIL-22) expressed higher levels of CCL2, CXCL10, and phosphorylated STAT3. At the same time, when primary kidney epithelial cells were treated with rIL-22, transwell assay demonstrated their supernatant recruited more macrophages. In human kidney epithelial cell line (HK2) cells, when treated with rIL-22, we observed similar results with primary mouse kidney epithelial cells. Moreover, when cells were stimulated with rIL-22 following pre-treatment with STAT3 pathway inhibitor, the expression of CCL2 and CXCL10 were significantly reversed. Our findings demonstrate that IL-22 binding to IL-22R in kidney epithelial cells activated the STAT3 signaling pathway, enhanced the chemokine secretion and then promoted macrophage infiltration to the kidney of MRL/lpr mice, thus aggravated LN in lupus-prone mice. These findings indicate that IL-22 may play a pathogenic role in LN and may provide a promising novel therapeutic target for LN.
Purpose In this study, we seek to investigate dynamic changes of brain activity in non-neuropsychiatric systemic lupus erythematosus (non-NPSLE) patients with inactive disease. Patients and Methods Thirty-one non-NPSLE patients with inactive disease and 20 matched healthy controls underwent the blood oxygenation level-dependent fMRI examination. Dynamic regional homogeneity (ReHo) and fractional amplitude of low-frequency fluctuations (fALFF) were used to analyze the brain activity in typical band (0.01–0.08 Hz), slow-4 (0.027–0.073 Hz) and slow-5 (0.01–0.027 Hz). Pearson’s correlation analysis was performed to correlate dynamic regional homogeneity (dReHo) and dynamic fractional amplitude of low-frequency fluctuations (dfALFF) values for clusters of voxels where significant group differences were found with clinical variables in non-NPSLE patients with inactive disease. Results In typical band, non-NPSLE patients showed increased dReHo in left middle occipital gyrus (MOG) compared to healthy controls. Meanwhile, patients showed decreased dfALFF in right superior frontal gyrus (SFG) and bilateral middle frontal gyrus (MFG) in typical band. In slow-4, increased dReHo in left MOG was found in non-NPSLE patients. In slow-5, non-NPSLE patients showed increased dReHo in left MOG, left calcarine fissure and surrounding cortex, right precentral gyrus (PreCG) and left postcentral gyrus (PoCG). Meanwhile, non-NPSLE patients showed decreased dfALFF in left SFG, right MFG, and right PreCG in slow-5. Moreover, the glucocorticoid dose showed significantly negative correlations with dReHo values in right PreCG in slow-5, left PoCG in slow-5, and left MOG in typical band. Conclusion dReHo and dfALFF abnormalities in different frequency bands may be the key characteristics in the pathogenesis mechanism of non-NPSLE.
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