Common denominators in the immunobiology of IgG4 autoimmune diseases: What do glomerulonephritis, pemphigus vulgaris, myasthenia gravis, thrombotic thrombocytopenic purpura and autoimmune encephalitis have in common?

IgG4 autoimmune diseases (IgG4-AID) are an emerging group of autoimmune diseases that are caused by pathogenic autoantibodies of the IgG4 subclass. It has only recently been appreciated, that members of this group share relevant immunobiological and therapeutic aspects even though different antigens, tissues and organs are affected: glomerulonephritis (kidney), pemphigus vulgaris (skin), thrombotic thrombocytopenic purpura (hematologic system) muscle-specific kinase (MuSK) in myasthenia gravis (peripheral nervous system) and autoimmune encephalitis (central nervous system) to give some examples. In all these diseases, patients’ IgG4 subclass autoantibodies block protein-protein interactions instead of causing complement mediated tissue injury, patients respond favorably to rituximab and share a genetic predisposition: at least five HLA class II genes have been reported in individual studies to be associated with several different IgG4-AID. This suggests a role for the HLA class II region and specifically the DRβ1 chain for aberrant priming of autoreactive T-cells toward a chronic immune response skewed toward the production of IgG4 subclass autoantibodies. The aim of this review is to provide an update on findings arguing for a common pathogenic mechanism in IgG4-AID in general and to provide hypotheses about the role of distinct HLA haplotypes, T-cells and cytokines in IgG4-AID

Exploring the effect of vitamin D₃ supplementation on the anti-EBV antibody response in relapsing-remitting multiple sclerosis.

Epstein-Barr virus (EBV) infection and vitamin D insufficiency are potentially interacting risk factors for multiple sclerosis (MS). To investigate the effect of high-dose vitamin D <sub>3</sub> supplements on antibody levels against the EBV nuclear antigen-1 (EBNA-1) in patients with relapsing-remitting multiple sclerosis (RRMS) and to explore any underlying mechanism affecting anti-EBNA-1 antibody levels. This study utilized blood samples from a randomized controlled trial in RRMS patients receiving either vitamin D <sub>3</sub> (14,000 IU/day; n = 30) or placebo ( n = 23) over 48 weeks. Circulating levels of 25-hydroxyvitamin-D, and anti-EBNA-1, anti-EBV viral capsid antigen (VCA), and anti-cytomegalovirus (CMV) antibodies were measured. EBV load in leukocytes, EBV-specific cytotoxic T-cell responses, and anti-EBNA-1 antibody production in vitro were also explored. The median antibody levels against EBNA-1, but not VCA and CMV, significantly reduced in the vitamin D <sub>3</sub> group (526 (368-1683) to 455 (380-1148) U/mL) compared to the placebo group (432 (351-1280) to 429 (297-1290) U/mL; p = 0.023). EBV load and cytotoxic T-cell responses were unaffected. Anti-EBNA-1 antibody levels remained below detection limits in B-cell cultures. High-dose vitamin D <sub>3</sub> supplementation selectively reduces anti-EBNA-1 antibody levels in RRMS patients. Our exploratory studies do not implicate a promoted immune response against EBV as the underlying mechanism

Detection Methods for Autoantibodies in Suspected Autoimmune Encephalitis

This review provides an overview on different antibody test methods that can be applied in cases of suspected paraneoplastic neurological syndromes (PNS) and anti-neuronal autoimmune encephalitis (AIE) in order to explain their diagnostic value, describe potential pitfalls and limitations, and discuss novel approaches aimed at discovering further autoantibodies. Onconeuronal antibodies are well-established biomarkers for PNS and may serve as specific tumor markers. The recommended procedure to detect onconeuronal antibodies is a combination of indirect immunohistochemistry on fixed rodent cerebellum and confirmation of the specificity by line assays. Simplification of this approach by only using line assays with recombinant proteins bears the risk to miss antibody-positive samples. Anti-neuronal surface antibodies are sensitive and specific biomarkers for AIE. Their identification requires the use of test methods that allow the recognition of conformation dependent epitopes. These commonly include cell-based assays and tissue based assays with unfixed rodent brain tissue. Tissue based assays can detect most of the currently known neuronal surface antibodies and thus enable broad screening of biological samples. A complementary testing on live neuronal cell cultures may confirm that the antibody recognizes a surface epitope. In patients with peripheral neuropathy, the screening may be expanded to teased nerve fibers to identify antibodies against the node of Ranvier. This method helps to identify a novel subgroup of peripheral autoimmune neuropathies, resulting in improved immunotherapy of these patients. Tissue based assays are useful to discover additional autoantibody targets that play a role in diverse autoimmune neurological syndromes. Antibody screening assays represent promising avenues of research to improve the diagnostic yield of current assays for antibody-associated autoimmune encephalitis

Complex Risks from Old Urban Waste Landfills: Sustainability Perspective from Iasi, Romania

Landfills continue to represent the most frequent managerial practice for municipal solid wastes and an increasing and complex problem globally. In certain countries, a transition to an open society and free market is superimposed on the transition to sustainability, resulting in even higher complexity of management. This paper proposes an approach for problem-structuring of landfills in complex transitions: sustainability or unsustainability of a management approach is determined by a set of sustainability filters that are defined by sets of indicators and prioritized according the systemic concept of sustainability, which says that economy is embedded in society, which is embedded in nature. The writers exercise this approach with an old landfill in Iasi, Romania, and conclude for unsustainability, because the ecological sustainability filter is not successfully passed. Social and economic sustainability filters are also discussed in relation with the ecological sustainability indicators. The described approach allows a coherent, transdisciplinary synthesis of knowledge scattered across various disciplines, a pervasive problem in landfill management. The case study helps distinguish between generally true and context-dependent aspects.Peer reviewe

Regeneracja roslin trzech genotypow lubinu waskolistnego z niedojrzalych osi zarodkowych

Przeprowadzono regenerację roślin trzech genotypów łubinu wąskolistnego z wyszczepianych osi zarodkowych niedojrzałych nasion. Zastosowano cztery pożywki zawierające makroelementy z pożywki MS, czterokrotne stężenie mikroelementów z MS, witaminy z pożywki B5, dodatek 1,38 g/L L-proliny, 30 g/L sacharozy i 7 g/L agaru. Każda pożywka zawierała inną kombinację zawartości BA i NAA. Najwięcej pędów tworzył genotyp 410 - średnio 3,2 na eksplantat. Najlepszą pożywką indukującą była pożywka S2 zawierająca 3,0 mg/L BA i 0,4 mg/L NAA.Plant regeneration of three blue lupin (Lupinus angustifolius L.) genotypes on embryonic axes taken from immature seeds was carried out. Four media containing macroelements of MS medium, fourfold concentration of microelements of MS, vitamins of B5 medium and supplement of 1,38 g/L L-proline, 30 g/L saccharose and 7 g/L agar were used. Each of medium contained different combination of BA and NAA content. The highest number of shoots were obtained on 410 genotype - average 3,2 per explant. The best inducing was S2 medium containing 3,0 mg/L of BA and 0,4 mg/L of NAA