48 research outputs found
Investigating novel pathways in B cell mediated autoimmunity in the context of the disease juvenile dermatomyositis
No full textThe Inflammatory Idiopathic Myopathies (IIM) are a rare group of myopathic autoimmune diseases diagnosed in both adults and children. Patients present with proximal muscle weakness and Gottron’s papules. Immunohistochemical analysis of muscle tissue from these patients has identified immune cell infiltrate and the expression of pro-inflammatory cytokines however, little is known about the peripheral immunological profile in juvenile and adult patient groups. There are three aims: Firstly, to investigate mechanisms driving B cell lymphocytosis and define pathological features of B cells in the blood of Juvenile Dermatomyositis (JDM) patients. Secondly, to identify specific immune cell signatures and cytokine profiles for myositis disease subtypes and correlate this data with measurements of disease activity. Finally, to delineate a correlation between the up-regulated type I interferon signature and dysfunction of cholesterol homeostasis in immune cells. Using a combination of cell culture, flow cytometry, RNA-seq, q-PCR and ELISA techniques this study has assessed the immune cell signature, B cell biology and IFN related mechanisms in patients with IIM. The results identified that JDM patients with active disease have a significantly expanded immature B cell population which was correlated with a type I IFN signature. Activation through TLR7 and IFN- may drive the expansion of immature B cells in JDM and skew the cells towards a more pro-inflammatory phenotype. There are unique immune signatures in adult disease sub-types, one example was an expanded Th17 population seen in adult dermatomyositis (ADM). Lastly, IFN- stimulation of T and B cells does change the expression of some genes that are part of the Hallmark cholesterol homeostasis pathway. In conclusion, the work undertaken during my thesis provides further evidence that anti- IFN biologics could be efficacious in the treatment of JDM. Also, the need for further investigation for the use of IL-17A inhibitors in the treatment of IIM
B Cells as a Therapeutic Target in Paediatric Rheumatic Disease
No full textB cells carry out a central role in the pathogenesis of autoimmune disease. In addition to the production of autoantibodies, B cells can contribute to disease development by presenting autoantigens to autoreactive T cells and by secreting pro-inflammatory cytokines and chemokines which leads to the amplification of the inflammatory response. Targeting both the antibody-dependent and antibody-independent function of B cells in adult rheumatic disease has led to the advent of B cell targeted therapies in clinical practice. To date, whether B cell depletion could also be utilized for the treatment of pediatric disease is relatively under explored. In this review, we will discuss the role of B cells in the pathogenesis of the pediatric rheumatic diseases Juvenile Idiopathic Arthritis (JIA), Juvenile Systemic Lupus Erythematosus (JSLE) and Juvenile Dermatomyositis (JDM). We will also explore the rationale behind the use of B cell-targeted therapies in pediatric rheumatic disease by highlighting new case studies that points to their efficacy in JIA, JSLE, and JDM
Altruistic and antisocial behaviors in children: An examination from the self-regulation model
No full textAltruism is a complex phenomenon which has been the subject of much empirical investigation. The present study sought to explore altruistic behavior in children within the self-regulation model espoused by Kanfer and his colleagues. This model suggests that altruistic behavior is a function of: self- and situational-monitoring, prosocial goals, self-control, and self-evaluation/self-reinforcement abilities. Furthermore, Kanfer and Rehm posit that depressed mood should inhibit self-regulation abilities and therefore, impede altruism whereas Cialdini suggests that depressed mood facilitates helping to lessen depression.The current study tested the Self-regulation paradigm as well as the two competing theories regarding depressed mood in a sample of 8-11 year old, clinic-referred and non clinic-referred children. It was hypothesized that altruistic behaviors would be most frequent for children high in the self-regulation skills of self- and situational-monitoring, prosocial goal-setting, and self-control. Moreover, it was predicted that children would be most likely to donate points to help an absent child when the cues for helping are highly salient and when there is a low conflict for altruistic behavior. It was further hypothesized that children higher in antisocial behaviors (such as those seen in clinic-referred children) would have more self-regulation deficits, endorse greater antisocial goals, and donate less points. Finally, the effect of mood on self-regulation and altruism was explored to determine which of the two competing theories was supported.The results of the present study supported the conceptualization of altruistic and antisocial behaviors from a self-regulation paradigm. Children higher in acting-out behaviors displayed less altruism and less empathy. Furthermore, these children endorsed fewer prosocial goals and had lower levels of self-control. Salience of cues for helping was also highly predictive of altruism, although conflict level did not predict donations. Additionally, it was found that depressed mood inhibited self-regulation abilities as predicted by Kanfer and Rehm rather than facilitated these abilities as posited by Cialdini and his colleagues. The implications of these results were discussed with regard to the development of intervention strategies aimed at increasing prosocial behaviors in conduct-disordered, acting-out children.Made available in DSpace on 2011-05-07T12:30:42Z (GMT). No. of bitstreams: 2
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The Role of Immunometabolism in the Pathogenesis of Systemic Lupus Erythematosus
No full textSystemic lupus erythematosus (SLE) is a chronic autoimmune disorder in which pathogenic abnormalities within both the innate and adaptive immune response have been described. In order to activated, proliferate and maintain this immunological response a drastic upregulation in energy metabolism is required. Recently, a greater understanding of these changes in cellular bioenergetics have provided new insight into the links between immune response and the pathogenesis of a number of diseases, ranging from cancer to diabetes and multiple sclerosis. In this review, we highlight the latest understanding of the role of immunometabolism in SLE with particular focus on the role of abnormal mitochondrial function, lipid metabolism, and mTOR signaling in the immunological phenomenon observed in the SLE. We also consider what implications this has for future therapeutic options in the management of the disease in future
Altruistic and antisocial behaviors in children: An examination from the self-regulation model
No full textAltruism is a complex phenomenon which has been the subject of much empirical investigation. The present study sought to explore altruistic behavior in children within the self-regulation model espoused by Kanfer and his colleagues. This model suggests that altruistic behavior is a function of: self- and situational-monitoring, prosocial goals, self-control, and self-evaluation/self-reinforcement abilities. Furthermore, Kanfer and Rehm posit that depressed mood should inhibit self-regulation abilities and therefore, impede altruism whereas Cialdini suggests that depressed mood facilitates helping to lessen depression.The current study tested the Self-regulation paradigm as well as the two competing theories regarding depressed mood in a sample of 8-11 year old, clinic-referred and non clinic-referred children. It was hypothesized that altruistic behaviors would be most frequent for children high in the self-regulation skills of self- and situational-monitoring, prosocial goal-setting, and self-control. Moreover, it was predicted that children would be most likely to donate points to help an absent child when the cues for helping are highly salient and when there is a low conflict for altruistic behavior. It was further hypothesized that children higher in antisocial behaviors (such as those seen in clinic-referred children) would have more self-regulation deficits, endorse greater antisocial goals, and donate less points. Finally, the effect of mood on self-regulation and altruism was explored to determine which of the two competing theories was supported.The results of the present study supported the conceptualization of altruistic and antisocial behaviors from a self-regulation paradigm. Children higher in acting-out behaviors displayed less altruism and less empathy. Furthermore, these children endorsed fewer prosocial goals and had lower levels of self-control. Salience of cues for helping was also highly predictive of altruism, although conflict level did not predict donations. Additionally, it was found that depressed mood inhibited self-regulation abilities as predicted by Kanfer and Rehm rather than facilitated these abilities as posited by Cialdini and his colleagues. The implications of these results were discussed with regard to the development of intervention strategies aimed at increasing prosocial behaviors in conduct-disordered, acting-out children.U of I OnlyETDs are only available to UIUC Users without author permissio
P120 Unveiling CD4+ metabolic dysregulation in systemic lupus erythematosus: implications for targeting mitochondrial dysfunction
No full textRETRACTED: Maternal dazap2 Regulates Germ Granules by Counteracting Dynein in Zebrafish Primordial Germ Cells
No full textThis article has been retracted: please see Elsevier Policy on Article Withdrawal (http://www.elsevier.com/locate/withdrawalpolicy).This article has been retracted at the request of the authors.The first author, a graduate student, has admitted orally and in writing to fabrication of data that she contributed to this article in which we reported a maternal requirement for the scaffold protein Dazap2 (Mdazap2) in germ granule maintenance by a mechanism that is epistatic to Tdrd7 and that counteracts Dynein activity. Furthermore, we reported that Dazap2 binds to Bucky ball, an essential regulator of oocyte polarity and germ plasm assembly, and colocalizes with the germ plasm in oocytes and in primordial germ cells. Although the protein interactions, expression, and localization results are valid, the first author has admitted orally and in writing to fabrication of all “mutant data” in Figures 1H and 1J, Figure 2, Figure 3, Figure 4, and Figures S2 and S3. Because the data presented in those figures do not reflect the standards of quality that are expected in science, and in order to protect the integrity of science, our laboratories, and institutes, we are retracting the paper. All authors agree with retraction of the paper
Louis B. Mayer presents a Fred Niblo Production: 'Ambrose Applejohn's Adventure', adapted by Bess Meredyth from the stage play by Walter Hackett, Grand Palace St. Albans
No full textNo description availabl
Juvenile idiopathic inflammatory myositis: an update on pathophysiology and clinical care
No full textThe childhood-onset or juvenile idiopathic inflammatory myopathies (JIIMs) are a heterogenous group of rare and serious autoimmune diseases of children and young people that predominantly affect the muscles and skin but can also involve other organs, including the lungs, gut, joints, heart and central nervous system. Different myositis-specific autoantibodies have been identified that are associated with different muscle biopsy features, as well as with different clinical characteristics, prognoses and treatment responses. Thus, myositis-specific autoantibodies can be used to subset JIIMs into sub-phenotypes; some of these sub-phenotypes parallel disease seen in adults, whereas others are distinct from adult-onset idiopathic inflammatory myopathies. Although treatments and management have much improved over the past decade, evidence is still lacking for many of the current treatments and few validated prognostic biomarkers are available with which to predict response to treatment, comorbidities (such as calcinosis) or outcome. Emerging data on the pathogenesis of the JIIMs are leading to proposals for new trials and tools for monitoring disease.</p
