Altered B lymphocyte homeostasis and functions in systemic sclerosis

Beyond the production of autoantibodies, B-cells are thought to play a role in systemic sclerosis (SSc) by secreting proinflammatory/profibrotic cytokines. B-cells are a heterogeneous population with different subsets distinguished by their phenotypes and cytokine production. Data about B-cell subsets, cytokine production and intracellular pathways leading to this production are scarce in SSc. The aim of our study was to describe B-cell homeostasis, activation, proliferation, cytokine production in B-cells and serum and B-cell intracellular signaling pathways in SSc. We hypothezided that B-cell homeostasis and cytokine production were altered in SSc and could be explained by serum cytokine as well as by intracellular signaling pathway abnormalities.Forty SSc patients and 20 healthy controls (HC) were prospectively included. B-cell subsets were determined by flow cytometry using CD19, CD21, CD24, CD38, CD27, IgM and IgD. CD25, CD80, CD95, HLA-DR were used to assess B-cell activation. Intracellular production of IL-10 and IL-6 were assessed by flow cytometry after TLR9 and CD40 stimulation. IL-6, IL-10, Ki67, Bcl2 mRNA were quantified in B-cells. Cytokine production was also assessed in sera and supernatants of B-cell culture, using a multiplex approach. Signaling pathways were studied through phosphorylation of mTOR, ERK, STAT3, STAT5 using a flow cytometry approach.We found that SSc patients exhibited an altered peripheral blood B-cell subset distribution, with decreased memory B-cells but increased proportion of naive and CD21^LoCD38^Lo B-cell subsets. We observed an increased expression of activation markers (CD80, CD95, HLA-DR) on some B-cell subsets, mainly the memory B-cells. Secretion of IL-6, BAFF and CXCL13 were increased in SSc sera. There was no correlation between the peripheral blood B-cell subsets and the serum concentrations of these cytokines. After stimulation, we observed a lower proportion of IL-10 and IL-6 producing B–cells in SSc. Finally, we observed a significant decrease of mTOR phosphorylation in SSc patient B-cells.In conclusion, we observed an altered B-cell homeostasis in SSc patients compared to HC. Memory B-cells were both decreased and activated in patients. IL-10 producing B-cells were decreased in SSc. This decrease was associated with an alteration of mTOR phosphorylation in B-cells. Conversely, there was no correlation between serum cytokine profile and B-cell homeostasis alterations.     

Brain diffusion tensor MRI in systematic lupus erythematosus: A systematic review

Diffusion tensor imaging (DTI) maps the brain's microstructure by measuring fractional anisotropy (FA) and mean diffusivity (MD). This systematic review describes brain diffusion tensor Magnetic resonance imaging (MRI) studies in systemic lupus erythematosus (SLE).The literature was reviewed following the PRISMA guidelines and using the terms “lupus”, “systemic lupus erythematosus”, “SLE”, “diffusion tensor imaging”, “DTI”, “white matter” (WM), “microstructural damage”, “tractography”, and “fractional anisotropy”; the search included articles published in English from January 2007 to April 2017. The subjects included in the study were selected according to the ACR criteria and included 195 SLE patients with neuropsychiatric manifestation (NPSLE), 299 without neuropsychiatric manifestation (non-NPSLE), and 423 healthy controls (HC). Most studies identified significantly reduced FA and increased MD values in several WM regions of both NPSLE and non-NPSLE patients compared to HC. Subclinical microstructural changes were observed in either regional areas or the entire brain in both the non-NPSLE and NPSLE groups.     

严重急性呼吸道综合征并发肾脏损害的临床分析

目的　分析严重急性呼吸道综合征 (SARS)并发肾脏损害的临床特点。方法　对 89例SARS住院患者的临床症状、体征、肾功能等进行观察。对其中 8例有肾损害、12例无肾损害及 15例健康对照者分别检测了血清IL - 1β、IL - 6、TNF -α水平。对 2例SARS死亡患者进行了肾脏病理检查。结果　 89例患者中 10例 (11.11%)并发肾损害。重症SARS伴肾损害者 8例 ,明显高于轻症 ,P <0 .0 1。出现肾损害的患者中有糖尿病和 /或高血压病史的患者 7例 ,明显高于无基础疾病者 ,P <0 .0 5。SARS患者无论有无肾损害 3种细胞因子水平均明显高于对照组 ,P <0 .0 1或P <0 .0 5。有肾损害组的细胞因子水平明显高于无肾损害组 ,P <0 .0 1或P <0 .0 5。肾脏病理学检查可见肾间质灶状炎性细胞浸润等非特异改变。结论　SARS并发肾损害与病情轻重显著相关 ,有慢性基础疾病者更容易出现肾损害 ,肾损害的发生可能是SARS所致系统性炎症反应综合征在肾脏的表现。     

Bicaudal D2 is a novel autoantibody target in systemic sclerosis that shares a key epitope with CENP-A but has a distinct clinical phenotype

We studied the clinical correlations and epitopes of autoantibodies directed to a novel autoantigen, Bicaudal D (BICD2), in systemic sclerosis (SSc) and reviewed its relationship to centromere protein A (CENP-A). 451 SSc sera were tested for anti-BICD2 using a paramagnetic bead immunoassay and then univariate and multivariate logistic regression was used to study the association between anti-BICD2 and demographic and clinical parameters as well as other SSc-related autoantibodies. Epitope mapping was performed on solid phase matrices. 25.7% (116/451) SSc sera were anti-BICD2 positive, of which 19.0% had single specificity anti-BICD2 and 81.0% had other autoantibodies, notably anti-CENP (83/94; 88.3%). Compared to anti-BICD2 negative subjects (335/451), single specificity anti-BICD2 subjects were more likely to have an inflammatory myopathy (IM; 31.8% vs. 9.6%, p = .004) and interstitial lung disease (ILD; 52.4% vs. 29.0%, p = .024). Epitope mapping revealed a serine- and proline-rich nonapeptide SPSPGSSLP comprising amino acids 606–614 of BICD2, shared with CENP-A but not CENP-B. We observed that autoantibodies to BICD2 represent a new biomarker as they were detected in patients without other SSc-specific autoantibodies and were the second most common autoantibody identified in this SSc cohort. Our data indicate that the major cross-reactive epitope is associated with anti-CENP-A but, unlike anti-CENP, single specificity anti-BICD2 antibodies associate with ILD and IM.     

系统性红斑狼疮患者血清可溶性细胞间粘附分子-1、L-选择素、细胞因子的变化及意义

目的探讨系统性红斑狼疮（SLE）患者血清可溶性细胞间粘附分子-1（sICAM-1）、L-选择素、白细胞介素（IL）-2、IL-6、IL-8和IL-10水平的变化及其致病意义。方法采自24例SLE患者的血清标本分别用酶联免疫吸附试验（ELISA）检测sICAM-1和L-选择素;用放射免疫检测法（RIA）检测IL-2、IL-6、IL-8和IL-10;另以20名健康志愿者作为对照。结果SLE患者血清sICAM-1、L-选择素、IL-6及IL-2/IL-10比值显著高于对照组（P〈0.05）,IL-2无明显变化,IL-8水平稍高于对照组,但差异无统计学意义（P〉0.05）。结论SLE患者sICAM-1、L-选择素和IL-6表达增加,而IL-10表达减少,提示免疫紊乱、促炎与抗炎细胞因子失平衡参与了SLE的发病过程。     

系统性红斑狼疮病人的心理分析及护理对策

[目的]了解系统性红斑狼疮病人心身状态及其影响因素,并探讨其相应的护理对策。[方法]采用症状自评量表(SCL-90)对l17例系统性红斑狼疮病人的心身状态进行调查,所得结果进行统计学分析。[结果]系统性红斑狼疮病人SCL-90的9个因子分值均高于国内常模(P<0.01)。[结论]重视疾病知识的健康教育和行为疗法的指导,充分调动病人的主观积极性,才能有效地减轻或消除病人的心身痛苦,提高病人的生活质量。     

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.     

Intravenous Immunoglobulins as a new opportunity to treat discoid lupus erythematosus: A case report and review of the literature

Discoid lupus erythematosus (DLE) is a chronic dermatological disease that can lead to scarring, alopecia and dyspigmentation, if not properly treated. Actually, no drugs are specifically approved for the treatment of CLE, although the first-line therapy usually consists of photoprotection associated to topical or oral steroids, topical calcineurin inhibitors and hydroxychloroquine (HCQ). In cases of DLE refractory to these medications, many other agents have been employed, such as dapsone, methotrexate, azathioprine, cyclophosphamide, biologic drugs and Intravenous Immunoglobulin (IVIG).We described the case of a DLE patient resistant to combination therapy with steroid and HCQ who was successfully treated with cyclical IVIG therapy. The treatment with IVIG resulted rapidly effective with persistent efficacy and low rates of relapses, although more cycles of IVIG are needed to achieve a stable clinical remission.We also discussed the beneficial and promising effects of IVIG in patients with Cutaneous Lupus reporting the previously published data.     

Subclinical cardiovascular disease and Systemic Sclerosis: A comparison between risk charts,quantification of coronary calcium and carotid ultrasonography

Background and objectives

Recently published population-based cohort studies have shown a high prevalence of cardiovascular disease in Systemic Sclerosis (SSc) patients. The aim of this study is to compare three different methods to measure cardiovascular risk in patients with scleroderma.

Impact of micronutrient deficiency & malnutrition in systemic sclerosis: Cohort study and literature review

Objectives

The purpose of our study was to determine the prevalence and risk factors associated with malnutrition, and selenium (Se) and vitamin C (vitC) deficiencies in systemic sclerosis (SSc) patients.