Argonaute Autoantibodies as Biomarkers in Autoimmune Neurologic Diseases

OBJECTIVE: To identify and characterize autoantibodies (Abs) as novel biomarkers for an autoimmune context in patients with central and peripheral neurologic diseases. METHODS: Two distinct approaches (immunoprecipitation/mass spectrometry-based proteomics and protein microarrays) and patients' sera and CSF were used. The specificity of the identified target was confirmed by cell-based assay (CBA) in 856 control samples. RESULTS: Using the 2 methods as well as sera and CSF of patients with central and peripheral neurologic involvement, we identified Abs against the family of Argonaute proteins (mainly AGO1 and AGO2), which were already reported in systemic autoimmunity. AGO-Abs were mostly of immunoglobulin G 1 subclass and conformation dependent. Using CBA, AGO-Abs were detected in 21 patients with a high suspicion of autoimmune neurologic diseases (71.4% were women; median age 57 years) and only in 4/856 (0.5%) controls analyzed by CBA (1 diagnosed with small-cell lung cancer and the other 3 with Sjögren syndrome). Among the 21 neurologic patients identified, the main clinical presentations were sensory neuronopathy (8/21, 38.1%) and limbic encephalitis (6/21, 28.6%). Fourteen patients (66.7%) had autoimmune comorbidities and/or co-occurring Abs, whereas AGO-Abs were the only autoimmune biomarker for the remaining 7/21 (33.3%). Thirteen (61.9%) patients were treated with immunotherapy; 8/13 (61.5%) improved, and 3/13 (23.1%) remained stable, suggesting an efficacy of these treatments. CONCLUSIONS: AGO-Abs might be potential biomarkers of autoimmunity in patients with central and peripheral nonparaneoplastic neurologic diseases. In 7 patients, AGO-Abs were the only biomarkers; thus, their identification may be useful to suspect the autoimmune character of the neurologic disorder. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that AGO-Abs are more frequent in patients with autoimmune neurologic diseases than controls

Diffuse panbronchiolitis: not just an Asian disease: Australian case series and review of the literature

Diffuse panbronchiolitis is a disease of obscure aetiology that is traditionally associated with Asian ethnicity. We propose that this disease also occurs in Caucasians and the incidence in this population is greater than currently recognised. We further propose that high resolution computed tomography (HRCT) and response to macrolide therapy should be relied upon to make this diagnosis without verification by lung biopsy. In most circumstances, obtaining a biopsy for histopathology is not practical, and the disease may then be mistaken for other more common airway diseases. Accuracy of diagnosis is important as untreated disease is associated with a poor prognosis, and effective treatment is available. We report four out of a series of cases as evidence that DPB is in fact more common in the Western population than is currently understood

Emulsion sheet doublets as interface trackers for the OPERA experiment

New methods for efficient and unambiguous interconnection between electronic counters and target units based on nuclear photographic emulsion films have been developed. The application to the OPERA experiment, that aims at detecting oscillations between mu neutrino and tau neutrino in the CNGS neutrino beam, is reported in this paper. In order to reduce background due to latent tracks collected before installation in the detector, on-site large-scale treatments of the emulsions ("refreshing") have been applied. Changeable Sheet (CSd) packages, each made of a doublet of emulsion films, have been designed, assembled and coupled to the OPERA target units ("ECC bricks"). A device has been built to print X-ray spots for accurate interconnection both within the CSd and between the CSd and the related ECC brick. Sample emulsion films have been extensively scanned with state-of-the-art automated optical microscopes. Efficient track-matching and powerful background rejection have been achieved in tests with electronically tagged penetrating muons. Further improvement of in-doublet film alignment was obtained by matching the pattern of low-energy electron tracks. The commissioning of the overall OPERA alignment procedure is in progress.Comment: 19 pages, 19 figure

Evaluation of chloroform/methanol extraction to facilitate the study of membrane proteins of non-model plants

Membrane proteins are of great interest to plant physiologists because of their important function in many physiological processes. However, their study is hampered by their low abundance and poor solubility in aqueous buffers. Proteomics studies of non-model plants are generally restricted to gel-based methods. Unfortunately, all gel-based techniques for membrane proteomics lack resolving power. Therefore, a very stringent enrichment method is needed before protein separation. In this study, protein extraction in a mixture of chloroform and methanol in combination with gel electrophoresis is evaluated as a method to study membrane proteins in non-model plants. Benefits as well as disadvantages of the method are discussed. To demonstrate the pitfalls of working with non-model plants and to give a proof of principle, the method was first applied to whole leaves of the model plant Arabidopsis. Subsequently, a comparison with proteins extracted from leaves of the non-model plant, banana, was made. To estimate the tissue and organelle specificity of the method, it was also applied on banana meristems. Abundant membrane or lipid-associated proteins could be identified in both tissues, with the leaf extract yielding a higher number of membrane proteins

Novel event classification based on spectral analysis of scintillation waveforms in Double Chooz

Liquid scintillators are a common choice for neutrino physics experiments, but their capabilities to perform background rejection by scintillation pulse shape discrimination is generally limited in large detectors. This paper describes a novel approach for a pulse shape based event classification developed in the context of the Double Chooz reactor antineutrino experiment. Unlike previous implementations, this method uses the Fourier power spectra of the scintillation pulse shapes to obtain event-wise information. A classification variable built from spectral information was able to achieve an unprecedented performance, despite the lack of optimization at the detector design level. Several examples of event classification are provided, ranging from differentiation between the detector volumes and an efficient rejection of instrumental light noise, to some sensitivity to the particle type, such as stopping muons, ortho-positronium formation, alpha particles as well as electrons and positrons. In combination with other techniques the method is expected to allow for a versatile and more efficient background rejection in the future, especially if detector optimization is taken into account at the design level

Study of the effects induced by lead on the emulsion films of the OPERA experiment

The OPERA neutrino oscillation experiment is based on the use of the Emulsion Cloud Chamber (ECC). In the OPERA ECC, nuclear emulsion films acting as very high precision tracking detectors are interleaved with lead plates providing a massive target for neutrino interactions. We report on studies related to the effects occurring from the contact between emulsion and lead. A low radioactivity lead is required in order to minimize the number of background tracks in emulsions and to achieve the required performance in the reconstruction of neutrino events. It was observed that adding other chemical elements to the lead, in order to improve the mechanical properties, may significantly increase the level of radioactivity on the emulsions. A detailed study was made in order to choose a lead alloy with good mechanical properties and an appropriate packing technique so as to have a low enough effective radioactivity.Comment: 19 pages, 11 figure

Implications of the polymorphism of HLA-G on its function, regulation, evolution and disease association

The HLA-G gene displays several peculiarities that are distinct from those of classical HLA class I genes. The unique structure of the HLA-G molecule permits a restricted peptide presentation and allows the modulation of the cells of the immune system. Although polymorphic sites may potentially influence all biological functions of HLA-G, those present at the promoter and 3′ untranslated regions have been particularly studied in experimental and pathological conditions. The relatively low polymorphism observed in the MHC-G coding region both in humans and apes may represent a strong selective pressure for invariance, whereas, in regulatory regions several lines of evidence support the role of balancing selection. Since HLA-G has immunomodulatory properties, the understanding of gene regulation and the role of polymorphic sites on gene function may permit an individualized approach for the future use of HLA-G for therapeutic purposes