Summary
Background
IgE autoantibodies are considered to be involved in the pathogenesis of bullous pemphigoid (BP), particularly inflammatory and erythematous phenotypes.
Objectives
To develop ...reliable enzyme‐linked immunosorbent assays (ELISAs) for the detection of IgE autoantibodies to both BP180 and BP230 in BP sera, and to compare the ELISA results with clinical features.
Methods
We used commercially available IgG ELISAs to develop IgE ELISAs for both BP180 and BP230. To determine the influence of excess amounts of IgG autoantibodies, all normal and BP sera were tested before and after IgG adsorption. The results of the IgE ELISAs were statistically compared with various ELISAs and various clinical parameters, including our own severity scores and BP phenotypes.
Results
IgG adsorption generally showed no changes in sensitivity and specificity for IgE ELISAs, although slight cross‐reactivity of anti‐IgE secondary antibody to IgG and interference of excess amounts of IgG autoantibodies to IgE reactivity were suggested. IgE autoantibodies to BP180 were found in 21 of 36 BP sera and IgE autoantibodies to BP230 were found in 18 of 36 BP sera. The results of IgG and IgE ELISAs for both BP180 and BP230 were well correlated. IgG and IgE anti‐BP180 antibodies correlated with disease activity but IgG and IgE anti‐BP230 autoantibodies did not. IgE anti‐BP230 autoantibodies correlated with nodular phenotype but not erythematous phenotype.
Conclusions
The results of this study indicated that IgE autoantibodies to both BP180 and BP230 are frequently detected in BP sera. IgE anti‐BP180 autoantibodies seemed to be pathogenic, while an association between IgE autoantibodies and inflammatory BP phenotype was not indicated.
What's already known about this topic?
Although recent studies have indicated that IgE autoantibodies are frequently detected in bullous pemphigoid (BP), in addition to IgG autoantibodies, their diagnostic and pathogenic relevance have not been fully documented.
Reliable IgE enzyme‐linked immunosorbent assays (ELISAs) for BP antigens, particularly BP230, have not been established.
What does this study add?
This study establishes reliable diagnostic IgE ELISAs for both BP180 and BP230, in which the influence of excess amounts of IgG autoantibodies was extensively determined.
This study confirms the frequent detection of IgE autoantibodies to BP180 and BP230. IgE autoantibodies to BP180 correlated with disease activity, and IgE anti‐BP230 antibodies correlated with nodular phenotypes, while they were not correlated with the inflammatory erythematous phenotype.
What is the translational message?
We have developed reliable IgE ELISAs for both BP180 and BP230, which can be used in clinical practice.
This study suggests that titres of IgE anti‐BP180 autoantibodies correlated with disease activity in BP and should be clinically useful for selecting the best treatment, particularly with regard to anti‐IgE antibody therapy.
Linked Comment: Hammers and Payne. Br J Dermatol 2017; 177:13–14
Summary
Background
A subset of patients with bullous pemphigoid (BP) show deposition of IgE in the basement membrane zone (BMZ), yet the relationship between BMZ IgE and the clinical presentation of ...BP remains unclear.
Objectives
To investigate the relationship between IgE deposition, IgE levels in serum, and disease severity in patients with BP.
Methods
We investigated IgE autoantibodies in 53 patients with BP by direct immunofluorescence (DIF), indirect immunofluorescence and enzyme‐linked immunosorbent assay.
Results
Of 53 patients with BP, 23 (43%) had IgE deposition, 10 (19%) of whom were IgE+ and 13 (25%) IgE± according to DIF analyses. Erosion/blister (E/B) Bullous Pemphigoid Disease Area Index (BPDAI) scores were significantly higher in IgE+ patients than in IgE− patients (n = 15), while no significant differences were found for urticaria/erythema BPDAI scores. IgE+ and IgE± patients took longer to reduce their E/B BPDAI score by 75% after systemic corticosteroid treatment. BP180‐IgE levels were significantly higher among IgE+ patients than IgE± or IgE− patients (n = 10). Total IgE levels in the serum and blood eosinophil counts did not differ between IgE+, IgE± and IgE− patients. A significant correlation was detected between BP180‐IgG and BP180‐IgE, but not between BPDAI scores and any of BP180‐IgG, BP180‐IgE or blood eosinophil count.
Conclusions
IgE deposition in the BMZ is associated with higher E/B BPDAI scores and longer treatment periods. We conclude that IgE binding in the BMZ may contribute to BP pathogenesis by promoting blister formation.
What's already known about this topic?
BP180‐IgE autoantibodies have an important role in the pathogenesis of bullous pemphigoid (BP).
A subset of patients with BP display deposition of IgE within the basement membrane zone (BMZ) of skin tissue.
What does this study add?
Patients with in vivo IgE deposition in the BMZ displayed higher erosion/blister Bullous Pemphigoid Disease Area Index (BPDAI) scores, while urticaria/erythema BPDAI scores were not significantly different.
Patients with in vivo IgE deposition in the BMZ took longer to reduce their erosion/blister BPDAI score by 75% after systemic corticosteroid treatment.
BP180‐specific IgE levels in serum were higher among patients with linear IgE deposition in the BMZ than in those with granular or no IgE deposition.
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Summary
Background
Despite the established pathogenic role of anti‐desmoglein (Dsg) antibodies in classical pemphigus, the significance of autoantibodies to another desmosomal cadherin, desmocollin ...(Dsc) is at present unknown. No consistent immunoassay for immunoglobulin (Ig) G autoantibodies to Dscs has been developed.
Objectives
The aim of this study was to develop reliable assays to detect anti‐Dsc autoantibodies.
Methods
We expressed soluble recombinant proteins (RPs) of human Dsc1–3 in mammalian cells and examined sera of various types of pemphigus, including 79 paraneoplastic pemphigus (PNP) sera, by novel enzyme‐linked immunosorbent assays (ELISAs) using the RPs. We also performed ELISAs of Dsc baculoproteins and used the complementary DNA (cDNA) transfection method, and compared the results with those of mammalian ELISAs.
Results
Through mammalian ELISAs, IgG autoantibodies to Dsc1, Dsc2 and Dsc3 were detected in 16·5%, 36·7% and 59·5% of PNP sera, respectively, and considerable numbers of pemphigus herpetiformis (PH) and pemphigus vegetans (PVeg) sera reacted strongly with Dsc1 and Dsc3. Mammalian ELISAs were highly specific and more sensitive than baculoprotein ELISAs or the cDNA transfection method. Several Dsc‐positive sera, particularly PH sera, showed no reactivity with Dsgs. The reactivity of PNP serum and PVeg serum with Dscs was not abolished by pre‐absorption with Dsg RPs.
Conclusions
The results of these novel ELISAs indicated that IgG anti‐Dsc autoantibodies were frequently detected and potentially pathogenic in nonclassical pemphigus.
What's already known about this topic?
Despite the established pathogenic role of anti‐desmoglein (Dsg) antibodies in classical pemphigus, the significance of autoantibodies to another desmosomal cadherin, desmocollin (Dsc), is at present unknown.
No consistent immunoassay for IgG autoantibodies to Dscs has been developed.
What does this study add?
We have successfully established new sensitive and specific mammalian Dsc immunoglobulin (Ig) G enzyme‐linked immunosorbent assays.
Our data show that IgG anti‐Dsc autoantibodies are frequently detected and potentially pathogenic in particular types of nonclassical pemphigus.
ABSTRACT In the late stages of nuclear burning for massive stars (M > 8 M ), the production of neutrino-antineutrino pairs through various processes becomes the dominant stellar cooling mechanism. As ...the star evolves, the energy of these neutrinos increases and in the days preceding the supernova a significant fraction of emitted electron anti-neutrinos exceeds the energy threshold for inverse beta decay on free hydrogen. This is the golden channel for liquid scintillator detectors because the coincidence signature allows for significant reductions in background signals. We find that the kiloton-scale liquid scintillator detector KamLAND can detect these pre-supernova neutrinos from a star with a mass of 25 M at a distance less than 690 pc with 3 significance before the supernova. This limit is dependent on the neutrino mass ordering and background levels. KamLAND takes data continuously and can provide a supernova alert to the community.
Summary
Bullous pemphigoid (BP) is a rare skin disease that mainly affects people aged over 60. Patients develop red patches and blisters. BP is an autoimmune skin disease, meaning that antibodies – ...instead of attacking dangerous microorganisms as they are meant to – instead recognize and attach to molecules present in normal skin, causing an inflammatory reaction.
The two autoantigens (molecules) targeted by BP autoantibodies are BP180 and BP230, both of which are components of the basement membrane zone (BMZ, the junction between the outer and middle layers of skin).
In addition to autoantibodies called IgG, a subset of BP patients show deposition (presence) of a different antibody called IgE in the BMZ, yet the relationship between BMZ IgE and the severity of BP remains unclear.
In this study, from Japan, the authors investigated the relationship between IgE deposition in the BMZ, IgE levels in the blood serum, and disease severity in BP patients.
First, the authors examined skin samples of 53 bullous pemphigoid (BP) patients. 10 of them had strong, and 13 of them had weak IgE deposition in the BMZ. Next, of those 53 PB patients, the authors focused on 15 patients who had tested before treatment. Those who had strong IgE deposition on BMZ had more widespread BP than those who had no IgE deposition, as measured using a score called the bullous pemphigoid disease area index (PDAI).
Patients with strong or weak IgE deposition on BMZ took a longer time to improve after treatment with medicines called systemic corticosteroids started. In contrast, no significant differences were found for their Urticaria/Erythema BPDAI scores, which measure skin redness and hives, among other things.
These suggest that IgE deposition on BMZ influences the formation of blisters in BP patients. In line with previous work, the results indicate that anti‐IgE therapy such as omalizmab is effective for curing not only erythema (redness) and urticaria (hives) but also erosions and blisters in BP.
This is a summary of the study: Basement membrane zone IgE deposition is associated with bullous pemphigoid disease severity and treatment results.
Linked Article: Kamata et al. Br J Dermatol 2020; 182:1221–1227
Inner balloon production for KamLAND-Zen 800 Gando, A; Gando, Y; Hachiya, T ...
Journal of physics. Conference series,
02/2020, Letnik:
1468, Številka:
1
Journal Article, Conference Proceeding
Recenzirano
Odprti dostop
Abstract
KamLAND-Zen searches for neutrinoless double-beta decay with
136
Xe loaded liquid scintillator (LS). The LS container, a 25-
μ
m-thick clean nylon inner balloon is a key of the experiment ...since one of the main backgrounds in the ROI is
214
Bi from the inner balloon. In KamLAND-Zen 400 (operated from 2011 to 2015), dust contamination of the inner balloon from the environment limited the sensitivity, although the inner balloon was fabricated at a class-1 super clean room. We improved the production method of the inner balloon for KamLAND-Zen 800 (started DAQ in January, 2019) and successfully reduced the
214
Bi background level to one fifteenth as compared to the 2nd phase of KamLAND-Zen 400. The inner balloon film material and requirements, improved fabrication scheme, including establishment of clean environment and dust control, will be described.
We describe the details of a silicon–tungsten prototype electromagnetic calorimeter module and associated readout electronics. Detector performance for this prototype has been measured in test beam ...experiments at the CERN PS and SPS accelerator facilities in 2015/16. The results are compared to those in Monte Carlo Geant4 simulations. This is the first real-world demonstration of the performance of a custom ASIC designed for fast, lower-power, high-granularity applications.
ABSTRACT We present a search, using KamLAND, a kiloton-scale anti-neutrino detector, for low-energy anti-neutrino events that were coincident with the gravitational-wave (GW) events GW150914 and ...GW151226, and the candidate event LVT151012. We find no inverse beta-decay neutrino events within 500 s of either GW signal. This non-detection is used to constrain the electron anti-neutrino fluence and the total integrated luminosity of the astrophysical sources.
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