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Ectopic expression of CXCL13, BAFF, APRIL and LT-ß is associated with artery tertiary lymphoid organs in giant cell arteritis

2016

ObjectivesTo investigate whether artery tertiary lymphoid organs (ATLOs) are present in giant cell arteritis (GCA) and that their formation is associated with the ectopic expression of constitutive lymphoid tissue-homing chemokines.MethodsReverse transcriptase PCR, immunohistochemical and immunofluorescence analysis were used to determine the presence of ectopic ATLOs in GCA and the expression of chemokines/chemokine receptors and cytokines involved in lymphoneogenesis in the temporal artery samples obtained from 50 patients with GCA and 30 controls. The presence of lymphatic conduits, of follicular dendritic cells (FDCs) precursors and lymphoid tissue inducer cells was also investigated. F…

Clinical efficacy of α4 integrin block with natalizumab in ankylosing spondylitis

2016

We describe the impact of α4-β1/7 blockade with natalizumab, a recombinant humanised immunoglobulin (Ig) G4κ monoclonal antibody (mAb) targeted to the α4 subunit of the α4β1 and α4β7 integrins, on the gut and spine inflammation in a patient with ankylosing spondylitis (AS) who developed multiple sclerosis after treatment with tumour necrosis factor (TNF)-blocking agents. A 45-year-old man with human leucocyte antigen (HLA)-B27-positive AS was admitted in January 2007. He had been diagnosed with AS 4 years earlier based on the presence of inflammatory back pain, peripheral arthritis, radiographic bilateral grade 2 sacroiliitis, HLA-B27 positivity. At that time, he had evidence of chronic int…

Response to: 'Artery tertiary lymphoid organs in giant cell arteritis are not exclusively located in the media of temporal arteries' by Graver et al

2017

We thank Graver  et al 1 for their interest in our recently published article on artery tertiary lymphoid organs (ATLOs) in giant cell arteritis (GCA).2 The authors stained temporal artery biopsies of 21 biopsy-proven GCA patients (71% female, mean duration of disease of 2.3±0.9 months) that fulfilled the 1990 American College of Rheumatology classification criteria with anti-CD20 and anti-CD3 antibodies. On the basis of this experimental approach, they confirmed the presence of ATLOs only in the adventitia of inflamed arteries of GCA patients and not in the media as demonstrated in our study. This statement, however, is not supported in our opinion by the experimental approach chosen …

On the pathogenicity of the plasminogen K330E mutation for hereditary angioedema

2018

2020

Lipoprotein(a) [Lp(a)] is a major cardiovascular risk factor, which is largely genetically determined by one major gene locus, the LPA gene. Many aspects of the transcriptional regulation of LPA are poorly understood and the role of epigenetics has not been addressed yet. Therefore, we conducted an epigenome-wide analysis of DNA methylation on Lp(a) levels in two population-based studies (total n = 2208). We identified a CpG site in the LPA promoter which was significantly associated with Lp(a) concentrations. Surprisingly, the identified CpG site was found to overlap the SNP rs76735376. We genotyped this SNP de-novo in three studies (total n = 7512). The minor allele of rs76735376 (1.1% mi…

Risk of Classic Kaposi Sarcoma With Combinations of Killer Immunoglobulin-Like Receptor and Human Leukocyte Antigen Loci: A Population-Based Case-con…

2015

BACKGROUND Kaposi sarcoma (KS) is a complication of KS-associated herpesvirus (KSHV) infection. Other oncogenic viral infections and malignancies are associated with certain HLA alleles and their natural killer (NK) cell immunoglobulin-like receptor (KIR) ligands. We tested whether HLA-KIR influences the risk of KSHV infection or KS. METHODS In population-based case-control studies, we compared HLA class I and KIR gene frequencies in 250 classic (non-AIDS) KS cases, 280 KSHV-seropositive controls, and 576 KSHV-seronegative controls composing discovery and validation cohorts. Logistic regression was used to calculate sex- and age-adjusted odds ratios (ORs) and 95% confidence intervals. RESUL…

BDE-47 exposure modulates cellular responses, oxidative stress and biotransformation related-genes in Mytilus galloprovincialis.

2020

Abstract Polybrominated diphenyl ethers (PBDEs) are flame retardants, characterized by elevated stability in the marine environment, where are accumulated by organisms, inducing a wide panel of negative effects. In this study, some biochemical patterns related to toxicity, biotransformation and oxidative stress, were studied in the marine model system, Mytilus galloprovincialis, exposed to BDE-47. Mussels were fed with microalgae, previously treated with increasing concentrations of PBDEs (maximum dose 100 ng L-1 of BDE-47 per day). After 15 days of treatment, mussels were fed with the same diet without BDE-47, for additional 15 days. Gills and digestive glands were analyzed at T 0, at 15 a…

Binding and neurotoxicity mitigation of toxic tau oligomers by synthetic heparin like oligosaccharides.

2018

Well-defined heparin like oligosaccharides up to decasaccharides were synthesized. It was discovered for the first time that heparin oligosaccharides, as short as tetrasaccharides, can bind with the most toxic tau species, i.e., tau oligomers with nM KD. The binding significantly reduced the cellular uptake of toxic tau oligomers and protected the cells from tau oligomer induced cytotoxicity.

The immunoglobulin γ marker 17 allotype and KIR/HLA genes prevent the development of chronic hepatitis B in humans

2020

Hepatitis B virus (HBV) infection causes a self-limiting disease in most individuals. However, < 10% of infected subjects develop a chronic disease. Genetic host variability of polymorphic genes at the interface of innate and acquired immunity, such as killer immunoglobulin-like receptors (KIR), their human leucocyte antigen (HLA) and IgG allotypes (GM), could explain this different clinical picture. We previously showed a protective role of the KIR2DL3 gene for the development of chronic hepatitis B (CHB), and a detrimental role of the KIR ligand groups, HLA-A-Bw4 and HLA-C2. We have expanded the previous analysis genotyping patients for GM23 and GM3/17 allotypes. The comparison of the …

Association between γ marker, human leucocyte antigens and killer immunoglobulin‐like receptors and the natural course of human cytomegalovirus infec…

2017

Natural killer (NK) cells provide a major defence against cytomegalovirus (HCMV) infection through the interaction of their surface receptors, including the activating and inhibitory killer immunoglobulin-like receptors (KIRs), and human leukocyte antigens (HLA) class I molecules. Also GM allotypes, able to influence the NK antibody-dependent cell-mediated cytotoxicity (ADCC), appear to be involved in the immunological control of virus infections, including HCMV. In some cases, their contribution requires epistatic interaction with other genes of the immune system, such as HLA. In the present report, with the aim to gain insight into the immune mechanisms controlling HCMV, we have studied t…