中医药治疗系统性红斑狼疮证型及用药规律演变研究

目的:基于文献整理探讨中医药治疗系统性红斑狼疮(Systemic lupus erythematosus,SLE)的证候分类及用药规律演变。方法:检索中国知网(CNKI)、维普中文科技期刊数据库、中国学术期刊数据库中中医药治疗SLE的相关文献,时间限定为从数据库建立至2018年7月。对证型及药物进行分类并统计分析。结果:纳入文献725篇,总结归纳高频证型11个,出现频次最高的五个证型分别为热毒炽盛证、脾肾两(阳)虚证、阴虚内热(火旺)证、肝肾两(阴)虚证、气阴两虚证,累计频率62.11%。1965-2018年间,阴虚内热(火旺)证呈明显增长趋势;热毒炽盛证、脾肾两(阳)虚证及气阴两虚证在1965-2010年间呈增长趋势,在2011-2018年间呈下降趋势;肝郁气滞(脾虚)证在1965-2018年间呈下降趋势;其余证型均呈动态波动。涉及组方1522个,药物309味,使用15910次,总使用频率最高的5味药分别为生地黄、牡丹皮、茯苓、黄芪、甘草,总累计频率16.42%。使用频率最高药类为清热药和补虚药;生地黄、牡丹皮等清热药的使用频率趋势与热毒炽盛证保持一致,不同年份高频用药大致相似,用药频率存在较小差异。结论:SLE在内以阴阳亏虚为主,在外与热毒侵袭相关,属于本虚标实,其发展与生态环境、社会环境、药物使用等紧密相关,治当以清热凉血、活血祛瘀、益气养阴,并结合个人体质及环境变化辨证治疗。     

基于生物标志物探索系统性红斑狼疮中医药治疗机制的研究进展

系统性红斑狼疮（SLE）是一种多器官受累的自身免疫性疾病,目前基于糖皮质激素和免疫抑制剂的治疗,仍然存在很多局限性和个体差异。近年来,越来越多的研究表明,联合中医药治疗SLE具有疗效好,不良反应低和安全性高等优点。但是,中医药治疗SLE的确切调节机制和作用环节尚不明确,本文从代谢组学、免疫细胞、淋巴细胞因子和细胞凋亡等,对中医药治疗SLE机制的研究进行综述,为利用现代化方法探索祖国传统医学治疗SLE的机制研究提供思路。     

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome – Evidence for an autoimmune disease

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a frequent and severe chronic disease drastically impairing life quality. The underlying pathomechanism is incompletely understood yet but there is convincing evidence that in at least a subset of patients ME/CFS has an autoimmune etiology. In this review, we will discuss current autoimmune aspects for ME/CFS. Immune dysregulation in ME/CFS has been frequently described including changes in cytokine profiles and immunoglobulin levels, T- and B-cell phenotype and a decrease of natural killer cell cytotoxicity. Moreover, autoantibodies against various antigens including neurotransmitter receptors have been recently identified in ME/CFS individuals by several groups. Consistently, clinical trials from Norway have shown that B-cell depletion with rituximab results in clinical benefits in about half of ME/CFS patients. Furthermore, recent studies have provided evidence for severe metabolic disturbances presumably mediated by serum autoantibodies in ME/CFS. Therefore, further efforts are required to delineate the role of autoantibodies in the onset and pathomechanisms of ME/CFS in order to better understand and properly treat this disease.     

High levels of soluble GPR56/ADGRG1 are associated with positive rheumatoid factor and elevated tumor necrosis factor in patients with rheumatoid arthritis

Background

GPR56/ADGRG1 is a member of the adhesion-class G protein-coupled receptor (aGPCR) family important in brain development, oncogenesis and tumor metastasis. Like other aGPCRs, GPR56 is cleaved at the GPCR proteolysis site (GPS) motif into an N-terminal fragment (NTF) and a C-terminal fragment (CTF). Existence of soluble GPR56 (sGPR56) has been shown in vitro, however the underlying mechanism and its pathophysiologic role remains undetermined.

HLA-C1 ligands are associated with increased susceptibility to systemic lupus erythematosus

Recently, the role of killer cell immunoglobulin-like receptor (KIR) in autoimmune diseases has received increasing attention. The present study was undertaken to determine the association of KIR genes and the human leukocytes antigen (HLA) ligands with Systemic Lupus Erythematosus (SLE) and accompanying oxidative stress. Presence or absence of 17 KIR and 5 HLA loci was performed using the polymerase chain reaction-sequence specific primer (PCR-SSP) method by case-control study. A total of 45 SLE patients, and 60 healthy controls, all of Sicilian descent, were enrolled. Plasma values of the anti-oxidant molecule Taurine were determined in all subjects by capillary electrophoresis UV detection. The carrier frequency of the KIR2DS2 gene was significantly increased in SLE patients compared to healthy controls (73.3 versus 45.0%; OR?=?3.36; 95% CI?=?1.46–7.74; p?=?.005) suggesting a role of KIR2DS2 gene in the susceptibility to disease. We also observed a strong positive association between the presence of HLA-C1 ligands group and the disease (82.2% in SLE patients versus 41.7% in controls; OR?=?6.47, 95% CI?=?2.58–16.26; p?<?.0001). Stepwise logistic regression analysis supported the effect of the HLA-C1 ligands in SLE patients (OR?=?7.06, 95% CI?=?0.07–2.19; p?=?.002), while the KIR genes were no longer significant. Interestingly, we found that SLE patients HLA-C1 positive showed significantly decreased plasma levels of antioxidant activity marker Taurine (69.38?±?28.49?μmol/L) compared to SLE patients HLA-C1 negative (108.37?±?86.09?μmol/L) (p?=?.03). In conclusion, HLA-C1 ligands group was significantly associated with an increased risk of SLE as well as an increased oxidative stress status overall in SLE patients.     

Short-lived plasmablasts and long-lived plasma cells contribute to chronic humoral autoimmunity in NZB/W mice

The current view holds that chronic autoimmune diseases are driven by the continuous activation of autoreactive B and T lymphocytes. However, despite the use of potent immunosuppressive drugs designed to interfere with this activation the production of autoantibodies often persists and contributes to progression of the immunopathology. In the present study, we analyzed the life span of (auto)antibody-secreting cells in the spleens of NZB x NZW F1 (NZB/W) mice, a murine model of systemic lupus erythematosus. The number of splenic ASCs increased in mice aged 1-5 mo and became stable thereafter. Less than 60% of the splenic (auto)antibody-secreting cells were short-lived plasmablasts, whereas 40% were nondividing, long-lived plasma cells with a half-life of >6 mo. In NZB/W mice and D42 Ig heavy chain knock-in mice, a fraction of DNA-specific plasma cells were also long-lived. Although antiproliferative immunosuppressive therapy depleted short-lived plasmablasts, long-lived plasma cells survived and continued to produce (auto)antibodies. Thus, long-lived, autoreactive plasma cells are a relevant target for researchers aiming to develop curative therapies for autoimmune diseases.     

Combined search for anti-beta2-glycoprotein I and anticardiolipin antibodies in antiphospholipid syndrome: contribution to diagnosis

In this study we sought to assess (1) the diagnostic value of a combined search for anti-beta(2)-glycoprotein (abeta(2)-GPIs) and anticardiolipin antibodies (aCLs) in primary (APS I) and secondary (APS II) antiphospholipid syndrome and (2) the influence of the beta(2)-GPI preparation in the ELISA's results. abeta(2)-GPI and aCL concentrations were assessed in 70 patients with APS and compared with those in 65 patients with systemic lupus erythematosus (SLE) without clinical features of APS. In APS patients (38 with APS I, 32 with APS II), the diagnosis had to have been made at least 3 years earlier; in subjects with SLE, the diagnosis had to have been made at least 5 years earlier. All serum samples were tested for abeta(2) -GPI with the use of an in-house ELISA with an abeta(2) -GPI preparation from human plasma. Samples negative for abeta(2) -GPI were controlled with 2 additional beta(2)-GPI preparations, 1 from human serum and 1 from bovine serum. In APS, abeta(2)-GPIs were more frequent than in SLE (76% and 15%, respectively; P <.0001), mainly with IgG isotype and with significantly higher levels than those found in SLE. The specificity for APS was 92% for IgG abeta(2)-GPIs and 68% for IgG aCLs. The highest association with APS was found for the combination of the 2 markers (odds ratio 29; 95% confidence interval 10-76; P <.0001). Among the APS patients, 6 were positive for aCL only and remained negative regardless of which beta 2 -GPI preparation was used; 1 patient was aCL-negative and only positive with human beta 2 -GPI. These data emphasize the heterogeneity of the APS immunologic profile and the diagnostic possibilities of both antibodies.