Novel Lupus - Musik / Film / Buku dicari Riau. [PDF] novel Biological treatments for systemic lupus erythematosus by MD Shira Bezalel. PDF | Purpose of Review: The standard treatment options for systemic lupus erythematosus (SLE) are focused on non-specific. PDF | Objective: In order to investigate the pathogenesis role of proteins in systemic lupus erythematosus (SLE). Methods: Protein profiles of serum samples.

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Novel evidence‐based systemic lupus erythematosus responder index. Vibeke Strand. Arthritis & Rheumatism (Arthritis Care & Research) Vol. 61, No. AN ANALYSIS OF CODE MIXING USED IN THE NOVEL. LUPUS RETURNS: CEWEK JUNKIES. BY HILMAN WIJAYA. RESEARCH PAPER. Submitted as a. Lupus adalah tokoh fiksi dalam serial novel berjudul sama karangan Hilman Hariwijaya. Novel Lupus pertama diterbitkan pada tahun berjudul Lupus I.

In some cases, patients reported that it was difficult to distinguish side effects caused by steroids from symptoms of the disease, or other treatment side effects; this may limit the ability of the SSQ to accurately attribute burden to steroid use. Longitudinal use and analysis of individual changes to the SSQ over time may help to better differentiate between the effects of steroids themselves, and other factors.

In addition to assessing the benefits, side effects and other patient impacts of steroids, it is important to take into account the wider economic consequences of steroid therapy. Reducing the dose of steroids reduces the incidence of steroid-related AEs and therefore the economic burden of the therapy [ 14 ]. In addition, the sample captured the diversity of patients with SLE as it included both Caucasian and African American patients, as well as patients with a range of disease severity.

Of the 33 patients enrolled in the CE interviews, only one was male. Although the incidence of SLE is much lower among men than women, [ 16 ] the inclusion of more men in the study population would have been preferable. Patients participating in the CD interviews were all of moderate or mild severity. Patients with mild SLE felt that some items were not relevant to them because they had not experienced the benefit or side effect, thus, some items eg, having difficulty sleeping of the SSQ may only be relevant to patients with moderate or severe SLE.

Another potential limitation of this study was the length of the CD interviews. Not all questions could be asked of all patients; only a small number of patients reviewed each item, though interviews focused on items that were more challenging in terms of patient understanding. Further studies will be required to fully evaluate the SSQ in terms of its validity, reliability, sensitivity, and responsiveness to change over time including a preliminary determination of a responder definition before it can be used with confidence in clinical studies and real-world clinical practice.

Traditional psychometric testing and exploratory factor analysis, should be conducted in order that both item and scale scores can be used in the analysis of SSQ data.

Once adequate measurement properties of the SSQ are demonstrated, the SSQ may have many uses in both clinical studies and clinical practice.

The SSQ can be utilized in both cross-sectional and longitudinal studies. For example, within clinical studies the SSQ may assess the impact of steroids on specific SLE symptoms and impacts and to assess the steroid-sparing effect of a therapy. In the clinical practice setting, the baseline data provided by the SSQ could be used by physicians to assess the current burden of steroids on a patient. Although the SSQ was developed for use by patients with SLE, with modification and further validation, it could also be applicable to other patient populations in which steroid use is common, such as severe asthma or giant cell arteritis.

Conclusions In summary, the SSQ is a unique PRO measure designed to comprehensively assess the benefits, side effects, and other impacts of steroid treatment for patients. Following confirmation of its measurement properties, the SSQ may prove a useful tool in both clinical studies and clinical practice, to assess benefits and burdens associated with steroid use, and the steroid-sparing effect of therapies in SLE, with the potential for adaptation and use in other disease areas.

Availability of data and materials The dataset supporting the conclusions of this article is included within the article. All authors have contributed to the drafting of the manuscript, have given approval of the version and have agreed to be accountable for all aspects of the work. PB is a shareholder and employee of GSK.

KP was an employee of GSK at the time of the study. Consent for publication Ethics approval and consent to participate The study protocol was approved by the Copernicus Group, an independent review board.


All patients provided written, informed consent prior to their participation in the study. References 1.

Effect of corticosteroid use by dose on the risk of developing organ damage over time in systemic lupus erythematosus—the Hopkins Lupus Cohort. Lupus Sci Med.

The Dendritic Cell-T Cell Synapse as a Determinant of Autoimmune Pathogenesis

Accrual of organ damage over time in patients with systemic lupus erythematosus. J Rheum. PubMed Google Scholar 3.

Predictors of organ damage in systemic lupus erythematosus: the Hopkins lupus cohort. Arthritis Rheum. Increased production of human anti-dsDNA IgG could be detected significantly as early as four weeks post injection, and continued to increase to week 8 Supplementary Fig.

Lupus Nephritis and Pleuritis Lupus nephritis, or kidney inflammatory condition associated with SLE, affects the majority of SLE patients, and kidney failure is one of the leading causes of mortality in individuals with active SLE Lupus nephritis is characterised by the presence of immune deposits in the glomeruli, which induced leukocyte infiltration and severe damage, leading to protein leakage into the urine, or proteinuria Histological evaluation of kidneys from pristane-injected hu-mice revealed kidney inflammation and glomerular changes that are consistent with proliferative glomerulonephritis.

Novel therapeutic approaches in systemic lupus erythematosus.

Consistent with immune complex deposition observed in SLE patients, human IgG and IgM deposition was found in the glomeruli of pristane-injected hu-mice Fig. Expectedly, this was accompanied by increased proteinuria in pristane-injected humice, which was not observed in pristane-injected NSG Fig. The presence of kidney damage and proteinuria in pristane-injected hu-mice, but not pristane-injected NSG mice, again implicates the key role of human immune system, and the minimal contribution of residual mouse cells, in the induction of SLE pathogenesis upon pristane injection.

Figure 2 Lupus nephritis and pulmonary inflammation. The most common pulmonary manifestation associated with SLE is lung serositis inflammation in the lining of the lung, known as pleuritis and interstitial lung inflammation Pathological evaluation of lung from pristane-injected hu-mice revealed increased multifocal serosal and subpleural inflammation with fibrosis, as well as perivascular interstitial and intra-alveolar mononuclear cell infiltrate Fig.

Altogether, the presence of lupus nephritis, pulmonary serositis, and autoantibodies production showed that pristane injection could induce SLE pathogenesis that is mediated by the human immune system in hu-mice. Lymphopenia in pristane-injected hu-mice Lymphopenia is a common feature and one of the diagnostic criteria in SLE It, however, is not often recapitulated in most SLE animal models; instead, many well-studied SLE mouse models displayed massive lymphoproliferation 6.

Pristane injection into hu-mice induced a dramatic drop in the reconstitution percentage and absolute number of human immune cells in the blood over a period of 12 weeks Fig. Consistent with lymphopenia observed in SLE patients 25 , there was a significant reduction in the absolute number of human T cells, B cells and NK cells.

B cell numbers were significantly reduced as early as four weeks post pristane injection, while the number of T cells and NK cells were reduced at a later stage at week 8 and 10, respectively Fig.

Notably, pristane injection to hu-mice induced an accumulation of both human and mouse immune cells in the peritoneal lavage Supplementary Fig. S3B , and a mild spleen enlargement with a significant increase in the number of mouse, but not human immune cells Supplementary Fig.

Novel Insights in Systemic Lupus Erythematosus and Atherosclerosis

Figure 3 Lymphopenia in pristane-injected hu-mice. Full size image Lymphocyte hyperactivation in hu-mice As antibody producing cells, B cells have been the focus of many studies and targeted immunotherapies for SLE, not only for their role in producing autoantibodies, but also in antigen presentation and cytokine expression Various B cell anomalies have been reported in SLE patients, including lymphopenia, hyperactivation, relative expansion of memory B cells, as well as increased frequency of antibody-producing plasma cells To determine B cell abnormality in pristane-injected hu-mice, B cell subsets and activation markers in peripheral blood as well lymphoid organs were analysed by flow cytometry.

Indeed, pristane injection induced systemic B cell hyperactivation, as indicated by the increased expression of B cell activation marker CD86, in peripheral blood, spleen, mesenteric lymph nodes and peritoneal lavage Fig. There was increased frequency Fig. S4A and number Supplementary Fig. Figure 4 B cell hyperactivation and anomalies. B cells activation was measured by expression of B cell activation marker, CD Full size image In addition to its role in supporting antibodies production, T cells majorly contribute to the inflammatory response in SLE through inflammatory cytokine production and tissue infiltrations that often lead to organ damage Various signaling abnormalities in T cells lead to chronic T cell activation, reduced peripheral tolerance, and accumulation of autoreactive memory T cells Hence, we conclude that both T cell and B cell activation play a significant role in the pathogenesis of induced SLE in hu-mice.

Moreover, SLE induction in hu-mice exhibited lymphocyte anomalies with high resemblance to the anomalies observed in SLE patients. Figure 5 T cell hyperactivation and accumulation of memory cells. Full size image Production of human pro-inflammatory cytokines Both T cells and B cells contribute to SLE pathogenesis through aberrant cytokines production, which modulates the innate and adaptive immune responses To measure the involvement of human cytokines in pristane-induced SLE in hu-mice, human pro-inflammatory cytokine levels were measured in blood plasma as well as peritoneal lavage fluid.

Figure 6 Aberrant production of human pro-inflammatory cytokines. Ct: control; Pr: pristane. Taken together, systemic lymphocytes hyperactivation coupled with aberrant production of pro-inflammatory cytokines and increased expression of ISGs, suggests that pristane injection into hu-mice induces a chronic systemic inflammation similar as was seen in SLE. Discussion Hu-mice containing stable engraftment of human immune system in immunodeficient mouse have proven to be instrumental in the study of human immunology, particularly for human-specific infectious diseases and cancer models Nevertheless, hu-mice have not been widely used in the study of human autoimmune diseases, and previous attempts to model human SLE in humanised mice met with various limitations 17 , 18 , Despite its artificial nature of induction, pristane-induced SLE model strongly recapitulates many of the human SLE symptoms in mice.

Here we show that pristane injection into hu-mice could induce SLE pathogenesis that is mediated by human immune system, and recapitulate major clinical and immunological features found in SLE patients. Different hu-mice models could be generated from different sources of human HSCs engrafted to various immunodeficient mice strains. To date, NSG mice used in this study are among the best immunodeficient recipient strains for human cell engraftment: they have a long life span; completely devoid of mature lymphocytes and NK cells; and support stable development of human HSCs into mature and functional immune cells The lymphoid tissues were, as expected, largely devoid of mouse immune cells, and were mostly comprised of human immune cells Supplementary Fig.

Still, residual mouse myeloid cells remain present in NSG, and pristane injection notably induced increased number of mouse immune cells in the spleen and peritoneal lavage Supplementary Fig.

As such, we cannot completely rule out the contribution of the residual mouse myeloid cells in the induction and pathogenesis of SLE. Still, many approaches to completely eradicate these residual mouse cells are currently being generated, which would tremendously improve the application of hu-mice particularly in the studies of autoimmunity Production of anti-nuclear autoantibodies is one of the characteristic features of SLE.

In the current study, we could not assess the difference in disease severity between hu-mice derived from male and female HSC donors, which would require a much larger cohort of HSC donors. However, there was no significant difference in the level of anti-dsDNA production in male and female pristane-injected hu-mice Supplementary Fig.Telemedicine is a modality that has been useful to improve access to care, especially in rural areas.

In some cases, patients reported that it was difficult to distinguish side effects caused by steroids from symptoms of the disease, or other treatment side effects; this may limit the ability of the SSQ to accurately attribute burden to steroid use. Pristane injection into hu-mice induced a dramatic drop in the reconstitution percentage and absolute number of human immune cells in the blood over a period of 12 weeks Fig.

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A trial of contracep- izing anti-B-lymphocyte stimulator BLyS monoclonal tive methods in women with systemic lupus erythematosus.

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