Characterization Of Anti-dna Autoantibody Responses From Lymphoid Cells Of Normal Human Origin

Spontaneous and pokeweed mitogen (PWM) induced anti-nucleic acid antibodies were assayed in cultures of tonsillar and peripheral blood lymphocytes (PBLs) of healthy donors as well as in PBLs from systemic lupus erythematosus (SLE) patients. IgM antibodies (Abs) to single stranded DNA (ssDNA) were detected frequently in PWM cultures of both SLE PBLs (88%) and normal tonsillar lymphocytes (78%). IgM and IgG anti-double stranded DNA Abs were found at high frequencies of 73% and 59% respectively with PWM stimulated SLE PBLs.;Spontaneous production of IgM Abs to ssDNA was identical (44%) in normal tonsillar lymphocytes and PBLs of SLE patients. Human:human hybridomas were generated by fusion of normal tonsillar lymphocytes with GM 4672 cell line. 11.8% of these hybridomas secreted IgM anti-nucleic acid Abs. These monoclonal antibodies (mAbs) reacted with ssDNA, DNA polydG{dollar}\cdot{dollar}polydC, poly-(dA-dT), low molecular weight DNA, RNA and cardiolipin.;Four of the ten mAbs studied reacted with vimentin as well. Anti-idiotypic Ab raised against one of the anti-nucleic acid mAb, was utilized to examine the expression of the corresponding idiotype (ID), 4.6.3, in the panel of hybridoma cell lines as well as in sera of normals and SLE patients. The 4.6.3. ID framework determinant was expressed by a third of all nucleic acid-reactive and non-nucleic acid-reactive mAbs and it was detected in sera from 90% of SLE patients and 24% of normals.;The level of 4.6.3 ID in patients was independent of total serum IgM and IgG and of serum anti-nucleic acid Ab concentrations. These data indicate convincingly that anti-nucleic acid Abs equivalent to those found in SLE patients can be derived from cells of apparently normal individuals. As idiotypes are the serologic markers of immunoglobulin variable region genes, the existence of a common cross-reactive idiotype shared by both normal and SLE lymphocytes, implies that anti-nucleic acid Abs are encoded by common variable region genes present throughout the normal human populations

The effect of sex on immune responses to a homocitrullinated peptide in the DR4-transgenic mouse model of Rheumatoid Arthritis

© 2020 The Author(s) Rheumatoid Arthritis (RA) is more common and severe in women compared to men. Both women and men with RA express autoantibodies to post-translationally modified antigens, including citrullinated and homocitrullinated proteins or peptides. These autoantibodies are strongly linked with the HLA-DR4 gene. The objective of this study was to determine sex differences in immune responses to homocitrullinated antigens. We used a humanized animal model of RA, DR4-transgenic mice and immunized them with a homocitrullinated peptide called HomoCitJED. Immune responses in these mice were measured for splenocyte proliferation by tritiated thymidine incorporation, serum autoantibody production by ELISA and cytokine levels by multiplex. We found that T cell and antibody responses to homocitrullinated antigens were similar in male and female mice. However, we found sex differences in serum cytokine profiles with female mice having higher ratio of IL-1α to IL-5, suggesting imbalances in immune regulation. This is the first study to report that immune responses to homocitrullinated antigens can be differentiated by sex

The relationship between predicted peptide–MHC class II affinity and T-cell activation in a HLA-DRβ1*0401 transgenic mouse model

The HLA-DRB1*0401 MHC class II molecule (DR4) is genetically associated with rheumatoid arthritis. It has been proposed that this MHC class II molecule participates in disease pathogenesis by presenting arthritogenic endogenous or exogenous peptides to CD4(+) T cells, leading to their activation and resulting in an inflammatory response within the synovium. In order to better understand DR4 restricted T cell activation, we analyzed the candidate arthritogenic antigens type II collagen, human aggrecan, and the hepatitis B surface antigen for T-cell epitopes using a predictive model for determining peptide–DR4 affinity. We also applied this model to determine whether cross-reactive T-cell epitopes can be predicted based on known MHC–peptide–TCR interactions. Using the HLA-DR4-IE transgenic mouse, we showed that both T-cell proliferation and Th1 cytokine production (IFN-γ) correlate with the predicted affinity of a peptide for DR4. In addition, we provide evidence that TCR recognition of a peptide–DR4 complex is highly specific in that similar antigenic peptide sequences, containing identical amino acids at TCR contact positions, do not activate the same population of T cells

Arthritis induced by posttranslationally modified (citrullinated) fibrinogen in DR4-IE transgenic mice

Rheumatoid arthritis (RA) is a common autoimmune disease that afflicts the synovium of diarthrodial joints. The pathogenic mechanisms inciting this disease are not fully characterized, but may involve the loss of tolerance to posttranslationally modified (citrullinated) antigens. We have demonstrated that this modification leads to a selective increase in antigenic peptide affinity for major histocompatibility complex (MHC) class II molecules that carry the RA-associated shared epitope, such as HLA-DRB1*0401 (DR4). We describe the induction of arthritis in DR4-IE transgenic (tg) mice with citrullinated fibrinogen, a protein commonly found in inflamed synovial tissue and a frequent target of autoantibodies in RA patients. The disease induced in these mice was characterized by synovial hyperplasia followed by ankylosis, but lacked a conspicuous polymorphonuclear cell infiltrate. Immunological analysis of these mice through T cell epitope scanning and antibody microarray analysis identified a unique profile of citrulline-specific reactivity that was not found in DR4-IE tg mice immunized with unmodified fibrinogen or in wild-type C57BL/6 mice immunized with citrullinated fibrinogen, two conditions where arthritis was not observed. These observations directly implicate citrullinated fibrinogen as arthritogenic in the context of RA-associated MHC class II molecules

Mice with Mutation in Dynein Heavy Chain 1 Do Not Share the Same Tau Expression Pattern with Mice with SOD1-Related Motor Neuron Disease

Due to controversy about the involvement of Dync1h1 mutation in pathogenesis of motor neuron disease, we investigated expression of tau protein in transgenic hybrid mice with Dync1h1 (so-called Cra1/+), SOD1G93A (SOD1/+), double (Cra1/SOD1) mutations and wild-type controls. Total tau-mRNA and isoforms 0, 1 and 2 N expression was studied in frontal cortex, hippocampus, spinal cord and cerebellum of presymptomatic and symptomatic animals (age 70, 140 and 365 days). The most significant differences were found in brain cortex and cerebellum, but not in hippocampus and spinal cord. There were less changes in Cra1/SOD1 double heterozygotes compared to mice harboring single mutations. The differences in total tau expression and in profile of its isoforms between Cra1/+ and SOD1/+ transgenics indicate a distinct pathogenic entity of these two conditions

Representing Erasmus : approaches to Erasmus+ and consequences for researching the programme

This chapter looks at different methodological approaches to researching the Erasmus programme, specifically a macro-level analysis of trends in participation, micro-level studies of small groups of students and a meso-level exploration of the programme's institutional level. Taking each of these approaches in turn, we highlight the relative strengths and weaknesses of each position, the ways different audiences use different outputs and challenges for researchers in adopting and combining approaches. We also consider how research on Erasmus has adapted to change within the programme during the current Erasmus+ phase, including a heightened emphasis on non-student mobility

Peanut and horse radish peroxidase isoenzymes. Intraspecies and interspecies immunological relatedness

The presence of structural similarities in peroxidase isoenzymes was demonstrated by the technique of crossed immunoelec‐trophoresis. Isoenzymes found in the medium of peanut (Arachis hypogaea L.) cells grown in suspension culture were immuno‐precipitated in different arc systems according to the extent of relatedness of their antigenic determinants. Cross reactivity between isoenzymes in the medium was confirmed by demonstration that antibodies raised against only the glycoprotein fraction of the medium peroxidases would react also with the non‐glycosylated peroxidase isoenzymes that did not have affinity for Concanavalin A. Different peroxidase isoenzsmes from peanut leaves, peanut calli and peanut suspension cell medium share common antigenic determinants. Antibodies against peroxidase antigens from a different species, horse radish (Armoracia lapathifolia Gilib.), reacted with peroxidase antigens in the peanut cell medium. The results suggest a similarity of peanut peroxidases to horse radish peroxidase and. therefore, an evolutionary conservatism in peroxidase structure. The results also point to the potential utility of immunochemistry, including microcomplement fixation, to quantitate the structural similarities of peroxidase isoenzymes. Copyright © 1980, Wiley Blackwell. All rights reserve

O mobilności i migracjach młodych ludzi

The aim of this chapter is to introduce some of the conceptual tools researchers have developed to help explain young people’s spatial movement, especially in education, work and training contexts. This includes a reappraisal of the relationship between mobility and migration, seeing them as nested practices rather than distinct. The chapters also discuss how mobility is imaginatively integrated into life planning, with moving abroad while young potentially initiating a migration trajectory. This work is, we hope, an appropriate starting point for this book in establishing a starting point for mobility and arguing that what happens in the youth phase has lasting value.info:eu-repo/semantics/acceptedVersio