Publications by authors named "Ann K Lefvert"

Background: Dendritic cells (DCs) initiate immune responses through their direct interaction with effector cells. However, the mechanism by which DC activity is regulated is not well defined. Previous studies have shown that CTLA4 on T cells regulates DCs function by "cross-talk".

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Objective: Measurement of inflammatory mediators is an important tool to assess inflammation. We have, therefore, conducted a survey within the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) study to evaluate the inter-relationship between soluble CTLA-4 (sCTLA-4) and other inflammatory markers.

Materials And Methods: This is a population-based study, designed to quantify the circulating serum levels of sCTLA-4 and other inflammatory markers such as CRP and pro-inflammatory cytokines and chemokines by in-house ELISA, Immuno-turbidimetry and multiplex ELISA, respectively.

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  • The study investigates the genetic link between the PDCD1 gene and Wegener's granulomatosis (WG), a type of autoimmune disorder.
  • The researchers analyzed three specific SNPs in the PDCD1 gene among patients with WG and healthy controls, using methods like genotyping and ELISA.
  • Ultimately, they found no significant association of the PDCD1 SNPs with WG, indicating that these genetic factors may not play a role in the disease.
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  • Myasthenia gravis (MG) is an autoimmune disorder that causes muscle weakness due to autoantibodies targeting acetylcholine receptors, and CTLA-4 is implicated in its immune response.
  • Researchers identified two new isoforms of CTLA-4 mRNA through alternative splicing in peripheral blood mononuclear cells (PBMCs) from MG patients.
  • The study found reduced levels of soluble CTLA-4 mRNA in MG patients compared to healthy individuals, suggesting a unique mRNA expression pattern that warrants further investigation into how alternative splicing affects the disease.
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  • A study was conducted to explore the role of the PTPN22 R620W gene variant in myasthenia gravis (MG), involving 409 MG patients and 1557 controls from Sweden.
  • The W620 variant was found to be significantly more common in MG patients, with an odds ratio of 1.52, indicating a potential link to the disease.
  • Further tests on patient-derived cells showed that W620 carriers had increased production of anti-AChR antibodies and IL-2 when exposed to acetylcholine receptors, suggesting that this variant may impair immune function in the context of MG.
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  • An investigation into the role of the inhibitory receptor Programmed Death-1 (PD-1) in 273 patients with autoimmune myasthenia gravis revealed no significant genetic association with the disease through SNP genotyping.
  • Gene expression levels in patients did not differ from those in healthy controls.
  • However, there were higher levels of PD-1 on T cells and its ligand PD-L1 on monocytes in patients, indicating a potential natural regulatory role for PD-1 in myasthenia gravis.
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Certain alleles of cytokine genes interleukin-1 beta (IL-1beta), interleukin-1 receptor antagonist (IL-1Ra), and tumor necrosis factor alpha (TNF-alpha) are correlated with increased production of the proteins. The aim of this study was to investigate polymorphisms of these genes and their possible correlation with the development of stroke. This matched case-control study was nested within the population-based Västerbotten Intervention Program (VIP) cohort and the Northern Sweden World Health Organization MONICA (Multinational Monitoring of Trends and Determinants in Cardiovascular Diseases) cohort, based on individuals who were free from cardiovascular events when the cohorts were established.

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The costimulatory factors CD28, CD80, CD86 and CD152 needed to start and turn off an immune response are present as membrane receptors and soluble proteins. There was no difference in the serum levels of soluble costimulatory molecules in 153 healthy controls and 118 patients with myasthenia gravis. However, we could confirm that the soluble forms of ICAM-1 and CD25 were increased in patients.

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Inhibitory regulatory functions of B7-H3 and B7-H4 regarding T-cell activation have been reported recently. Little is known about the significance of human B7-H3 and B7-H4 expression in non-small-cell lung cancer (NSCLC), and we conducted the present study to address this issue in cell lines and tumor tissue from 70 patients. B7-H3 is over-expressed by all six NSCLC cell lines on both mRNA and protein level.

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Previously, we identified that a majority of patients with anorexia nervosa (AN) and bulimia nervosa (BN) as well as some control subjects display autoantibodies (autoAbs) reacting with alpha-melanocyte-stimulating hormone (alpha-MSH) or adrenocorticotropic hormone, melanocortin peptides involved in appetite control and the stress response. In this work, we studied the relevance of such autoAbs to AN and BN. In addition to previously identified neuropeptide autoAbs, the current study revealed the presence of autoAbs reacting with oxytocin (OT) or vasopressin (VP) in both patients and controls.

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Dendritic cells (DC), as initiators and orchestrators of immune responses, control both naive and primed T cell responses. Depending on their maturation stage, DC promote immunity or tolerance. Here we investigated (1) the phenotype and cytokine secretion patterns of IL-10-modulated immature DC (IL-10-DC) and lipopolysaccharide (LPS)-driven mature DC (LPS-DC) in comparison with unmodulated immature DC (imDC) and (2) the effects of IL-10-DC, and of LPS-DC, vs.

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Cytolytic T lymphocyte-associated antigen-4 (CTLA-4) plays a critical role in the down-regulation of antigen-activated immune responses. The aberrant CTLA-4 expression is characterized by low surface and intracellular levels of CTLA-4 protein, impaired up-regulation of CTLA-4 in T cells in response to ConA stimulation and high levels of soluble CTLA-4 (sCTLA-4) in serum. The serum levels of sCTLA-4 are positively correlated with the serum concentration of antibodies against the acetylcholine receptor.

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Article Synopsis
  • The study investigates the link between Wegener's granulomatosis (WG) and two specific single nucleotide polymorphisms (SNPs).
  • Findings show that patients with WG are more likely to be heterozygous for a C/T SNP in the promoter region, while homozygosity for C is less frequent compared to healthy controls.
  • The research concludes that the promoter SNP is associated with WG, and that genetic factors may operate independently, as indicated by changes in linkage disequilibrium in patients.
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Objective: To measure markers of atherogenesis and thrombogenesis in patients with rheumatoid arthritis (RA) and in matched controls, and to relate these variables to markers of inflammation and endothelial activation, and to the presence of atherosclerosis.

Methods: Thirty-nine patients with RA with disease onset between 1974 and 1978, who were younger than 65 years at the present study in 1997, were investigated together with 39 age and sex matched controls. IgG, IgA, and IgM antibodies against oxidized low density lipoprotein (oxLDL ab), malondialdehyde LDL (MDA-LDL ab) and cardiolipin (aCL) were measured by ELISA, circulating immune complexes (CIC) were isolated by precipitation, and homocysteine was measured with HPLC.

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Objective: Wegener's granulomatosis (WG) is a necrotizing vasculitis characterized by clonal expansions of T cells and production of antibodies against proteinase 3. The disease is associated with expanded dinucleotide repeats in the cytotoxic T lymphocyte antigen 4 (CTLA-4) gene, suggesting that genetic variation(s) in T cell related gene(s) could contribute to the T cell hyperactivity in WG. We investigated the polymorphisms in the genes of 2 cytokines, interleukin 4 (IL-4) and IL-10, which are essential for the polarization of T cells towards Th2 development and for the Ig production by B cells.

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Objective: To analyze the association of genetic polymorphisms of pro-inflammatory cytokines with rheumatoid arthritis (RA) in comparison with healthy controls from Northern Sweden and the potential contribution of these genetic variants for disease severity and development of cardiovascular complications.

Methods: Polymerase chain reaction amplification was used for analysis of TaqI restriction fragment length polymorphism (RFLP) of interleukin-1 beta (IL-1beta), variable tandem repeat polymorphism of IL-I receptor antagonist (IL-1Ra) gene and NcoI RFLP at position -308 of tumor necrosis factor-alpha (TNF-alpha) gene. One hundred and fifty-four patients with RA, 42 men and 112 women, were consecutively recruited into the study through the Department of Rheumatology.

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