Non-conventional forms of HLA-B27 are expressed in spondyloarthritis joints and gut tissue

AbstractObjectivesHuman leukocyte antigen (HLA)-B27 (B27) is the strongest genetic factor associated with development of Ankylosing Spondylitis and other spondyloarthropathies (SpA), yet the role it plays in disease pathogenesis remains unclear. We investigated the expression of potentially pathogenic non-conventional heavy chain forms (NC) of B27 in synovial and intestinal tissues obtained from SpA patients. We also determined the presence of NC-B27 in joints, lymphoid and gastrointestinal tissue from B27 transgenic (TG1) rats with M.tuberculosis-induced SpA.MethodsExpression of NC-B27 in human SpA joints and gut and in (21-3 × 283-2)F1 HLA-B27/Huβ2m rat tissue was determined by immunohistochemistry, flow cytometry and confocal microscopy analysis using HC10 and HD6 antibodies.ResultsBoth HC10- and HD6-reactive HLA molecules were present in synovial tissue from SpA patients. Both NC-B27 and KIR3DL2, a ligand for NC-B27, were expressed in inflamed terminal ileal tissues in patients with early SpA. Infiltrating cells in inflamed joint tissues isolated from B27 TG1 rats expressed high levels of NC-B27. NC-B27 were also expressed in joint-resident cells from ankle and tail joints of B27 TG1 rats prior to clinical arthritis. The expression of NC-B27 on B27 TG1 rat CD11b/c+, CD8α+, cells from spleens and LNs increased with animal age and disease progression.ConclusionsNon-conventional HLA class 1 molecules are expressed on resident and infiltrating cells in both synovial and GI tissues in human SpA. NC-B27 expression in joints and lymphoid tissues from B27 TG1 rats prior to the onset of arthritis is consistent with the hypothesis that they play a pathogenic role in SpA

INTANGIBLE HERITAGE SIGNIFICANCE FOR NATIONAL IDENTITY

Culture? A commonplace — a term assimilated by every individual, yet understood by few. Tradition is a series of manifestations viewed from far, where they have not entered yet the shadow cone of forgetfulness, something that does not attract us anymore, a product of an antiquated society. We could affirm that what belongs to us is within our reach, and what belongs to somebody else is tempting… Harassed by the context of a modern society, we forget to look soberly at the origins that define each one of us and on whose basis we defined our civic, ethical, moral and professional personality

Application of a dried blood spot based proteomic and genetic assay for diagnosing hereditary angioedema

Abstract Background Hereditary angioedema (HAE) with C1‐inhibitor deficiency (C1‐INH‐HAE) is a rare disease caused by low level (type I) or dysfunction (type II) of the C1‐inhibitor protein with subsequent reduction of certain complement protein levels. Methods To develop and test the reliability of a two‐tier method based on C1‐INH and C4 quantitation followed by genetic analysis from dried blood spot (DBS) for establishing the diagnosis of C1‐INH‐HAE. C1‐INH and C4 proteins have been quantified in human plasma using a classical immuno‐assay and in DBS using a newly developed proteolytic liquid chromatography–mass spectrometry method. Genetic analysis was carried out as reported previously (PMID: 35386643) and by a targeted next‐generation sequencing panel, multiplex ligation‐dependent probe amplification and in some cases whole genome sequencing. Results DBS quantification of C1‐INH and C4 showed the same pattern as plasma, offering the possibility of screening patients with AE symptoms either locally or remotely. Genetic analysis from DBS verified each of the previously identified SERPING1 mutations of the tested C1‐INH‐HAE patients and revealed the presence of other rare variations in genes that may be involved in the pathogenesis of AE episodes. Conclusions C1‐INH/C4 quantification in DBS can be used for screening of hereditary AE and DNA extracted from dried blood spots is suitable for identifying various types of mutations of the SERPING1 gene

Molecular Composition of Sub-stoichiometrically Labeled alpha-Synuclein Oligomers Determined by Single-Molecule Photobleaching.

Item does not contain fulltextBleaching proteins: Single-molecule photobleaching approaches and sub-stoichiometric labeling with fluorophores give insight into the number of monomers that form a specific alpha-synuclein oligomer. The results show that this alpha-synuclein oligomer is present as a single, well-defined species consisting of 31 monomers

A general approach for geometric error modeling of lower mobility parallel manipulators

This paper presents a general and systematic approach for geometric error modeling of lower mobility manipulators. The approach can be implemented in three steps: (1) development of a linear map between the pose error twist and source errors within an individual limb using the homogeneous transformation matrix method; (2) formulation of a linear map between the pose error twist and the joint error intensities of a lower mobility parallel manipulator; and (3) combination of these two models. The merit of this approach lies in that it enables the source errors affecting the compensatable and uncompensatable pose accuracy of the platform to be explicitly separated, thereby providing designers and/or field engineers with an informative guideline for the accuracy improvement achievable by suitable measures, i.e., component tolerancing in design, manufacturing and assembly processes, and kinematic calibration. Three typical and well-known parallel manipulators are taken as examples to illustrate the generality and effectiveness of this approach. [DOI: 10.1115/1.4003845