A feasibility study on exhaled breath analysis using UV spectroscopy to detect COVID-19.

A 23-subject feasibility study is reported to assess how UV absorbance measurements on exhaled breath samples collected from silicon microreactors can be used to detect COVID-19. The silicon microreactor technology chemoselectively preconcentrates exhaled carbonyl volatile organic compounds and subsequent methanol elution provides samples for analysis. The underlying scientific rationale that viral infection will induce an increase in exhaled carbonyls appears to be supported by the results of the feasibility study.

The NOD Mouse Beyond Autoimmune Diabetes.

Autoimmune diabetes arises spontaneously in Non-Obese Diabetic (NOD) mice, and the pathophysiology of this disease shares many similarities with human type 1 diabetes. Since its generation in 1980, the NOD mouse, derived from the Cataract Shinogi strain, has represented the gold standard of spontaneous disease models, allowing to investigate autoimmune diabetes disease progression and susceptibility traits, as well as to test a wide array of potential treatments and therapies. Beyond autoimmune diabetes, NOD mice also exhibit polyautoimmunity, presenting with a low incidence of autoimmune thyroiditis and Sjögren's syndrome.

Insulin-like Growth Factor 1 and Prolactin Levels in Chimpanzees (Pan troglodytes) Across the Lifespan.

As human and chimpanzee genomes show high homology for and , we analyzed the sera of 367 healthy chimpanzees obtained during routine physical examinations in a single colony and measured chimpanzee insulin-like growth factor (IGF)-1 and prolactin (PRL) levels across the lifespan using standard human immunoassays. Assuming chimpanzee IGF-1 levels peak during puberty as in humans, we randomly defined puberty as the age at which most IGF-1 levels were equal to or above the 90 percentile for each sex (males, ages ≥7.00 but <9.

A Mouse Thyrotropin Receptor A-Subunit Transgene Expressed in Thyroiditis-Prone Mice May Provide Insight into Why Graves' Disease Only Occurs in Humans.

Graves' disease, caused by autoantibodies that activate the thyrotropin (TSH) receptor (TSHR), has only been reported in humans. Thyroiditis-prone NOD. mice develop autoantibodies to thyroglobulin (Tg) and thyroid peroxidase (TPO) but not to the TSHR.

Nanoparticles Bearing TSH Receptor Protein and a Tolerogenic Molecule Do Not Induce Immune Tolerance but Exacerbate Thyroid Autoimmunity in hTSHR/NOD. Mice.

Transgenic NOD. mice that express the human (h) TSHR A-subunit in the thyroid gland spontaneously develop pathogenic TSHR autoantibodies resembling those in patients with Graves disease. Nanoparticles coupled to recombinant hTSHR A-subunit protein and a tolerogenic molecule (ligand for the endogenous aryl-hydrocarbon receptor; ITE) were injected i.

To reflect human autoimmune thyroiditis, thyroid peroxidase (not thyroglobulin) antibodies should be measured in female (not sex-independent) NOD.H2 mice.

NOD.H2 mice are the most commonly used model for human autoimmune thyroiditis. Because thyroid autoimmunity develops slowly (over months), NOD.

Thyroid Hemiagenesis in a Thyroiditis Prone Mouse Strain.

Background: Thyroid hemiagenesis, a rare congenital condition detected by ultrasound screening of the neck, is usually not manifested clinically in humans. This condition has been reported in mice with hypothyroidism associated with induced deficiency in paired box 8 and NK2 homeobox 1, sonic hedgehog, or T-box 1. Unexpectedly, we observed thyroid hemiagenesis in NOD.

Aberrant Iodine Autoregulation Induces Hypothyroidism in a Mouse Strain in the Absence of Thyroid Autoimmunity.

We investigated factors underlying the varying effects of a high dietary iodide intake on serum T4 levels in a wide spectrum of mouse strains, including thyroiditis-susceptible NOD.H2, NOD.H2, and NOD mice, as well as other strains (BALB/c, C57BL/6, NOD.

Variable Effects of Dietary Selenium in Mice That Spontaneously Develop a Spectrum of Thyroid Autoantibodies.

Selenium (Se) is a critical element in thyroid function, and variable dietary Se intake influences immunity. Consequently, dietary Se could influence development of thyroid autoimmunity and provide an adjunct to treat autoimmune thyroid dysfunction. Nonobese diabetic (NOD).

Genes Outside the Major Histocompatibility Complex Locus Are Linked to the Development of Thyroid Autoantibodies and Thyroiditis in NOD.H2h4 Mice.

Thyroiditis and autoantibodies to thyroglobulin (TgAb) and thyroid peroxidase (TPOAb) develop spontaneously in NOD.H2h4 mice, a phenotype enhanced by dietary iodine. NOD.

High-level intrathymic thyrotrophin receptor expression in thyroiditis-prone mice protects against the spontaneous generation of pathogenic thyrotrophin receptor autoantibodies.

The thyrotrophin receptor (TSHR) A-subunit is the autoantigen targeted by pathogenic autoantibodies that cause Graves' hyperthyroidism, a common autoimmune disease in humans. Previously, we reported that pathogenic TSHR antibodies develop spontaneously in thyroiditis-susceptible non-obese diabetic (NOD).H2 mice bearing a human TSHR A-subunit transgene, which is expressed at low levels in both the thyroid and thymus (Lo-expressor transgene).

Critical Differences between Induced and Spontaneous Mouse Models of Graves' Disease with Implications for Antigen-Specific Immunotherapy in Humans.

Graves' hyperthyroidism, a common autoimmune disease caused by pathogenic autoantibodies to the thyrotropin (TSH) receptor (TSHR), can be treated but not cured. This single autoantigenic target makes Graves' disease a prime candidate for Ag-specific immunotherapy. Previously, in an induced mouse model, injecting TSHR A-subunit protein attenuated hyperthyroidism by diverting pathogenic TSHR Abs to a nonfunctional variety.

Evidence that TSH Receptor A-Subunit Multimers, Not Monomers, Drive Antibody Affinity Maturation in Graves' Disease.

Context: The TSH receptor (TSHR) A-subunit shed from the cell surface contributes to the induction and/or affinity maturation of pathogenic TSHR autoantibodies in Graves' disease.

Objective: This study aimed to determine whether the quaternary structure (multimerization) of shed A-subunits influences pathogenic TSHR autoantibody generation.

Design: The isolated TSHR A-subunit generated by transfected mammalian cells exists in two forms; one (active) is recognized only by Graves' TSHR autoantibodies, the second (inactive) is recognized only by mouse monoclonal antibody (mAb) 3BD10.

A unique mouse strain that develops spontaneous, iodine-accelerated, pathogenic antibodies to the human thyrotrophin receptor.

Abs that stimulate the thyrotropin receptor (TSHR), the cause of Graves' hyperthyroidism, only develop in humans. TSHR Abs can be induced in mice by immunization, but studying pathogenesis and therapeutic intervention requires a model without immunization. Spontaneous, iodine-accelerated, thyroid autoimmunity develops in NOD.

Evidence that MHC I-E dampens thyroid autoantibodies and prevents spreading to a second thyroid autoantigen in I-A(k) NOD mice.

NOD.H2(k) and NOD.H2(h4) mice carry the major histocompatibility complex (MHC) class II molecule I-A(k) associated with susceptibility to experimentally induced thyroiditis.

Immunoglobulin heavy chain variable region and major histocompatibility region genes are linked to induced graves' disease in females from two very large families of recombinant inbred mice.

Graves' hyperthyroidism is caused by antibodies to the TSH receptor (TSHR) that mimic thyroid stimulation by TSH. Stimulating TSHR antibodies and hyperthyroidism can be induced by immunizing mice with adenovirus expressing the human TSHR A-subunit. Prior analysis of induced Graves' disease in small families of recombinant inbred (RI) female mice demonstrated strong genetic control but did not resolve trait loci for TSHR antibodies or elevated serum T4.

Sex, genetics, and the control of thyroxine and thyrotropin in mice.

Background: Previously, we studied the genetic basis for variability in total thyroxine (TT4) as part of investigating induced Graves' hyperthyroidism in panels of genetically diverse recombinant inbred (RI) mice. Because Graves' disease occurs predominantly in women, we used female mice. A limitation of this approach is that thyrotropin (TSH) is undetectable by some assays in most female mice.

Thyroid autoantibodies are rare in nonhuman great apes and hypothyroidism cannot be attributed to thyroid autoimmunity.

The great apes include, in addition to Homo, the genera Pongo (orangutans), Gorilla (gorillas), and Pan, the latter comprising two species, P. troglodytes (chimpanzees) and P. paniscus (bonobos).

Genetic linkages for thyroxine released in response to thyrotropin stimulation in three sets of recombinant inbred mice provide evidence for shared and novel genes controlling thyroid function.

Background: Graves' hyperthyroidism is induced by immunizing mice with adenovirus expressing the human thyrotropin (TSH)-receptor. Using families of recombinant-inbred mice, we previously discovered that genetic susceptibility to induced thyroid-stimulating antibodies and hyperthyroidism are linked to loci on different chromosomes, indicating a fundamental genetic difference in thyroid sensitivity to ligand stimulation. An approach to assess thyroid sensitivity involves challenging genetically diverse lines of mice with TSH and measuring the genotype/strain-specific increase in serum thyroxine (T4).

Breaking tolerance in transgenic mice expressing the human TSH receptor A-subunit: thyroiditis, epitope spreading and adjuvant as a 'double edged sword'.

Transgenic mice with the human thyrotropin-receptor (TSHR) A-subunit targeted to the thyroid are tolerant of the transgene. In transgenics that express low A-subunit levels (Lo-expressors), regulatory T cell (Treg) depletion using anti-CD25 before immunization with adenovirus encoding the A-subunit (A-sub-Ad) breaks tolerance, inducing extensive thyroid lymphocytic infiltration, thyroid damage and antibody spreading to other thyroid proteins. In contrast, no thyroiditis develops in Hi-expressor transgenics or wild-type mice.

Role of self-tolerance and chronic stimulation in the long-term persistence of adenovirus-induced thyrotropin receptor antibodies in wild-type and transgenic mice.

Background: Graves'-like disease, reflected by thyrotropin receptor (TSHR) antibodies and hyperthyroidism in some mouse strains, can be induced by immunization with adenovirus-expressing DNA for the human TSHR or its A-subunit. The conventional approach involves two or three adenovirus injections at 3-week intervals and euthanasia 10 weeks after the first injection. To investigate TSHR antibody persistence in mice with differing degrees of self-tolerance to the TSHR A-subunit, we studied the effect of delaying euthanasia until 20 weeks after the initial immunization.

Long term persistence of thyrotropin receptor antibodies in wild-type and transgenic mice in a Graves' disease model.

Background: Graves'-like disease, reflected by TSHR antibodies and hyperthyroidism in some mouse strains, can be induced by immunization with adenovirus expressing DNA for the human thyrotropin receptor (TSHR) or it's A-subunit. The conventional approach involves two or three adenovirus injections at three-weekly intervals and euthanasia 10 weeks after the first injection. In order to investigate TSHR antibody persistence in mice with differing degrees of self-tolerance to the TSHR A-subunit, we studied the effect of delaying euthanasia until 20 weeks after the initial immunization.

Exceptional hyperthyroidism and a role for both major histocompatibility class I and class II genes in a murine model of Graves' disease.

Autoimmune hyperthyroidism, Graves' disease, can be induced by immunizing susceptible strains of mice with adenovirus encoding the human thyrotropin receptor (TSHR) or its A-subunit. Studies in two small families of recombinant inbred strains showed that susceptibility to developing TSHR antibodies (measured by TSH binding inhibition, TBI) was linked to the MHC region whereas genes on different chromosomes contributed to hyperthyroidism. We have now investigated TSHR antibody production and hyperthyroidism induced by TSHR A-subunit adenovirus immunization of a larger family of strains (26 of the AXB and BXA strains).

An attempt to induce "Graves' disease of the gonads" by immunizing mice with the luteinizing hormone receptor provides insight into breaking tolerance to self-antigens.

Background: Gonadotropin receptors, unlike the thyrotropin receptor (TSHR), are not cleaved into disulfide-linked A- and B-subunits, nor do they shed A-subunits. Heavily glycosylated TSHR A-subunits initiate or amplify responses leading to stimulating TSHR-autoantibodies and Graves' hyperthyroidism.

Methods: To investigate the possibility that mice immunized with luteinizing hormone receptor (LHR) would develop functional antibodies, we constructed adenoviruses expressing the rat-LH holoreceptor (LHR-Ad) and an LHR A-subunit equivalent (LHR-289-Ad).