A5089587112- Systemic Lupus Erythematosus Research
- T-cell and B-cell Immunology
- Renal Diseases and Glomerulopathies
- Monoclonal and Polyclonal Antibodies Research
- Immune Cell Function and Interaction
- Cell Adhesion Molecules Research
- Complement system in diseases
- Immunotherapy and Immune Responses
- Chronic Kidney Disease and Diabetes
- Acute Kidney Injury Research
- Atherosclerosis and Cardiovascular Diseases
- Vasculitis and related conditions
- Phagocytosis and Immune Regulation
- Coagulation, Bradykinin, Polyphosphates, and Angioedema
- Reproductive System and Pregnancy
- Autoimmune Bullous Skin Diseases
- Blood groups and transfusion
- Renal and Vascular Pathologies
- Enzyme Structure and Function
- RNA and protein synthesis mechanisms
- Platelet Disorders and Treatments
- Mast cells and histamine
- Liver Diseases and Immunity
- Pregnancy and Medication Impact
- Advances in Oncology and Radiotherapy
Maine Medical Center
2024
Medical University of South Carolina
2021
University of Massachusetts Chan Medical School
2021
Augusta University
2010-2019
Georgia Regents Medical Center
2014-2017
Rochester Institute of Technology
2013-2017
Washington University in St. Louis
2016
Agency for Healthcare Research and Quality
2014
University at Albany, State University of New York
2013-2014
Ospedale Maggiore
2014
The precise role of B cells in systemic autoimmunity is incompletely understood. Although are necessary for expression disease (Chan, O., and M.J. Shlomchik. 1998. J. Immunol. 160:51–59, Shlomchik, M.J., M.P. Madaio, D. Ni, M. Trounstine, Huszar. 1994. Exp. Med. 180:1295–1306), it unclear whether autoantibody production, antigen presentation, and/or other cell functions required the complete pathologic phenotype. To address this issue, two experimental approaches were used. In first,...
The only established role for complement in mediating immunologic renal disease involves elaboration of leukochemotactic factors and neutrophil-dependent glomerular injury. In the passive Heymann nephritis (PHN) model experimental membranous nephropathy, rats injected with sheep antibody to rat proximal tubular brush border antigen (Fx1A) form subepithelial deposits IgG (C3), develop heavy proteinuria after 5 d without inflammatory changes. To study PHN, 16 were treated daily cobra venom...
The primary roles of T cells and B in the initiation systemic autoimmunity are unclear. To investigate role cells, we crossed "Jh knockout" mutation onto autoimmune lpr/lpr background. Animals homozygous for both traits were obtained. As expected, these animals lack cells. These also show no signs kidney destruction nor vasculitis, spite carrying mutation. In contrast, littermates that had severe nephritis as well autoantibodies. results demonstrate a and/or (auto)antibodies initiating...
Idiotypic cross-reactions were evaluated in 60 polynucleotide-binding monoclonal lupus autoantibodies produced by human-human hybridomas that derived from seven unrelated patients with SLE. Three antiidiotype reagents prepared immunization of rabbits or a mouse two patients. Binding the three to their corresponding idiotypes was inhibited one more polynucleotides, an indication antiidiotypes reacted variable regions autoantibodies. Each appeared detect different idiotypic determinant. Of...
Introduction of heterologous anti-glomerular basement membrane antiserum (nephrotoxic serum, NTS) into presensitized mice triggers the production IgG anti-NTS antibodies that are predominantly IgG2b and glomerular deposition pathogenic immune complexes, leading to accelerated renal disease. The pathology observed in this model is determined by effector cell activation threshold established coexpression on infiltrating macrophages IgG2a/2b restricted receptor FcgammaRIV its inhibitory...
A unique subset of anti-DNA antibodies enters living cells, interacts with DNase 1, and inhibits endonuclease activity, before their nuclear localization subsequent attenuation apoptosis. We now report that endocytosis these immunoglobulins is mediated by cell surface binding to brush border myosin (myosin 1). Cellular entry internalization via this receptor provides initial contact for sorting translocate the pore enter nucleus, interact 1 within cytoplasm, or recycle back surface. This...
Abstract MRL/MpJ-Tnfrsf6lpr (MRL/MpJ-Faslpr; MRL-Faslpr) mice develop a spontaneous lupus syndrome closely resembling human systemic erythematosus. To define the role of IL-10 in regulation murine lupus, gene-deficient (IL-10−/−) MRL-Faslpr (MRL-Faslpr IL-10−/−) were generated and their disease phenotype was compared with littermates one or two copies an intact locus IL-10+/− IL-10+/+ mice, respectively). IL-10−/− developed severe earlier appearance skin lesions, increased lymphadenopathy,...
Abstract To test the possibility that anti-DNA antibody formation in autoimmune disease is related to an exceptional responsiveness nucleic acid immunogens, we examined ability of normal and strains mice produce antibodies after immunization with DNA synthetic helical analogues. Autoimmune (MRL/++) did not respond significantly denatured DNA-methylated BSA adjuvant (in comparison alone). They did, however, structures differed from B-DNA, including poly-(dG) . poly(dC), poly(dT-dG)...
To investigate the capacity of lupus autoAb to produce glomerular immune deposits (ID) and nephritis, 24 murine monoclonal (m) anti-DNA antibodies (Ab), derived from either MRL-lpr/lpr, SNF1 or NZB lupus-prone mice selected based on properties shared with nephritogenic Ig, were administered i.p. (as hybridomas) i.v. purified Ig) normal mice; at least four mice/mAb evaluated. Three general patterns deposit formation (IDF) observed: extracellular ID within glomeruli (+/- blood vessels, N = 8);...
AbstractWe identified potential epigenetic biomarkers for chronic kidney disease progression by comparing site-specific DNA methylation levels in more than 14,000 genes between African American and Hispanic diabetes patients with end stage renal (ESRD) without nephropathy. We 187 that are differentially methylated the two groups on at least CpG sites each gene extracted from saliva. Of whose mean differed groups, 39 genes, or closely related family members, have been reported to be involved...
The production of relatively high quantities autoantibodies (autoAb) that react with DNA and other intranuclear antigens is characteristic individuals systemic lupus erythematosus autoimmune diseases. However, the capacity these Ab to penetrate cells induce functional perturbations in vivo not well appreciated. To address this issue, monoclonal (m) anti-DNA (mAb), derived from MRL-lpr/lpr (NZB x SWR)F1 mice, were administered normal animals examined for morphologic abnormalities. A subset...
<h3>Objectives</h3> Malingering can be defined as the abuse of right to benefit from health services. In this study, frequency malingering cases in Basic Military Training Centres (BMTCs) and behaviours attitudes military physicians towards recruits who are suspected malingerers were described. <h3>Method</h3> A total 17 general practitioners nine different BMTCs regions Turkey constitute universe descriptive study. questionnaire, there a 30 questions about characteristics participants their...
Significance Metabolic stress potently modifies immunity. Recently our laboratory identified the kinase GCN2 as a key modulator of macrophage responses to toll-like receptor ligands; however, role myeloid signals in sterile inflammation and homeostatic tolerance is not known. In this study, we tested requirement for apoptotic cells prevention autoimmunity model lupus. Our results show that critical effector cell-driven required regulatory cytokine production inflammatory Moreover, data...
To investigate the mechanism by which interferon-α (IFNα) accelerates systemic lupus erythematosus (SLE) in (NZB×NZW)F1 (NZB/NZW) mice.NZB/NZW mice were treated with an adenovirus expressing IFNα. In some mice, T cells depleted anti-CD4 antibody. The production of anti-double-stranded DNA (anti-dsDNA) antibodies was measured enzyme-linked immunosorbent assay and immunospot assay. Germinal centers antibody-secreting (ASCs) spleens IgG deposition leukocyte infiltrates kidneys visualized...
Antigen-specific Abs are able to enhance or suppress immune responses depending on the receptors that they bind cells. Recent studies have shown pro- antiinflammatory effector functions of IgG also regulated through their Fc N-linked glycosylation patterns. agalactosylated (non-galactosylated) and asialylated proinflammatory induced by combination T cell-dependent (TD) protein antigens costimulation. Sialylated Abs, which immunosuppressive, Tregs produced in presence TD under tolerance...
Renal targets of autoimmunity in human lupus nephritis (LN) are unknown. We sought to identify autoantibodies and glomerular target antigens renal biopsy samples from patients with LN determine whether the same can be detected circulation. Glomeruli were microdissected 20 characterized by proteomic techniques. Serum large cohorts systemic erythematosus (SLE) without other glomerulonephritides tested. Glomerular IgGs recognized 11 podocyte antigens, reactivity varying pathology. Notably, IgG2...
Fairlearn is an open source project to help practitioners assess and improve fairness of artificial intelligence (AI) systems. The associated Python library, also named fairlearn, supports evaluation a model's output across affected populations includes several algorithms for mitigating issues. Grounded in the understanding that sociotechnical challenge, integrates learning resources aid considering system's broader societal context.
B cells are required for both the expression of lupus nephritis and spontaneous T cell activation/memory accumulation in MRL-Faslpr mice (MRL/lpr). Autoimmunity MRL/lpr strain is result Fas-deficiency multiple background genes; however, precise roles genes vs have not been fully defined. (i.e., lpr defect) optimal autoantibody expression, raising possibility that central role may extend to MRL/+ and, thus, models do depend on ("polygenic lupus"). To address this issue, cell-deficient,...
Abstract Although many studies have demonstrated a pathogenic role for alphabeta T cells in murine lupus, little work has addressed gammadelta cells. Here, the roles of and pathogenesis systemic autoimmunity were investigated by generating lupus-prone mice deficient and/or Mice developed an exacerbated disease phenotype compared with that cell-intact mice, consisting augmented hypergammaglobulinemia autoantibody production, more severe renal disease, increased mortality, associated...
To investigate the possibility that non-alpha beta T cell-dependent mechanisms can induce systemic autoimmune disease, and to address roles of alpha cells in murine lupus, we analyzed lupus-prone MRL mice congenitally deficient cells. Surprisingly, TCR-alpha-/- developed several characteristics human lupus erythematosus, including hypergammaglobulinemia, autoantibodies against DNA small nuclear ribonucleoproteins, immune deposits kidneys. These results, which contrast with past studies...
Abstract NZB/W F1 mice with established nephritis were treated a single dose of cyclophosphamide or without 2-wk course murine CTLA4Ig, either alone in combination anti-CD154. Sixty to 80% entered remission, and remission could be reinduced following relapse. A decrease the frequency anti-DNA-producing B cells activated T was observed mice, but this effect lasted only 3–6 wk, while remissions sustained for up 20 wk. Light microscopy kidneys revealed less glomerular inflammation, tubular...