作者机构：
[唐群; 朱伟; 刘春燕] Dept of Pathology, Hunan University of Chinese Medicine, Changsha, 410208, China;[杨胜辉] Dept of Preventive Medicine, Hunan University of Chinese Medicine, Changsha, 410208, China;[Zeng H.] Dept of Physiology, Hunan University of Chinese Medicine, Changsha, 410208, China
作者机构：
[Liu, Chunyu; Yuan, Ning] Cent South Univ, Xiangya Hosp 2, Dept Psychiat, Changsha, Hunan, Peoples R China.;[Liu, Chunyu; Yuan, Ning] Cent South Univ, Xiangya Hosp 2, Mental Hlth Inst, Changsha, Hunan, Peoples R China.;[Liu, Chunyu; Yuan, Ning] Cent South Univ, Natl Clin Res Ctr Mental Disorders, Changsha, Hunan, Peoples R China.;[Liu, Chunyu; Yuan, Ning] Cent South Univ, Natl Technol Inst Mental Disorders, Changsha, Hunan, Peoples R China.;[Liu, Chunyu; Yuan, Ning] Hunan Univ Chinese Med, Sch Clin Med, Hunan Prov Brain Hosp, Dept Psychiat, Changsha, Hunan, Peoples R China.
通讯机构：
[Liu, CY ] C;Cent South Univ, Xiangya Hosp 2, Dept Psychiat, Changsha, Hunan, Peoples R China.;Cent South Univ, Xiangya Hosp 2, Mental Hlth Inst, Changsha, Hunan, Peoples R China.;Cent South Univ, Natl Clin Res Ctr Mental Disorders, Changsha, Hunan, Peoples R China.;Cent South Univ, Natl Technol Inst Mental Disorders, Changsha, Hunan, Peoples R China.
摘要：
<jats:title>Abstract</jats:title><jats:p>Inflammation is a natural defence response of the immune system against environmental insult, stress and injury, but hyper- and hypo-inflammatory responses can trigger diseases. Accumulating evidence suggests that inflammation is involved in multiple psychiatric disorders. Using inflammation-related factors as biomarkers of psychiatric disorders requires the proof of reproducibility and specificity of the changes in different disorders, which remains to be established. We performed a cross-disorder study by systematically evaluating the meta-analysis results of inflammation-related factors in eight major psychiatric disorders, including schizophrenia (SCZ), bipolar disorder (BD), autism spectrum disorder (ASD), major depression disorder (MDD), post-trauma stress disorder (PTSD), sleeping disorder (SD), obsessive–compulsive disorder (OCD) and suicide. A total of 43 meta-analyses involving 704 publications on 44 inflammation-related factors were included in the study. We calculated the effect size and statistical power for every inflammation-related factor in each disorder. Our analyses showed that well-powered case–control studies provided more consistent results than underpowered studies when one factor was meta-analysed by different researchers. After removing underpowered studies, 30 of the 44 inflammation-related factors showed significant alterations in at least one disorder based on well-powered meta-analyses. Eleven of them changed in patients of more than two disorders when compared with the controls. A few inflammation-related factors showed unique changes in specific disorders (e.g., IL-4 increased in BD, decreased in suicide, but had no change in MDD, ASD, PTSD and SCZ). MDD had the largest number of changes while SD has the least. Clustering analysis showed that closely related disorders share similar patterns of inflammatory changes, as genome-wide genetic studies have found. According to the effect size obtained from the meta-analyses, 13 inflammation-related factors would need <50 cases and 50 controls to achieve 80% power to show significant differences (<jats:italic>p</jats:italic> < 0.0016) between patients and controls. Changes in different states of MDD, SCZ or BD were also observed in various comparisons. Studies comparing first-episode SCZ to controls may have more reproducible findings than those comparing pre- and post-treatment results. Longitudinal, system-wide studies of inflammation regulation that can differentiate trait- and state-specific changes will be needed to establish valuable biomarkers.</jats:p>
作者机构：
[朱伟; 唐群; 刘春燕] Dept of Pathology, Hunan University of Chinese Medicine, Changsha, 410208, China;[杨胜辉] Dept of Preventive Medicine, Hunan University of Chinese Medicine, Changsha, 410208, China;[Zeng H.] Dept of Physiology, Hunan University of Chinese Medicine, Changsha, 410208, China;[魏科] Dept of Microbiology, Hunan University of Chinese Medicine, Changsha, 410208, China
作者机构：
[Yi, Bin; Zhang, Shuang; Zhang, H; Zhang, Wei; Gui, Ming; Zhang, Hao; Sun, Jian] Cent S Univ, Xiangya Hosp 3, Dept Nephrol & Rheumatol, 138 Tongzipo Rd, Changsha 410013, Hunan, Peoples R China.;[Liu, Chunyan] Hunan Univ Chinese Med, Dept Pathol, Changsha 410208, Hunan, Peoples R China.;[Li, Yan Chun] Univ Chicago, Dept Med, Div Biol Sci, 5841 S Maryland Ave, Chicago, IL 60637 USA.
通讯机构：
[Zhang, H ] C;Cent S Univ, Xiangya Hosp 3, Dept Nephrol & Rheumatol, 138 Tongzipo Rd, Changsha 410013, Hunan, Peoples R China.
关键词：
Inflammation;Systemic lupus erythematosus;Vitamin D receptor
摘要：
OBJECTIVE: Systemic lupus erythematosus (SLE) is characterized by uncontrolled production of pro-inflammatory cytokines. Vitamin D receptor (VDR) has potent anti-inflammatory activities. The aim of this study was to examine the correlation between VDR expression and inflammation and disease activity in patients with SLE. METHODS: Ninety-five SLE patients were recruited and divided into two groups, active and inactive, according to their SLE disease activity index (SLEDAI)-2 K, and 40 healthy individuals served as controls. The expression of VDR and NF-kappaB p65 in peripheral blood mononuclear cells (PBMCs) was determined by quantitative RT-PCR and Western blotting. VDR expression was correlated with inflammatory and diseases parameters in SLE patients. VDR regulation was also studied in THP-1 and Jurkat cell lines. RESULTS: PBMC VDR expression was downregulated in SLE patients, especially in the active SLE group. VDR mRNA levels were negatively correlated with SLEDAI-2 K (r = - 0.348, P = 0.001), Systemic Lupus International Collaborating Clinics (SLICC) renal activity scores (r = - 0.346, P = 0.014), and proteinuria (r = - 0.309, P = 0.002) and positively associated with serum complement C3 levels (r = 0.316, P = 0.002). Multiple stepwise regression analysis indicated that PBMC VDR downregulation was an independent risk factor for SLEDAI-2 K. VDR levels were also negatively correlated with NF-kappaB p65 (r = - 0.339, P = 0.001), TNF-alpha (r = - 0.268, P = 0.009), and IL-6 (r = - 0.313, P = 0.002) levels. In monocyte and T lymphocyte cell lines, TNF-alpha suppressed VDR expression, whereas 1,25-dihydroxyvitamin D blocked TNF-alpha-induced VDR downregulation. CONCLUSION: PBMC VDR expression is inversely associated with disease activity and inflammation in SLE patients, and VDR downregulation is likely driven by inflammation.
