Role of environmental factors in autoantibody production-importance of a detailed analysis in a small cohort

In the previous issue of Arthritis Research & Therapy, Muro and colleagues reported a detailed epidemiologic analysis in central Japan on one of the new myositis-specific autoantibodies to MDA-5 (melanoma differentiation-associated gene 5), which is associated with clinically amyopathic dermatomyositis accompanying interstitial lung disease. The increasing prevalence of anti-MDA-5, higher prevalence in small rural towns, and geographical clustering in two areas along the Kiso River suggest a role of environmental factors associated with rural communities or the river/water system or both. A detailed analysis of a small cohort may offer clues, which is ignored in multi-center studies, to the pathogenesis of systemic rheumatic diseases and autoantibody production. \ua9 2012 BioMed Central Ltd

MicroRNAs in rheumatoid arthritis

Rheumatoid arthritis (RA) is a chronic and severe autoimmune disease that affects joint tissues, bone, and cartilage. However, the pathogenesis of RA is still unclear. Autoantibodies such as rheumatoid factor and anti-cyclic citrullinated peptide are useful tools for early diagnosis, monitoring disease activity, and predicting prognosis. Recently, many groups have focused their attention on the role of microRNAs in the pathogenesis of RA, as well as a potential biomarker to monitor RA. In fact, the expression of some microRNAs, such as miR-146a, is upregulated in different cell types and tissues in RA patients. MicroRNAs in RA could also be considered as possible future targets for new therapeutic approaches. \ua9 2011 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved

Rpp25 is a major target of autoantibodies to the Th/To complex as measured by a novel chemiluminescent assay

Introduction: Autoantibodies to the Th/To antigen have been described in systemic sclerosis (SSc) and several proteins of the macromolecular Th/To complex have been reported to react with anti-Th/To antibodies. However, anti-Th/To has not been clinically utilized due to unavailability of commercial tests. The objective of the present study is to evaluate the newly developed ELISA and chemiluminescent immunoassay (CLIA) to measure autoantibodies to Rpp25 (a component of the Th/To complex) using immunoprecipitation (IP) as the reference method.Methods: The first cohort consisted of 123 SSc patients including 7 anti-Th/To positive samples confirmed by IP. Additional seven anti-Th/To positive samples from non-SSc patients were also tested. For evaluation of the QUANTA Flash Rpp25 CLIA (research use only), 8 anti-Th/To IP positives, a cohort of 70 unselected SSc patients and sera from various disease controls (n = 357) and random healthy individuals (n = 10) were studied.Results: Anti-Rpp25 antibodies determined by ELISA were found in 11/14 anti-Th/To IP positive but only in 1/156 (0.6%) negative samples resulting in a positive percent agreement of 78.6% (95% confidence interval [CI] 49.2, 95.3%) and a negative percent agreement of 99.4% (95% CI 96.4, 100.0%). To verify the results using a second method, 53 samples were tested by ELISA and CLIA for anti-Rpp25 reactivity and the results were highly correlated (rho = 0.71, 95% CI 0.56, 0.81; P < 0.0001). To define the cutoff of the CLIA, anti-Th/To IP positive and negative sera were tested using the anti-Rpp25 CLIA. At the cutoff selected by receiver operating characteristic (ROC) analysis 8/8 (100.0%) of the anti-Th/To positive sera but only 2/367 (0.5%) of the controls were positive for anti-Rpp25 antibodies. The positive and negative percent agreements were 100.0% (95% CI 63.1, 100.0%) and 99.5% (95% CI 98.0, 99.9%), respectively. In the disease cohorts 2/70 (2.9%) of the SSc patients were positive for anti-Rpp25 antibodies compared to 2/367 (0.5%) of the controls (P = 0.032). ROC analysis showed discrimination between SSc patients and controls with an area under the curve value of 0.732 (95% CI 0.655, 0.809).Conclusion: Rpp25 is a major target of autoantibodies to the Th/To autoantigen complex. Further studies are needed to evaluate the clinical utility of the new assays. \ua9 2013 Mahler et al.; licensee BioMed Central Ltd

MicroRNA-146a in autoimmunity and innate immune responses

MicroRNA (miRNA) are approximately 22 nucleotide single-stranded RNA that regulate the stability of target messenger RNA by selective binding to specific sites at the 30-untranslated regions (UTR). This triggers repression in translation and mRNA degradation. It has been estimated that approximately 60% of all mRNA are under the control of miRNA. Among the known hundreds of miRNA, some are considered master regulators controlling either a single or multiple cellular pathways. Some miRNA are known to affect development and cell differentiation, while others are implicated in immunity and autoimmune diseases. A very interesting example is miR-146a, which has been reported to be downregulated in systemic lupus erythematosus and upregulated in rheumatoid arthritis (RA). Several groups have recently focused their attention on miRNA in the pathogenesis of RA. Interestingly, the expression of miR-146a is upregulated in different cell types and tissues in RA patients. miRNA in RA could also be considered as possible future targets for new therapeutic approaches. This discussion will focus on the current understanding in the function of miR-146a in endotoxin tolerance and cross-tolerance, and how it may contribute to modulate the overproduction of known pathogenic cytokines, such as tumour necrosis factor \u3b1

Multiscale approach optimization on surface wettability change on rough surface

Surface wettability is known that is not only governed by chemical structure but also by the surface geometrical structure. A multiscale approach on rough surface wettability study was presented in this paper. The wettability study of photo-switched trans and cis isomers of azobenzene on different substrates was first calculated by molecular dynamics calculations. Different chemical structures and configurations were input into the molecular model to get equilibrated structures. Contact angle is then estimated and input into finite element model with roughness factor included. The parameters were input into the FLUENT software to estimate the respective surface wettability for each individual trans and cis configuration on different rough surface. The simulated wettability results were found to be in good correlation with experimental measures. This multiscale approach provides an opportunity to study the combined effects of surface interaction at molecular scale, and micron scale surface roughness, on the wettability of a rough surface. It enables the prediction of contact angle of liquid media on rough surfaces which will be a powerful tool in the selection and optimization of material and substrate surface structure to control the hydrophobicity/hydrophilicity at liquid/solid interface. ©2010 IEEE

UV-activated surface modification of photo-cleavage polymer for contact printing applications

Polymer electronics is an emerging technology for the last decade. For cost-efficient mass production and for thin, flexible polymer electronic systems, large area patterning processes may be an interesting option as an economic production method and will potentially play an important role in polymer electronics manufacturing. High resolution patterning methods for defining the separation between electrodes in electronic devices are important in manufacturing. The control of surface wettability during contact printing is an interesting approach because of its wide variety of applications. Stimuli-responsive surfaces make it possible to control the wettability of the surface and have been demonstrated by various methods, including UV light-irradiation. Herein, a new strategy was demonstrated using free radical initiator to induce mold release between PDMS mold and the resins under UV irradiation. For example, by applying a thin layer of benzoyl peroxide (BPO) on PDMS surface, an increase of contact angle is achieved after UV irradiation. This method can be used as a transfer mechanism from mold to substrate. It was noticed that sufficient time of BPO deposition for the PDMS mold surface treatment is required for this strategy. Optimum concentration of BPO and suitable solvent system are concerns in the effectiveness of surface treatment. From this study, some preliminary insight in studying the controlling factors for the UV activation of free radicals on PDMS surface was shown. It can be shown that the molecular structure, polarity of materials, UV sensitivity of the free radical initiators, and solvent used, have direct effect on the efficiency of the wettability change under the UV irradiation. By knowing the controlling factors of UV assisted stimuli responses, printing can be improved and be applied in many other cases. © 2008 IEEE

Autoantibodies to Argonaute 2 (Su antigen)

Like many other classical autoantibodies in systemic rheumatic diseases, anti-Su antibodies were originally defined by the double immunodiffusion assay in the early 80s. However, despite its high prevalence, only a few reports on anti-Su were published in the following years and the progress in characterizing the target antigens and clinical significance was slow, probably due to its inconsistent or poor reactivity in other standard immunoassays. In 2006 the target antigen was identified as the microRNA (miRNA)-binding protein Argonaute 2 (Ago2). Ago2 is a key component of the RNA-induced silencing complex enriched in cytoplasmic foci called GW bodies. Due to preferential reactivity of human autoantibodies with native antigens, immunoprecipitation is the only method to reliably detect anti-Su/Ago2 antibodies. Anti-Su/Ago2 does not appear to have disease specificity since it is found in 10-20% of patients with various rheumatic diseases, including systemic lupus erythematosus, scleroderma, polymyositis/dermatomyositis, and Sj\uf6gren's syndrome, as well as apparently healthy individuals at lower prevalence. The clinical significance and the mechanism of production of anti-Su/Ago2 remains to be clarified

Autoantibodies to argonaute 2 (su antigen)

Like many other classical autoantibodies in systemic rheumatic diseases, anti-Su antibodies were originally defined by the double immunodiffusion assay in the early 80s. However, despite its high prevalence, only a few reports on anti-Su were published in the following years and the progress in characterizing the target antigens and clinical significance was slow, probably due to its inconsistent or poor reactivity in other standard immunoassays. In 2006 the target antigen was identified as the microRNA (miRNA)-binding protein Argonaute 2 (Ago2). Ago2 is a key component of the RNA-induced silencing complex enriched in cytoplasmic foci called GW bodies. Due to preferential reactivity of human autoantibodies with native antigens, immunoprecipitation is the only method to reliably detect anti-Su/Ago2 antibodies. Anti-Su/Ago2 does not appear to have disease specificity since it is found in 10-20% of patients with various rheumatic diseases, including systemic lupus erythematosus, scleroderma, polymyositis/dermatomyositis, and Sjögren's syndrome, as well as apparently healthy individuals at lower prevalence. The clinical significance and the mechanism of production of anti-Su/Ago2 remains to be clarified. Zapotitlán Springer Science+Business Media New York 2013

From autoantibody research to standardized diagnostic assays in the management of humen diseases : Report on the 12th Dresden Symposium on Autoantibodies September 23–26, 2015

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