Appraising SARS-CoV-2 infections after full mRNA COVID-19 vaccination in patients with systemic lupus erythematosus (SLE)☆
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ABSTRACT:
SUBMITTER: Anuforo A
PROVIDER: S-EPMC8906889 | biostudies-literature | 2022 Mar
REPOSITORIES: biostudies-literature
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Project description:IntroductionTLR7/8 and TLR9 signaling pathways have been extensively studied in systemic lupus erythematosus (SLE) as possible mediators of disease. Monocytes are a major source of pro-inflammatory cytokines and are understudied in SLE. In the current project, we investigated sex differences in monocyte activation and its implications in SLE disease pathogenesis.MethodsHuman blood samples from 27 healthy male controls, 32 healthy female controls, and 25 female patients with SLE matched for age and race were studied. Monocyte activation was tested by flow cytometry and ELISA, including subset proportions, CD14, CD80 and CD86 expression, the percentage of IL-6-producing monocytes, plasma levels of sCD14 and IL-6, and urine levels of creatinine.ResultsMonocytes were significantly more activated in women compared to men and in patients with SLE compared to controls in vivo. We observed increased proportions of non-classic monocytes, decreased proportions of classic monocytes, elevated levels of plasma sCD14 as well as reduced surface expression of CD14 on monocytes comparing women to men and lupus patients to controls. Plasma levels of IL-6 were positively related to sCD14 and serum creatinine.ConclusionMonocyte activation and TLR4 responsiveness are altered in women compared to men and in patients with SLE compared to controls. These sex differences may allow persistent systemic inflammation and resultant enhanced SLE susceptibility.
| S-EPMC4259347 | biostudies-literature
Project description:Juvenile-onset systemic lupus erythematosus (jSLE) is an autoimmune disorder with multifaceted clinical findings in different organ systems. Neuropsychiatric manifestations affect more than half of SLE patients, and there is increasing evidence that anorexia nervosa (AN), a feeding and eating disorder (FED) characterized by significantly reduced energy intake, is among them. Herein, a review of the literature on the potential association between jSLE and AN was performed. Reported clinical cases were identified, and putative pathophysiological mechanisms were sought that could potentially explain the observed relationship between these two pathological entities. Four reports of isolated cases and a case series including seven patients were identified. In this limited patient pool, the diagnosis of AN preceded that of SLE in the majority of cases, whereas in all cases both entities were diagnosed within a time span of two years. Many explanations for the observed relationships have been proposed. AN has been associated with the stress of chronic disease diagnosis; on the other hand, the chronic inflammation associated with AN may contribute to the development/appearance of SLE. Adverse childhood experiences, concentrations of leptin, shared autoantibodies, and genetic traits appear to be important factors in this well-established interplay. In essence, it seems important to increase clinician awareness of the concomitant development of AN and SLE and invite further research on the subject.
| S-EPMC10137086 | biostudies-literature
Project description:In the wake of the Portuguese vaccination program 50th anniversary it seems appropriate to review vaccination in patients with systemic lupus erythematosus. Controversial issues as regards the association between autoimmune diseases, infections, and vaccines are discussed as well as vaccine safety and efficacy issues as regards chronic immunosuppressant (IS) drug therapy. After a brief overview of national policies, specific recommendations are made as regards vaccination for adult patients with SLE with a particular focus on current IS therapy and unmet needs.
| S-EPMC4812392 | biostudies-other
Project description:Engagement of the CD3/T cell receptor complex in systemic lupus erythematosus (SLE) T cells involves Syk rather than the zeta-associated protein. Because Syk is being considered as a therapeutic target we asked whether Syk is central to the multiple aberrantly modulated molecules in SLE T cells. Using a gene expression array, we demonstrate that forced expression of Syk in normal T cells reproduces most of the aberrantly expressed molecules whereas silencing of Syk in SLE T cells normalizes the expression of most abnormally expressed molecules. Protein along with gene expression modulation for select molecules was confirmed. Specifically, levels of cytokine IL-21, cell surface receptor CD44, and intracellular molecules PP2A and OAS2 increased following Syk overexpression in normal T cells and decreased after Syk silencing in SLE T cells. Our results demonstrate that levels of Syk affect the expression of a number of enzymes, cytokines and receptors that play a key role in the development of disease pathogenesis in SLE and provide support for therapeutic targeting in SLE patients.
| S-EPMC3754955 | biostudies-literature
Project description:Systemic lupus erythematosus (SLE) is a complex autoimmune rheumatic disease with multiple presentations, whose management presents many challenges. Many disease modifying or immunosuppressive drugs have been used with limited success, especially in patients with more severe disease activity. Belimumab is the first drug to be approved specifically for the treatment of SLE in more than 50 years. By blocking the B-cell activating factor, it interferes in B-cell differentiation and survival. Here we consider the results of the clinical trials that led to its approval, as well as the post-hoc analyses, follow-up studies and the current trials.
| S-EPMC5349337 | biostudies-literature
Project description:An in-depth literature review of up to 2023 reveals 330 risk loci found by genetic association at p ≤ 5 × 10-8, with systemic lupus erythematosus (SLE) in at least one study of 160 pertinent publications. There are 225 loci found in East Asian (EAS), 106 in European (EU), 11 in African-American (AA), 18 Mixed American (MA), and 1 in Egyptian ancestries. Unexpectedly, most of these associations are found to date at p ≤ 5 × 10-8 in a single ancestry. However, the EAS and EU share 40 risk loci that are independently established. The great majority of the identified loci [250 (75.8%) of 330] do not contain a variant that changes an amino acid sequence. Meanwhile, most overlap with known regulatory elements in the genome [266 (80.6%) of 330], suggesting a major role for gene regulation in the genetic mechanisms of SLE. To evaluate the pathways altered by SLE-associated variants, we generated gene sets potentially regulated by SLE loci that consist of the nearest genes, published attributions, and genes predicted by computational tools. The most useful insights, at present, suggest that SLE genetic mechanisms involve (1) the regulation of both adaptive and innate immune responses including immune cell activation and differentiation; (2) the regulation of production and response to cytokines, including type I interferon; (3) apoptosis; (4) the sensing and removal of immune complexes and apoptotic particles; and (5) immune response to infections, including Epstein-Barr Virus, and symbiont microorganisms. These mechanisms affected by SLE genes involve multiple cell types, including B cells/plasma cells, T cells, dendritic cells, monocytes/macrophages, natural killer cells, neutrophils, and endothelial cells. The genetics of SLE from GWAS data reveal an incredibly complex profusion of interrelated molecular processes and interacting cells participating in SLE pathogenesis, mostly unified in the molecular regulation of inflammatory responses. These genetic associations in lupus and affected molecular pathways not only give us an understanding of the disease pathogenesis but may also help in drug discoveries for SLE treatment.
| S-EPMC11609870 | biostudies-literature
Project description:FAS/FASL system plays a central role in maintaining peripheral immune tolerance. Human Systematic Lupus Erythematosus (SLE) is a prototypic systemic autoimmune disease characterized by expansion of autoreactive lymphocytes. It remains unclear whether a defective FAS/FASL system is involved in the pathogenesis of SLE. In this study, we have discovered a novel nucleotide insertion in FAS mRNA. We demonstrate that this novel FAS mutation occurs at mRNA levels, likely through a site-specific mRNA editing process. The mRNA editing mutation is unique for human FAS because the similar mRNA editing event is absent in other human TNF receptor (TNFR) family genes with death domains (DR5, DR6, and TNFR1) and in murine FAS. The adenine insertion mutation in the coding region message causes the alteration of human FAS mRNA reading frame. Functionally, cells expressing the edited FAS (edFAS) were refractory to FAS-mediated apoptosis. Surprisingly, cells from SLE patients produced significantly more edFAS products compared to cells from normal healthy controls. Additionally, we demonstrated that persistent engagement of T-cell receptor increases human FAS mRNA editing in human T cells. Our data suggest that the site-specific FAS mRNA editing mutation may play a critical role in human immune responses and in the pathogenesis of human chronic inflammatory diseases.
| S-EPMC3196739 | biostudies-literature
Project description:Foot complaints have been shown to be common in systemic lupus erythematosus (SLE) and heterogeneous in nature. We aimed to categorize self-reported foot complaints in people with SLE and foot symptoms.A self-administered validated questionnaire was posted to 406 people with SLE attending adult rheumatology clinics across three health boards in Auckland, New Zealand. In addition to foot pain, vascular complaints, dermatological lesions and neurological symptoms were included in the analysis. Pairwise correlations among the variables were undertaken followed by factor analysis to identify and categorise associations between reported foot complaints.From the questionnaires returned, 93 full datasets were analysed. Participants' were predominantly female (n = 87, 93.7%), with mean (SD) age of 50.4 (14.3) years and a mean (SD) disease duration of 13.1 (11) years. Three categories of foot complaint were determined: 'foot pain', 'skin disorders' and 'vascular insufficiency'. These three groups provided the best fit (0.91) to describe the wide range of foot complaints reported by those with SLE. Factor analysis for foot pain demonstrated a high positive loading for the inter-correlation of foot pain in past month (0.83), foot pain today (0.71), intermittent claudication (0.71), numbness (0.62), loss of balance (0.81), swelling (0.59), foot joint pain (0.77), arch pain (0.68) and tendon pain (0.77). Skin disorders demonstrated a very high positive loading for 3 factors skin rash (0.82), blistering skin rash (0.95) and foot ulceration (0.88). In vascular insufficiency a high positive loading for cold feet (0.83), chilblains (0.76) and Raynaud's phenomenon (0.70).This work suggests people with SLE report three independent categories of foot complaints; foot pain, skin disorders or vascular insufficiency.
| S-EPMC5530459 | biostudies-other
Project description:Systemic lupus erythematosus (SLE) is a complex autoimmune disorder with multiple susceptibility genes. We have previously reported suggestive linkage to the chromosomal region 14q21-q23 in Finnish SLE families.Genetic fine mapping of this region in the same family material, together with a large collection of parent affected trios from UK and two independent case-control cohorts from Finland and Sweden, indicated that a novel uncharacterized gene, MAMDC1 (MAM domain containing glycosylphosphatidylinositol anchor 2, also known as MDGA2, MIM 611128), represents a putative susceptibility gene for SLE. In a combined analysis of the whole dataset, significant evidence of association was detected for the MAMDC1 intronic single nucleotide polymorphisms (SNP) rs961616 (P -value = 0.001, Odds Ratio (OR) = 1.292, 95% CI 1.103-1.513) and rs2297926 (P -value = 0.003, OR = 1.349, 95% CI 1.109-1.640). By Northern blot, real-time PCR (qRT-PCR) and immunohistochemical (IHC) analyses, we show that MAMDC1 is expressed in several tissues and cell types, and that the corresponding mRNA is up-regulated by the pro-inflammatory cytokines tumour necrosis factor alpha (TNF-alpha) and interferon gamma (IFN-gamma) in THP-1 monocytes. Based on its homology to known proteins with similar structure, MAMDC1 appears to be a novel member of the adhesion molecules of the immunoglobulin superfamily (IgCAM), which is involved in cell adhesion, migration, and recruitment to inflammatory sites. Remarkably, some IgCAMs have been shown to interact with ITGAM, the product of another SLE susceptibility gene recently discovered in two independent genome wide association (GWA) scans.Further studies focused on MAMDC1 and other molecules involved in these pathways might thus provide new insight into the pathogenesis of SLE.
| S-EPMC2785483 | biostudies-literature
Project description: Not available
| S-EPMC9521746 | biostudies-literature