Search results for "HLA"

Kosket kylän keskellä : tutkimus muistamisesta, kyläyhteisöstä ja vesivoimasta Kuhmoisten Pihlajakoskella

2010

Role of Human Leukocyte Antigens (HLA) in Autoimmune Diseases

2018

Since the discovery of HLA 60 years ago, it has contributed to the understanding of the immune system as well as of the pathogenesis of several diseases. Aside from its essential role in determining donor-recipient immune compatibility in organ transplantation, HLA genotyping is meanwhile performed routinely as part of the diagnostic work-up of certain autoimmune diseases. Considering the ability of HLA to influence thymic selection as well as peripheral anergy of T cells, its role in the pathogenesis of autoimmunity is understandable. The aim of this paper is to provide a brief overview of the role and current clinical relevance of HLA-B27 in spondyloarthritis and HLA-B51 in Behçet's disea…

2016

Objectives Human 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.

FRI0150 Mtor blockade by rapamycin decreases arthritis and spondylitis development and severity in hla-b27 transgenic rats

2018

Career situation of first and presenting author Student for a master or a PhD. Introduction TNF and IL-17A have been demonstrated as key inflammatory cytokines in Spondyloarthritis (SpA), whereas targeting bone remodeling remains an unmet clinical need in SpA. The mammalian target of rapamycin (mTOR) regulates IL-17 expression and osteogenesis and could therefore be a promising therapeutic target in SpA. Objectives To investigate if blockade of mTOR with rapamycin inhibits the pathological processes in inflammation and bone in SpA. Methods Cytokines were measured by ELISA in the supernatant from SpA patient PBMCs stimulated with anti-CD3/CD28, with various concentrations of rapamycin. SpA F…

HLA-B27-restricted T cells from patients with ankylosing spondylitis recognize peptides from B*2705 that are similar to bacteria-derived peptides

2003

SUMMARY Ankylosing spondylitis (AS) is an inflammatory systemic disease affecting the spine, sacroiliacal and peripheral joints. Although the aetiology of AS remains unknown, the strong association with the HLA-B27 allele might reflect directly a detrimental effect of the HLA-B27 molecule itself, resulting from its potential capability to present ‘arthritogenic’ peptides to CD8+ T cells. Because some forms of SpA are triggered by enterobacterial infection, such arthritogenic peptides might originate from autologous and/or bacterial proteins triggering cross-reactive CD8+ T cell clones. Intriguingly, two peptides from the second extracellular domain of HLA-B*2705 share sequence homologies wi…

HLA-B27-restricted CD8 T cells derived from synovial fluids of patients with reactive arthritis and ankylosing spondylitis.

1993

Ankylosing spondylitis and seronegative spondylarthropathies such as Reiter's syndrome and reactive arthritis are strongly associated with HLA-B27. However, the mechanisms by which HLA-B27 is involved in disease susceptibility and pathogenesis are unknown. If the disease association is a consequence of HLA-B27's physiological function in antigen presentation, the disease should be mediated by cytotoxic T lymphocytes (CTLs) that recognise bacterial or self peptides presented by HLA-B27. Proof of this arthritogenic peptide model requires isolation of B27-restricted CD8 T cells from arthritic joints of patients with spondylarthropathies. An important question is whether "arthritogenic" bacteri…

HLA-B27-restricted cytotoxic T lymphocyte responses to arthritogenic enterobacteria or self-antigens are dominated by closely related TCRBV gene segm…

1996

Identification of the T-cell receptors (TCR) used by synovial cytotoxic T lymphocytes (CTL) of patients with reactive arthritis (ReA) may be crucial to better understanding the pathogenetic mechanism underlying the HLA-B27 association of spondylarthropathies. The authors, therefore, sequenced 25 TCRB chains from HLA-B27-restricted CD8+ CTL clones and two clonal lines specific for self- or Yersinia enterocolitica antigen isolated from synovial fluids of 3 HLA-B27+ patients with ReA and PBL of one healthy HLA-B27+ individual. Fourteen non-HLA-B27-restricted CTL served as controls. Both autoreactive and Y. enterocolitica specific HLA-B27-restricted CTL used a highly limited set of VB genes wit…

Analysis of HLA-DRB1,DQA1,DQB1 haplotypes in Sardinian centenarians

2008

Some genetic determinants of longevity might reside in those polymorphisms for the immune system genes that regulate immune responses. Many longevity association studies focused their attention on HLA (the human MHC) polymorphisms, but discordant results have been obtained. Sardinians are a relatively isolate population and represent a suitable population for association studies. Some HLA-DR and DQ alleles form very stable haplotypes with a strong linkage disequilibrium. In a previous study on Sardinian centenarians we have suggested that HLA-DRB1 *15 allele might be marginally associated to longevity. HLA-DR,DQ haplotypes are in strong linkage disequilibrium and well conserved playing a ro…

FRI0194 Is There an Association Between Spondyloarthritis and Antibodies Towards Borrelia, Ehrlichia and Chlamydia Species?

2015

Background Several studies suggested that certain microorganisms might contribute to initiation and perpetuation of spondyloarthritis (SpA). Objectives To investigate IgG and IgM antibodies towards Borrelia burgdorferi (Bb), Borrelia garinii (Bg), Borrelia afzelii (Ba), Ehrlichia spp. (Ehr), Chlamydia trachomatis (Ct), and Chlamydia pneumoniae (Cp) in SpA patients, low back pain patients, and healthy subjects and to elucidate whether previous infections could play a role in the onset of SpA. Methods Data collection was based on persons aged 18-40 years referred with low back pain for ≥3 months. They were examined with MRI of the spine and sacroiliac joints, CRP, HLA-B27, and clinical SpA fe…

Bacteria-specific cytotoxic CD8+ T cells: a missing link in the pathogenesis of the HLA-B27-associated spondylarthropathies.

1994

The term seronegative spondylarthropathies is used for an entity of rheumatic syndromes of peripheral joints and the spine (ankylosing spondylitis, reactive arthritis, Reiter's syndrome, arthritis in psoriasis and in inflammatory bowel disease) which are strongly associated with the MHC class I molecule HLA-B27. However, the mechanisms whereby HLA-B27 confers disease susceptibility have so far remained unknown. There is strong evidence that gut inflammation and infection with gram-negative bacteria play a role in the induction of B27-associated disease. HLA-B27, like other MHC class I molecules, physiologically binds antigenic peptides in its binding groove and presents them to CD8+ T lymph…