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

The Lancet ◽  
1993 ◽  
Vol 342 (8872) ◽  
pp. 646-650 ◽  
Author(s):  
E. Hermann ◽  
K-H. Meyer zum Büschenfelde ◽  
B. Fleischer ◽  
D.T.Y. Yu
Keyword(s):  
T Cells ◽  
Ankylosing Spondylitis ◽  
Cd8 T Cells ◽  
Reactive Arthritis ◽  
Hla B27 ◽  
Synovial Fluids

Arthritis and Foodborne Bacteria

1994 ◽  
Vol 57 (10) ◽  
pp. 935-941 ◽  
Author(s):  
JAMES L. SMITH
Keyword(s):  
T Cells ◽  
Ankylosing Spondylitis ◽  
Reactive Arthritis ◽  
Molecular Mimicry ◽  
Food Poisoning ◽  
Cell Subset ◽  
Bacterial Cells ◽  
Hla B27 ◽  
Reiter's Syndrome ◽  
Reiter’S Syndrome

Diarrheic episodes caused by the foodborne pathogens Campylobacter, Salmonella, Shigella or Yersinia may lead to a sterile arthritis such as reactive arthritis, Reiter's syndrome or ankylosing spondylitis. Reiter's syndrome and reactive arthritis have been shown to be sequelae in a few well-studied bacterial food poisoning outbreaks. Reactive arthritis, Reiter's syndrome and ankylosing spondylitis show strong familial association related to the gene for HLA-B27 (HLA = human leucocyte antigen) antigen. Why HLA-B27-positive individuals are more susceptible to arthritis is not known, but molecular mimicry between the HLA-B27 antigen and antigens of triggering bacteria has been demonstrated and this mimicry has been proposed as a mechanism involved in etiology of the arthritides. Antigens from bacteria that triggered the arthritis are present in arthritic joints but bacterial cells are not found. Antibodies and T-cells specific for the triggering bacteria have been demonstrated in arthritic patients. T-cells present in synovial joints respond specifically to the particular arthritic triggering pathogen. The cells that respond to bacterial antigens belong to the T-cell subset TH1 that secrete a limited number of cytokines but it is not known if cytokines are involved in arthritis. A few studies have demonstrated that T-cells from the joints of arthritic patients respond to both bacterial and human heat shock proteins indicating that autoimmunity may be involved in causation of arthritis. While only about 2% of a population exposed to a triggering infection will acquire arthritis, these individuals undergo pain and suffering as well as economic hardships as a result of their disease.

scholarly journals HLA-B27-restricted antigen presentation by human chondrocytes to CD8+ T cells: Potential contribution to local immunopathologic processes in ankylosing spondylitis

2009 ◽  
Vol 60 (6) ◽  
pp. 1635-1646 ◽  
Author(s):  
Maren Kuhne ◽  
Ulrike Erben ◽  
Gundula Schulze-Tanzil ◽  
Dorothee Köhler ◽  
Peihua Wu ◽  
...  
Keyword(s):  
T Cells ◽  
Ankylosing Spondylitis ◽  
Antigen Presentation ◽  
Cd8 T Cells ◽  
Human Chondrocytes ◽  
Potential Contribution ◽  
Hla B27

scholarly journals Unusual Placement of an EBV Epitope into the Groove of the Ankylosing Spondylitis-Associated HLA-B27 Allele Allows CD8+ T Cell Activation

Cells ◽  
2019 ◽  
Vol 8 (6) ◽  
pp. 572 ◽  
Author(s):  
Valentina Tedeschi ◽  
Josephine Alba ◽  
Fabiana Paladini ◽  
Marino Paroli ◽  
Alberto Cauli ◽  
...  
Keyword(s):  
T Cells ◽  
Ankylosing Spondylitis ◽  
T Cell ◽  
T Cell Activation ◽  
Cd8 T Cells ◽  
Cell Activation ◽  
Molecular Mechanisms ◽  
Axial Skeleton ◽  
Binding Motif ◽  
Hla B27

The human leukocyte antigen HLA-B27 is a strong risk factor for Ankylosing Spondylitis (AS), an immune-mediated disorder affecting axial skeleton and sacroiliac joints. Additionally, evidence exists sustaining a strong protective role for HLA-B27 in viral infections. These two aspects could stem from common molecular mechanisms. Recently, we have found that the HLA-B*2705 presents an EBV epitope (pEBNA3A-RPPIFIRRL), lacking the canonical B27 binding motif but known as immunodominant in the HLA-B7 context of presentation. Notably, 69% of B*2705 carriers, mostly patients with AS, possess B*2705-restricted, pEBNA3A-specific CD8+ T cells. Contrarily, the non-AS-associated B*2709 allele, distinguished from the B*2705 by the single His116Asp polymorphism, is unable to display this peptide and, accordingly, B*2709 healthy subjects do not unleash specific T cell responses. Herein, we investigated whether the reactivity towards pEBNA3A could be a side effect of the recognition of the natural longer peptide (pKEBNA3A) having the classical B27 consensus (KRPPIFIRRL). The stimulation of PBMC from B*2705 positive patients with AS in parallel with both pEBNA3A and pKEBNA3A did not allow to reach an unambiguous conclusion since the differences in the magnitude of the response measured as percentage of IFNγ-producing CD8+ T cells were not statistically significant. Interestingly, computational analysis suggested a structural shift of pEBNA3A as well as of pKEBNA3A into the B27 grooves, leaving the A pocket partially unfilled. To our knowledge this is the first report of a viral peptide: HLA-B27 complex recognized by TCRs in spite of a partially empty groove. This implies a rethinking of the actual B27 immunopeptidome crucial for viral immune-surveillance and autoimmunity.

Absence of cross-reaction between HLA B27 and yersinia enterocolitica or chlamydia trachomatis in reactive arthritis and ankylosing spondylitis

1985 ◽  
Vol 4 (4) ◽  
pp. 487-487 ◽  
Author(s):  
J. Roudier ◽  
H. De Montclos ◽  
D. Thouvenot ◽  
J. J. Chomel ◽  
F. N. Guillermet ◽  
...  
Keyword(s):  
Ankylosing Spondylitis ◽  
Chlamydia Trachomatis ◽  
Yersinia Enterocolitica ◽  
Reactive Arthritis ◽  
Cross Reaction ◽  
Hla B27

scholarly journals A comparative study of HLA genes in HLA–B27 positive ankylosing spondylitis and HLA–B27 positive peripheral reactive arthritis

1996 ◽  
Vol 39 (6) ◽  
pp. 943-949 ◽  
Author(s):  
Pia Westman ◽  
Marjatta Leirisalo-Repo ◽  
Jukka Partanen ◽  
Saija Koskimies
Keyword(s):  
Ankylosing Spondylitis ◽  
Comparative Study ◽  
Reactive Arthritis ◽  
Hla B27 ◽  
Hla Genes

scholarly journals A RUNX3 enhancer polymorphism associated with ankylosing spondylitis influences recruitment of Interferon Regulatory Factor 5 and factors of the Nucleosome Remodelling Deacetylase Complex in CD8+ T-cells

2019 ◽  
Author(s):  
Matteo Vecellio ◽  
Adrian Cortes ◽  
Sarah Bonham ◽  
Carlo Selmi ◽  
Julian C Knight ◽  
...  
Keyword(s):  
T Cells ◽  
Ankylosing Spondylitis ◽  
Cd8 T Cells ◽  
Binding Protein ◽  
Interferon Regulatory Factor ◽  
Regulatory Factor ◽  
Nurd Complex ◽  
Nucleosome Remodeling ◽  
Nuclear Extracts ◽  
Functional Consequences

ABSTRACTObjectivesTo investigate the functional consequences of the single nucleotide polymorphism rs4648889 in a putative enhancer upstream of the RUNX3 promoter strongly associated with ankylosing spondylitis (AS).MethodsThe effects of rs4648889 on transcription factor (TF) binding were tested by DNA pull-down and quantitative mass spectrometry. The results were validated by electrophoretic mobility gel shift assays (EMSA), Western blot (WB) analysis of the pulled-down eluates, and chromatin immuno-precipitation (ChIP)-qPCR.ResultsSeveral TFs showed differential allelic binding to a 50bp DNA probe spanning rs4648889. Binding was increased to the AS-risk A allele for IKZF3 (aiolos) in nuclear extracts from CD8+ T-cells (3.7-fold, p<0.03) and several components of the NUcleosome Remodeling Deacetylase (NuRD) complex, including Chromodomain-Helicase-DNA-binding protein 4 (3.6-fold, p<0.05) and Retinoblastoma-Binding Protein 4 (4.1-fold, p<0.02). In contrast, binding of interferon regulatory factor (IRF) 5 was increased to the AS-protective G allele. These results were confirmed by EMSA, WB and ChIP-qPCR.ConclusionsThe association of AS with rs4648889 most likely results from its influence on the binding of this enhancer-like region to TFs, including IRF5, IKZF3 and members of the NuRD complex. Further investigation of these factors and RUNX3-related pathways may reveal important new therapeutic possibilities in AS.

Influence of HLA-B*5703 and HLA-B*1403 on Susceptibility to Spondyloarthropathies in the Zambian Population

2008 ◽  
Vol 35 (11) ◽  
pp. 2236-2240 ◽  
Author(s):  
ROBERTO DÍAZ-PEÑA ◽  
MIGUEL ANGEL BLANCO-GELAZ ◽  
PANGANANI NJOBVU ◽  
ANTONIO LÓPEZ-VAZQUEZ ◽  
BEATRIZ SUÁREZ-ÁLVAREZ ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Ankylosing Spondylitis ◽  
Reactive Arthritis ◽  
Hiv Positive ◽  
Sample Population ◽  
Type I ◽  
Hla B27 ◽  
New Findings ◽  
Immunodeficiency Virus ◽  
Sub Saharan

ObjectiveTo analyze the distribution of HLA-B alleles and to investigate their contribution in the susceptibility to spondyloarthropathies (SpA) in a sample population from Zambia, in order to determine a relationship between some HLA-B alleles and development of ankylosing spondylitis (AS), reactive arthritis (ReA), or undifferentiated SpA (uSpA).MethodsWe selected 72 patients with SpA and found that 46 had uSpA, 23 ReA, and 3AS.We also selected 92 matched controls; 55 of these had human immunodeficiency virus type I (HIV-I) infection.ResultsWe found a significant increase in the rate of uSpA and ReA with features of Reiter’s syndrome (RS) in HIV-positive individuals who carried the HLA-B*5703 allele (pc < 0.0001 and pc < 0.001, respectively). Among the significant new findings identified were the presence of B*1403 in 2 of the 3 AS patients (pc < 0.05, OR 47), confirming previous data in the Togolese population.ConclusionThe presence of B*5703 and HIV infection may not affect susceptibility to AS and ReA, but they do show an important influence in uSpA and RS. Our findings confirm that HLA-B* 1403 is the only factor to increase the risk of AS in a sub-Saharan African population, whereas HLA-B27 was virtually absent in patients with AS.

scholarly journals Enterobacteria‐Infected T Cells as Antigen‐Presenting Cells for Cytotoxic CD8 T Cells: A Contribution to the Self‐Limitation of Cellular Immune Reactions in Reactive Arthritis?

1997 ◽  
Vol 175 (5) ◽  
pp. 1121-1127 ◽  
Author(s):  
Birgit Ackermann ◽  
Martin S. Staege ◽  
Angelika B. Reske‐Kunz ◽  
Hans‐Peter Dienes ◽  
Karl‐Hermann Meyer zum Büschenfelde ◽  
...  
Keyword(s):  
T Cells ◽  
Cd8 T Cells ◽  
Reactive Arthritis ◽  
Antigen Presenting Cells ◽  
The Self ◽  
Immune Reactions ◽  
Cellular Immune ◽  
Antigen Presenting
Sign in / Sign up

Export Citation Format

Share Document