Immuno-reactive proteins from Mycobacterium immunogenum useful for serodiagnosis of metalworking fluid hypersensitivity pneumonitis.

Metalworking fluid-associated hypersensitivity pneumonitis (MWF-HP) is a pulmonary disease caused by inhaling microorganisms present in the metalworking fluids used in the industrial sector. Mycobacterium immunogenum is the main etiological agent. Among the clinical, radiological and biological tools used for diagnosis, serological tests are important. The aim of this study was to identify immunogenic proteins in M. immunogenum and to use recombinant antigens for serological diagnosis of MWF-HP. Immunogenic proteins were detected by two-dimensional Western blot and candidate proteins were identified by mass spectrometry. Recombinant antigens were expressed in Escherichia coli and tested by enzyme-linked immunosorbent assay (ELISA) with the sera of 14 subjects with MWF-HP and 12 asymptomatic controls exposed to M. immunogenum. From the 350 spots visualized by two-dimensional gel electrophoresis with M. immunogenum extract, 6 immunogenic proteins were selected to be expressed as recombinant antigens. Acyl-CoA dehydrogenase antigen allowed for the best discrimination of MWF-HP cases against controls with an area under the receiver operating characteristics (ROC) curve of 0.930 (95% CI=0.820-1), a sensitivity of 100% and a specificity of 83% for the optimum threshold. Other recombinant antigens correspond to acyl-CoA dehydrogenase FadE, cytosol aminopeptidase, dihydrolipoyl dehydrogenase, serine hydroxymethyltransferase and superoxide dismutase. This is the first time that recombinant antigens have been used for the serodiagnosis of hypersensitivity pneumonitis. The availability of recombinant antigens makes it possible to develop standardized serological tests which in turn could simplify diagnosis, thus making it less invasive.

The protein phosphatase 7 regulates phytochrome signaling in Arabidopsis.

The psi2 mutant of Arabidopsis displays amplification of the responses controlled by the red/far red light photoreceptors phytochrome A (phyA) and phytochrome B (phyB) but no apparent defect in blue light perception. We found that loss-of-function alleles of the protein phosphatase 7 (AtPP7) are responsible for the light hypersensitivity in psi2 demonstrating that AtPP7 controls the levels of phytochrome signaling. Plants expressing reduced levels of AtPP7 mRNA display reduced blue-light induced cryptochrome signaling but no noticeable deficiency in phytochrome signaling. Our genetic analysis suggests that phytochrome signaling is enhanced in the AtPP7 loss of function alleles, including in blue light, which masks the reduced cryptochrome signaling. AtPP7 has been found to interact both in yeast and in planta assays with nucleotide-diphosphate kinase 2 (NDPK2), a positive regulator of phytochrome signals. Analysis of ndpk2-psi2 double mutants suggests that NDPK2 plays a critical role in the AtPP7 regulation of the phytochrome pathway and identifies NDPK2 as an upstream element involved in the modulation of the salicylic acid (SA)-dependent defense pathway by light. Thus, cryptochrome- and phytochrome-specific light signals synchronously control their relative contribution to the regulation of plant development. Interestingly, PP7 and NDPK are also components of animal light signaling systems.

Parent perceived quality of life is age-dependent in children with food allergy.

Food allergy in children significantly affects their quality of life. Its impact can be analyzed by quality of life questionnaires. The aim of our study was to validate the French version of disease-specific questionnaires and to evaluate the quality of life in children with IgE-mediated food allergy. Two validated food allergy-specific questionnaires for quality of life, the parent's and children's forms (FAQLQ-PF and FAQLQ-CF), were translated from English to French and submitted to children with food allergy and their parents. Questionnaires were analyzed in terms of emotional impact, food anxiety, and social and food limitations. NCT 01480427. Sixty-two parents of children aged 0-12 yrs answered the FAQLQ-PF, and 32 children aged 8-12 yrs the FAQLQ-CF. Construct validity of both questionnaires was assessed by correlation between the FAQLQs and FAIM (r = 0.85 and 0.84, respectively). Both FAQLQs had good internal consistency (Cronbach's α = 0.748 and 0.67, respectively). Young children (0-3 yrs old) showed better quality of life scores than older children (FAQLQ-PF global score: p = 0.02). Worse scores were also shown among children with previous severe systemic reactions (FAQLQ-PF global score: p = 0.039), the ones with an allergic mother (FAQLQ-PF global score: p = 0.002), or allergic siblings (FAQLQ-PF emotional impact score: p = 0.034), the ones with multiple food allergy (more than 1 food) (FAQLQ-PF anxiety score: p = 0.04) and among the girls (FAQLQ-CF global score: p = 0.031). Older children, the ones with severe systemic reactions, or with mothers or siblings also affected by allergies, as well as girls, and children with multiple food allergies show worse quality of life scores.

Pharmacogenomics of HIV Therapy: Summary of a Workshop Sponsored by the National Institute of Allergy and Infectious Diseases

Approximately 1 million people in the United States and over 30 million worldwide are living with human immunodeficiency virus type 1 (HIV-1). While mortality from untreated infection approaches 100%, survival improves markedly with use of contemporary antiretroviral therapies (ART). In the United States, 25 drugs are approved for treating HIV-1, and increasing numbers are available in resource-limited countries. Safe and effective ART is a cornerstone in the global struggle against the acquired immunodeficiency syndrome. Variable responses to ART are due at least in part to human genetic variants that affect drug metabolism, drug disposition, and off-site drug targets. Defining effects of human genetic variants on HIV treatment toxicity, efficacy, and pharmacokinetics has far-reaching implications. In 2010, the National Institute of Allergy and Infectious Diseases sponsored a workshop entitled, Pharmacogenomics A Path Towards Personalized HIV Care. This article summarizes workshop objectives, presentations, discussions, and recommendations derived from this meeting.

Prevalence of ragweed allergy in rural Geneva - a pilot study.

OBJECTIVE: The prevalence of ragweed allergy is increasing worldwide. Ragweed distribution and abundance is spreading in Europe in a wide area ranging from the Rhone valley in France to Hungary and Ukraine, where the rate of the prevalence can peak at as high as 12%. Low-grade ragweed colonisation was seen in Geneva and Ticino, less than two decades ago. There were fears that allergies to ragweed would increase Switzerland. The intent of this study was to assess the rate of prevalence of sensitisation and allergy to ragweed in the population living in the first rural Swiss setting where ragweed had been identified in 1996, and to evaluate indirectly the efficacy of elimination and containment strategies. MATERIAL AND METHODS: In 2009, 35 adults in a rural village in the Canton of Geneva were recruited. Data were collected by means of questionnaires and skin-prick tests were done on each participant. The study was approved by the local Ethics Committee. RESULTS: Based on questionnaires, 48.6% had rhinitis (95% confidence interval [CI] 32.9-64.4; n = 17/35) and 17.1% asthma (95% CI 8.1-32.6; n = 6/35). Atopy was diagnosed in 26.4% (95% CI 12.9-44.4) of the sample (n = 9/34). Ragweed sensitisation was found in 2.9% (95% CI 0.7-19.7; n = 1/34), mugwort sensitisation in 2.9% (95% CI 0.1-14.9; n = 1/35), alder sensitisation in 17.1% (95% CI 6.6-33.6; n = 6/35), ash sensitisation in 12.5% (95% CI 3.5-29.0; n = 4/32) and grass sensitisation in 22.9% (95% CI 10.4-40.1; n = 8/35). Ragweed (95% CI 0.1-14.9; n = 1/34) and mugwort allergies (95% CI 0.1-14.9; n = 1/35) were both found in 2.9% of the population. CONCLUSION: This study showed a surprisingly low incidence of ragweed sensitisation and allergy, of 2.9% and 2.9%, respectively, 20 years after the first ragweed detection in Geneva. The feared rise in ragweed allergy seems not to have happened in Switzerland, compared with other ragweed colonised countries. These results strongly support early field strategies against ragweed.