Endemic pemphigus foliaceus (fogo selvagem) and pemphigus vulgaris: immunoglobulin G heterogeneity detected by indirect immunofluorescence Pênfigo foliáceo endêmico (fogo selvagem) e pênfigo vulgar: heterogeneidade da imunoglobulina G detectada através da imunofluorescência indireta

Pemphigus are autoimmune intraepidermal blistering diseases in which immunoglobulin G (IgG) autoantibodies are directed against desmosomal glycoproteins. The aim of this study was to determine the IgG subclass profile of endemic pemphigus foliaceus (fogo selvagem) and pemphigus vulgaris utilizing indirect immunofluorescence. PATIENTS AND METHODS: Twenty-five patients with pemphigus vulgaris, 25 with endemic pemphigus foliaceus (fogo selvagem), and 25 healthy controls were analyzed by indirect immunofluorescence for circulating autoantibodies (total IgG and its subclasses). RESULTS: Our data revealed a significant correlation (P <.05) of disease activity and autoantibody levels in both forms of pemphigus, i.e., negative titers related to clinical remission, whereas positive results related to active disease. Immunoglobulin G subclass analysis in fogo selvagem demonstrated that in patients in remission, 56% showed positive immunoglobulin G4; in active disease, immunoglobulin G4 was the predominant subclass (100% positive in all cases). The IgG subclass profile in pemphigus vulgaris showed that in patients in remission, only 10% were positive for immunoglobulin G4; in active disease, positivity for immunoglobulin G4 was present in 78% to 88% of the cases. CONCLUSION: Subclass characterization of immunoglobulin G autoantibodies is a useful tool for pemphigus follow-up, since immunoglobulin G4 (IgG4) is the subclass that is closely related to recognition of pathogenic epitopes, and consequently with disease activity. Careful monitoring should be performed for fogo selvagem in clinical remission with a homogeneous IgG4 response, since this may indicate more frequent relapses.<br>Pênfigos são enfermidades auto-imunes bolhosas intraepidérmicas, onde auto-anticorpos IgG se dirigem contra glicoproteínas desmossomais. O objetivo deste estudo foi determinar o perfil de subclasses de imunoglubulina G no pênfigo foliáceo endêmico (fogo selvagem) e no pênfigo vulgar através da imunofluorescência indireta. MÉTODOS: Vinte e cinco doentes de pênfigo foliáceo endêmico (fogo selvagem), 25 de pênfigo vulgar e 25 controles sadios foram analisados através da imunofluorescência indireta, com respeito aos auto-anticorpos circulantes (imunoglobulina G total e subclasses). RESULTADOS: Nossos dados mostram uma correlação estatisticamente significativa (p<0.05) entre atividade da doença e títulos de auto-anticorpos circulantes em ambas as formas de pênfigo, ou seja, títulos negativos relacionaram-se com remissão clínica, enquanto resultados positivos correlacionaram-se com doença em atividade. A análise de subclasses de IgG mostrou que 56% dos doentes de fogo selvagem em remissão apresentaram apenas IgG4 positiva; na doença ativa, IgG4 foi a subclasse predominante, sendo positiva em 100% dos casos. Nos doentes de pênfigo vulgar, apenas 10% dos doentes em remissão apresentaram positividade exclusiva para IgG4; na doença em atividade, IgG4 esteve presente em 78-83,3% dos casos. CONCLUSÕES: A caracterização de subclasses de imunoglobulina G consiste em um instrumento de grande valia no seguimento de doentes de pênfigo, uma vez que a IgG4 é a subclasse intimamente relacionada com o reconhecimento de epítopos patogênicos, e consequentemente com atividade da enfermidade. No fogo selvagem em remissão com uma resposta homogênea 'as custas de IgG4, uma monitoração cuidadosa deve ser realizada, uma vez que isto pode significar uma maior chance de reativação

Long-lived coupled peeling ballooning modes preceding ELMs on JET

In some JET discharges, type-I edge localised modes (ELMs) are preceded by a class of low-frequency oscillations (Perez et al 2004 Nucl. Fusion 44 609). While in many cases the ELM is triggered during the growth phase of this oscillation, it is also observed that this type of oscillation can saturate and last for several tens of ms until an ELM occurs. In order to identify the nature of these modes, a wide pre-ELM oscillation database, including detailed pedestal profile information, has been assembled and analysed in terms of MHD stability parameters. The existence domain of these pre-ELM oscillations and the statistical distribution of toroidal mode numbers (n) up to n = 16 have been mapped in ballooning alpha (alpha(ball)) and either edge current density (J(edge)) or pedestal collisionality (nu(ee,ped)*) coordinates and compared to linear MHD stability predictions. The pre-ELM oscillations are reliably observed when the J/alpha ratio is high enough for the pedestal to access the coupled peeling-ballooning (PB) domain (aka stability nose). Conversely, when the pedestal is found to be in or near the high-n ballooning domain (which is at low J/alpha ratio), ELMs are usually triggered promptly, i.e. with no detectable pre-ELM oscillations, or with pre-ELM oscillations only observable on ECE whose n appears to be too high to be resolved by the magnetics. Individual discharges can sometimes exhibit a fairly wide range of pre-ELM mode numbers, but for a wider database, the statistical n-number domains are found to be well ordered along the J - alpha stability boundary and behave as expected from PB theory: the higher the J/alpha ratio, the lower the mode's measured n tends to be. Within the measurement uncertainties, the measured n is usually found to be compatible with the most unstable n predicted by the linear stability code MISHKA1. These results confirm the earlier hypothesis that these modes are coupled peeling-ballooning modes, and extend and generalise to higher-mode numbers the work by Huysmans et al (1998 Nucl. Fusion 38 179), who identified the lowest n modes as pure external kink modes. Since the destabilisation of PB modes is widely accepted to give rise to ELMs, the mode saturation and delayed ELM triggering that is sometimes observed is rather unexpected. Possibilities to reconcile the extended lifetime of these modes with current ELM models are briefly discussed, but will require further investigation

Overview of JET results for optimising ITER operation

The JET 2019-2020 scientific and technological programme exploited the results of years of concerted scientific and engineering work, including the ITER-like wall (ILW: Be wall and W divertor) installed in 2010, improved diagnostic capabilities now fully available, a major neutral beam injection upgrade providing record power in 2019-2020, and tested the technical and procedural preparation for safe operation with tritium. Research along three complementary axes yielded a wealth of new results. Firstly, the JET plasma programme delivered scenarios suitable for high fusion power and alpha particle (alpha) physics in the coming D-T campaign (DTE2), with record sustained neutron rates, as well as plasmas for clarifying the impact of isotope mass on plasma core, edge and plasma-wall interactions, and for ITER pre-fusion power operation. The efficacy of the newly installed shattered pellet injector for mitigating disruption forces and runaway electrons was demonstrated. Secondly, research on the consequences of long-term exposure to JET-ILW plasma was completed, with emphasis on wall damage and fuel retention, and with analyses of wall materials and dust particles that will help validate assumptions and codes for design and operation of ITER and DEMO. Thirdly, the nuclear technology programme aiming to deliver maximum technological return from operations in D, T and D-T benefited from the highest D-D neutron yield in years, securing results for validating radiation transport and activation codes, and nuclear data for ITER