Antibody to Aquaporin 4 in the Diagnosis of Neuromyelitis Optica

BACKGROUND: Neuromyelitis optica (NMO) is a demyelinating disease of the central nervous system (CNS) of putative autoimmune aetiology. Early discrimination between multiple sclerosis (MS) and NMO is important, as optimum treatment for both diseases may differ considerably. Recently, using indirect immunofluorescence analysis, a new serum autoantibody (NMO-IgG) has been detected in NMO patients. The binding sites of this autoantibody were reported to colocalize with aquaporin 4 (AQP4) water channels. Thus we hypothesized that AQP4 antibodies in fact characterize NMO patients. METHODS AND FINDINGS: Based on these observations we cloned human water channel AQP4, expressed the protein in a eukaryotic transcription/translation system, and employed the recombinant AQP4 to establish a new radioimmunoprecipitation assay (RIPA). Indeed, application of this RIPA showed that antibodies against AQP4 exist in the majority of patients with NMO (n = 37; 21 positive) as well as in patients with isolated longitudinally extensive transverse myelitis (n = 6; six positive), corresponding to a sensitivity of 62.8% and a specificity of 98.3%. By contrast, AQP4 antibodies were virtually absent in 291 other participants, which included patients with MS (n = 144; four positive), patients with other inflammatory and noninflammatory neurological diseases (n = 73; one positive), patients with systemic autoimmune diseases (n = 45; 0 positive), and healthy participants (n = 29; 0 positive). CONCLUSIONS: In the largest series reported so far to our knowledge, we quantified AQP4 antibodies in patients with NMO versus various other diseases, and showed that the aquaporin 4 water channel is a target antigen in a majority of patients with NMO. The newly developed assay represents a highly specific, observer-independent, and easily reproducible detection method facilitating clinically relevant discrimination between NMO, MS, and other inflammatory diseases

Biochar organic fertilizers from natural resources as substitute for mineral fertilizers

International audienceBiochars are new, carbon-rich materials that could sequester carbon in soils improve soil properties and agronomic performance, inspired by investigations of Terra Preta in Amazonia. However, recent studies showed contrasting performance of biochar. In most studies, only pure biochar was used in tropical environments. Actually, there is little knowledge on the performance of biochar in combination with fertilizers under temperate climate. Therefore, we conducted an experiment under field conditions on a sandy Cambisol near Gorleben in Northern Germany. Ten different treatments were established in 72-m2 plots and fivefold field replicates. Treatments included mineral fertilizer, biogas digestate, microbially inoculated biogas digestate and compost either alone or in combination with 1 to 40 Mg ha−1 of biochar. Soil samples were taken after fertilizer application and maize harvest. Our results show that the biochar addition of 1 Mg ha−1 to mineral fertilizer increased maize yield by 20 %, and biochar addition to biogas digestate increased maize yield by 30 % in comparison to the corresponding fertilizers without biochar. The addition of 10 Mg ha−1 biochar to compost increased maize yield by 26 % compared to pure compost. The addition of 40 Mg ha−1 biochar to biogas digestate increased maize yield by 42 % but reduced maize yield by 50 % when biogas digestate was fermented together with biochar. Biochar-fertilizer combinations increased K, Mg and Zn and reduced Na, Cu, Ni and Cd uptake into maize. Overall, our findings demonstrate that biochar-fertilizer combinations have a better performance than pure fertilizers, in terms of yield and plant nutrition. Therefore, an immediate substitution of mineral fertilizers is possible to close regional nutrient cycles

The dermatomyositis-specific autoantigen Mi2 is a component of a complex containing histone deacetylase and nucleosome remodeling activities.

Histone acetylation and deacetylation were found to be catalyzed by structurally distinct, multisubunit complexes that mediate, respectively, activation and repression of transcription. ATP-dependent nucleosome remodeling, mediated by different multisubunit complexes, was thought to be involved only in transcription activation. Here we report the isolation of a protein complex that contains both histone deacetylation and ATP-dependent nucleosome remodeling activities. The complex contains the histone deacetylases HDAC1/2, histone-binding proteins, the dermatomyositis-specific autoantigen Mi2beta, a polypeptide related to the metastasis-associated protein 1, and a novel polypeptide of 32 kDa. Patients with dermatomyositis have a high rate of malignancy. The finding that Mi2beta exists in a complex containing histone deacetylase and nucleosome remodeling activities suggests a role for chromatin reorganization in cancer metastasis

Antibody Ratios Found in Patients with NMO and in Patients with Relevant Differential Diagnoses or Healthy Controls

<p>Each individual value represents the result from a single serum sample tested twice with the AQP4 RIPA. Black horizontal bars represent mean. The dashed horizontal line indicates the cutoff at an antibody ratio of 11. Diagnostic categories: NMO, neuromyelitis optica; LETM longitudinally extensive transverse myelitis; MS/ON+, multiple sclerosis with optic neuritis; MS/ON−, multiple sclerosis without optic neuritis; ON, optic neuritis; MYL, myelitis extending over fewer than three vertebral segments on MRI; OIND, other inflammatory neurological disorders and systemic disorders with neurological involvement (e.g., neuroborreliosis, chronic inflammatory demyelinating polyneuropathy; for exact classification see legend for <a href="http://www.plosmedicine.org/article/info:doi/10.1371/journal.pmed.0040133#pmed-0040133-t001" target="_blank">Table 1</a>); OND, other noninflammatory neurological diseases (e.g., carpal tunnel syndrome); RD, rheumatological diseases without neurological involvement (for exact classification see legend for <a href="http://www.plosmedicine.org/article/info:doi/10.1371/journal.pmed.0040133#pmed-0040133-t001" target="_blank">Table 1</a>); HC, healthy controls.</p