Comparison of circulating and excreted metals and of autoimmunity between two Great Plains Tribal communities.

Metals contaminants of the environment from mine waste have been implicated as contributing agents in autoimmune disease. The current study compares metals and autoimmunity in two Tribal communities residing in the Black Hills and the Bighorn Mountains geographical regions that are scattered with extant hard rock mines. With documented drinking water contamination in both communities, in vivo levels of more than half of the measured serum and urine metals differed between the two communities and were substantially different from their national median values.

Urinary Metals Concentrations and Biomarkers of Autoimmunity among Navajo and Nicaraguan Men.

Metals are suspected contributors of autoimmune disease among indigenous Americans. However, the association between metals exposure and biomarkers of autoimmunity is under-studied. In Nicaragua, environmental exposure to metals is also largely unexamined with regard to autoimmunity.

Elevated autoimmunity in residents living near abandoned uranium mine sites on the Navajo Nation.

Specific autoantibodies were assessed among residents of the Navajo Nation in New Mexico chronically exposed to metal mixtures from uranium mine wastes and in drinking water supplies. Age and the extent of exposure to legacy waste from 100 abandoned uranium mine and mill sites were associated with antibodies to denatured DNA, previously known to be an early indicator of medication-induced autoimmunity. Surprisingly, autoantibodies to native DNA and/or chromatin were also linked to environmental exposure, specifically uranium consumption through drinking water for both men and women, while urinary arsenic was negatively associated with these autoantibodies in women.

Mice Housed at Elevated Vivarium Temperatures Display Enhanced T-cell Response and Survival to .

The inability to translate findings from studies performed in mouse models to the corresponding human condition is well known, especially those involving infectious, atherosclerotic, and other inflammatory diseases. We hypothesize that mice fail to a mount robust or adequate immune response to infectious agents because of physiologic effects of cold stress due to housing temperatures below the mouse thermoneutral zone (TNZ). This hypothesis was tested by comparing the immune response to the Francisella tularensis live vaccine strain in mice housed at a typical vivarium temperature, which is below the TNZ, with that of mice housed at a temperature near their TNZ.

The universe of ANA testing: a case for point-of-care ANA testing.

Testing for total antinuclear antibodies (ANA) is a critical tool for diagnosis and management of autoimmune diseases at both the primary care and subspecialty settings. Repurposing of ANA from a test for lupus to a test for any autoimmune condition has driven the increase in ANA requests. Changes in ANA referral patterns include early or subclinical autoimmune disease detection in patients with low pre-test probability and use of negative ANA results to rule out underlying autoimmune disease.

Biosensor for total antinuclear antibody determination at the point-of-care.

Antinuclear antibodies (ANA) are important in diagnosis and follow-up of patients with autoimmune conditions. The current increase in ANA requests is driven by broadening the use of ANA from a test for lupus to a test for diverse autoimmune diseases, but the standard method is protracted, cumbersome and prone to error. We describe an electrochemical method for quantifying total ANA for use as a point-of-care diagnostic aid.

Drug-induced lupus.

Introduction: Drug-induced lupus (DIL) refers to an idiosyncratic side effect of numerous, apparently unrelated, medications, in which symptoms overlap with those of systemic lupus erythematosus. DIL is reversible by discontinuation of the medication. The etiological mechanism underlying DIL is linked to the inherent susceptibility of the adaptive immune system to lapse into auto-reactivity.

Mercury, autoimmunity, and environmental factors on cheyenne river sioux tribal lands.

Mercury (Hg), shown to induce autoimmune disease in rodents, is a ubiquitous toxicant throughout Cheyenne River Sioux Tribe (CRST) lands. CRST members may be exposed to Hg through fish consumption (FC), an important component of native culture that may supplement household subsistence. Our goals were to ascertain whether total blood Hg levels (THg) reflect Hg exposure through FC and smoking, and determine whether THg is associated with the presence of anti-nuclear antibody (ANA) and specific autoantibodies (sAuAb).

Electrochemical biosensor for quantitation of anti-DNA autoantibodies in human serum.

Measurement of serum autoantibody is a critical tool in the diagnosis and management of autoimmune diseases. However, rapid and convenient methods at the point-of care have not been achieved in large part because any one antibody species is a heterogeneous and miniscule fraction of the total serum immunoglobulin displaying identical properties other than its antigen-binding specificity. The present system addresses these challenges by vacuum-mediated transport of diluted serum through an antigen-coated porous membrane.

Detection of autoantibodies in a point-of-care rheumatology setting.

Autoimmune rheumatic diseases are common and confront society with serious medical, social, and financial burdens imposed by their debilitating nature. Many autoimmune diseases are associated with a particular set of autoantibodies, which have emerged as highly useful to define and classify disease, predict flares, or monitor efficacy of therapy. However, current practice for monitoring autoantibodies is protracted, labor-intensive, and expensive.

Rapid detection of anti-chromatin autoantibodies in human serum using a portable electrochemical biosensor.

The current system employed electrochemical sensor technology for the measurement of autoantibodies in human sera. Anti-chromatin antibodies are an early and sensitive indicator of systemic lupus erythematosus (SLE) and are typically quantified using enzyme-linked immunosorbent assays (ELISA). Electrochemical detection compared favorably with ELISA using a sample of 30 SLE sera (r=0.

Plasticity in the positive selection of T cells: affinity of the selecting antigen and IL-7 affect T cell responsiveness.

The current study examines how responsiveness of T cells is affected by the avidity of the peptide/MHC engaged during positive selection of their thymocyte precursors. We used a thymus reaggregate culture system in which CD4(+)CD8(+) thymocytes from AND TCR transgenic mice were induced to undergo positive selection by pigeon cytochrome c (PCC) peptide or its analogs presented by I-E(k) class II MHC on a thymic epithelial cell line. When low-affinity peptide analogs drove positive selection, up to 100 microM was needed to produce >50% CD4(+) T cells, and these cells were highly responsive to PCC.

Effect of cigarette smoke on autoimmunity in murine and human systemic lupus erythematosus.

Several studies have found that smoking cigarettes is a risk factor for systemic lupus erythematosus (SLE). To examine this issue in a mouse model, we subjected pre-autoimmune MRL-lpr/lpr mice for 4 weeks to cigarette smoke to provide standardized smoke effluents equivalent to moderate or to heavy smoking habits for people. The spontaneous production of IgG anti-chromatin but not IgM anti-chromatin, anti-denatured DNA, or rheumatoid factor antibodies was lower in mice exposed to 250 mg/m3 particulates from mainstream smoke, and this suppression of autoimmunity was sustained for 8 weeks (p < 0.

Drug-induced lupus.

Autoantibodies and, less commonly, systemic rheumatic symptoms are associated with treatment with numerous medications and other types of ingested compounds. Distinct syndromes can be distinguished, based on clinical and laboratory features, as well as exposure history. Drug-induced lupus has been reported as a side-effect of long-term therapy with over 40 medications.

GW182 is critical for the stability of GW bodies expressed during the cell cycle and cell proliferation.

A novel cytoplasmic compartment referred to as GW bodies was initially identified using human autoantibodies to a 182 kDa protein named GW182. GW bodies are small, generally spherical, cytoplasmic domains that vary in number and size in several mammalian cell types examined to date. Based on our earlier studies, GW bodies were proposed to be cytoplasmic sites for mRNA storage and/or degradation.