Biomonitoring of Indoor Air Fungal or Chemical Toxins with Caenorhabditis elegans nematodes.

Bad indoor air quality due to toxins and other impurities can have a negative impact on human well-being, working capacity and health. Therefore, reliable methods to monitor the health risks associated with exposure to hazardous indoor air agents are needed. Here, we have used transgenic Caenorhabditis elegans nematode strains carrying stress-responsive fluorescent reporters and evaluated their ability to sense fungal or chemical toxins, especially those that are present in moisture-damaged buildings. Liquid-based or airborne exposure of nematodes to mycotoxins, chemical agents or damaged building materials reproducibly resulted in time- and dose-dependent fluorescent responses, which could be quantitated by either microscopy or spectrometry. Thus, the C. elegans nematodes present an easy, ethically acceptable and comprehensive in vivo model system to monitor the response of multicellular organisms to indoor air toxicity.

Dysfunction in macrophage toll-like receptor signaling caused by an inborn error of cationic amino acid transport.

Amino acids, especially arginine, are vital for the well-being and activity of immune cells, and disruption of amino acid balance may weaken immunity and predispose to infectious and autoimmune diseases. We present here a model of an inborn aminoaciduria, lysinuric protein intolerance (LPI), in which a single mutation in y(+)LAT1 cationic amino acid transporter gene SLC7A7 leads to a multisystem disease characterized by immunological complications, life-threatening pulmonary alveolar proteinosis and nephropathy. Macrophages are suggested to play a central role in LPI in the development of these severe secondary symptoms. We thus studied the effect of the Finnish y(+)LAT1 mutation on monocyte-derived macrophages where toll-like receptors (TLRs) act as the key molecules in innate immune response against external pathogens. The function of LPI patient and control macrophage TLR signaling was examined by stimulating the TLR2/1, TLR4 and TLR9 pathways with their associated pathogen-associated molecular patterns. Downregulation in expression of TLR9, IRF7, IRF3 and IFNB1 and in secretion of IFN-α was detected, suggesting an impaired response to TLR9 stimulation. In addition, secretion of TNF-α, IL-12 and IL-1RA by TLR2/1 stimulation and IL-12 and IL-1RA by TLR4 stimulation was increased in the LPI patients. LPI macrophages secreted significantly less nitric oxide than control macrophages, whereas plasma concentrations of inflammatory chemokines CXCL8, CXCL9 and CXCL10 were elevated in the LPI patients. In conclusion, our results strengthen the relevance of macrophages in the pathogenesis of LPI and, furthermore, suggest that cationic amino acid transport plays an important role in the regulation of innate immune responses.

Antibodies to deamidated gliadin peptide in diagnosis of celiac disease in children.

OBJECTIVES: Determination of antibodies to synthetic deamidated gliadin peptides (anti-DGPs) may work as an alternative or complement the commonly used test for tissue transglutaminase antibodies (TGA) in the diagnosis of celiac disease (CD). We analyzed the performance of a time-resolved immunofluorometric anti-DGP assay (TR-IFMA) in the diagnosis of CD in children and also retrospectively analyzed the appearance of anti-DGP antibodies before TGA seroconversion. METHODS: The study included 92 children with biopsy-confirmed CD. Serum samples were taken at the time or just before the clinical diagnosis. The control group comprised 82 TGA-negative children who were positive for human leucocyte antigen-DQ2 or -DQ8. RESULTS: Based on receiver operating characteristic curves, the optimal cutoff value for immunoglobulin (Ig) A anti-DGP positivity was 153 arbitrary units (AUs) with a sensitivity of 92.4% and specificity of 97.6% and that for IgG anti-DGP 119 AU, with a sensitivity of 97.8% and specificity of 97.6%. All 92 children with CD were either IgA or IgG anti-DGP positive at the time of diagnosis. Sera from 48 children with CD were also analyzed retrospectively before the diagnosis. Anti-DGP antibodies preceded TGA positivity in 35 of the 48 children with CD and appeared a median of 1 year earlier. CONCLUSIONS: The TR-IFMA assay for detecting anti-DGP antibodies shows high sensitivity and specificity for the diagnosis of CD in children. In a majority of our study population, anti-DGP seropositivity preceded TGA positivity, indicating that earlier detection of CD may be possible by monitoring anti-DGP antibodies frequently in genetically susceptible children.