scholarly journals Antibody activity in ankylosing spondylitis sera to two sites on HLA B27.1 at the MHC groove region (within sequence 65-85), and to a Klebsiella pneumoniae nitrogenase reductase peptide (within sequence 181-199).

1990 ◽  
Vol 171 (5) ◽  
pp. 1635-1647 ◽  
Author(s):  
C Ewing ◽  
R Ebringer ◽  
G Tribbick ◽  
H M Geysen
Keyword(s):  
Amino Acids ◽  
Ankylosing Spondylitis ◽  
Klebsiella Pneumoniae ◽  
Homologous Sequence ◽  
Antibody Activity ◽  
Healthy Controls ◽  
Hla B27 ◽  
Reactive Site ◽  
A Site ◽  
Groove Region

74 overlapping peptides of varying lengths from Klebsiella pneumoniae nitrogenase reductase (residues 181-199) and from the HLA B27.1 molecule (residues 65-85) were synthesized and tested by ELISA against sera from HLA B27+ ankylosing spondylitis (AS) patients, and sera from HLA B27+ and HLA B27- healthy first-degree relatives. Antibody activity in AS sera to Klebsiella peptides of four to eight amino acids was maximal with the peptide NSRQTDR. Activity to HLA B27 peptides was maximal with the peptide KAKAQTDR (named epitope I). These peptides overlap with, but are proximal to the NH2 terminus from QTDRED, which is homologous in HLA B27.1 and K. pneumoniae nitrogenase reductase. A second weaker reactive site was noted in the HLA B27.1 peptides, proximal to the COOH terminus from the homologous sequence, namely peptide REDLRTLL (named epitope II). Little activity was seen against peptides that included the entire homologous sequence. Sera from 50 AS patients showed higher total Ig activity against peptides KAKAQTDR (p less than 0.001) and NSRQTDR (p less than 0.02) than did sera from 22 B27+ and 22 B27- healthy controls. These data indicate that AS patient sera contain antibodies that bind to K. pneumoniae nitrogenase peptides and HLA B27.1 peptides, and that there are at least two epitopes on HLA B27.1 in the alpha 1 domain, at the MHC groove region, that are autoantigenic in AS patients. Epitope I may be a site for crossreactivity between HLA B27 and Klebsiella.

scholarly journals The Link between Ankylosing Spondylitis, Crohn’s Disease,Klebsiella, and Starch Consumption

2013 ◽  
Vol 2013 ◽  
pp. 1-9 ◽  
Author(s):  
Taha Rashid ◽  
Clyde Wilson ◽  
Alan Ebringer
Keyword(s):  
Crohn’S Disease ◽  
Ankylosing Spondylitis ◽  
Crohn's Disease ◽  
Klebsiella Pneumoniae ◽  
Dietary Intake ◽  
Therapeutic Effect ◽  
Hla B27 ◽  
Daily Dietary Intake ◽  
Pathological Lesions ◽  
Triggering Factor

Both ankylosing spondylitis (AS) and Crohn’s disease (CD) are chronic and potentially disabling interrelated conditions, which have been included under the group of spondyloarthropathies. The results of a large number of studies support the idea that an enteropathic pathogen,Klebsiella pneumoniae, is the most likely triggering factor involved in the initiation and development of these diseases. Increased starch consumptions by genetically susceptible individuals such as those possessing HLA-B27 allelotypes could trigger the disease in both AS and CD by enhancing the growth and perpetuation of theKlebsiellamicrobes in the bowel. Exposure to increased levels of these microbes will lead to the production of elevated levels of anti-Klebsiellaantibodies as well as autoantibodies against cross-reactive self-antigens with resultant pathological lesions in the bowel and joints. Hence, a decrease of starch-containing products in the daily dietary intake could have a beneficial therapeutic effect on the disease especially when used in conjunction with the currently available medical therapies in the treatment of patients with AS and CD.

HLA-B27 subtypes in Turkish patients with ankylosing spondylitis and healthy controls

2011 ◽  
Vol 32 (10) ◽  
pp. 3103-3105 ◽  
Author(s):  
Muradiye Acar ◽  
Tulin Cora ◽  
Recep Tunc ◽  
Hasan Acar
Keyword(s):  
Ankylosing Spondylitis ◽  
Healthy Controls ◽  
Hla B27 ◽  
Turkish Patients

scholarly journals Autoantibodies to HLA B27 in the sera of HLA B27 patients with ankylosing spondylitis and Reiter's syndrome. Molecular mimicry with Klebsiella pneumoniae as potential mechanism of autoimmune disease.

1987 ◽  
Vol 166 (1) ◽  
pp. 173-181 ◽  
Author(s):  
P L Schwimmbeck ◽  
D T Yu ◽  
M B Oldstone
Keyword(s):  
Ankylosing Spondylitis ◽  
Klebsiella Pneumoniae ◽  
Biological Significance ◽  
Amino Acid Sequences ◽  
Peptide Sequence ◽  
Autoimmune Response ◽  
Computer Search ◽  
Hla B27 ◽  
Reiter's Syndrome ◽  
Reiter’S Syndrome

Ankylosing spondylitis (AS) and Reiter's syndrome (RS) both show a strong correlation with the HLA B27 haplotype. We studied whether sharing of homologous amino acid sequences in the HLA B27 antigen with an invading microbe might occur, and if so, what is the biological significance of such homology. In a computer search of the Dayhoff data bank, we found a homology of six consecutive amino acids between HLA B27.1 antigen residues 72-77 and Klebsiella pneumoniae nitrogenase residues 188-193. These shared sequences are hydrophilic, suggesting locations on molecules exposed to the cell surface. Immunochemical analysis showed that 18 of 34 sera from patients with RS (53%) and 7 of 24 sera from patients with AS (29%) contained antibodies that bound to a synthesized peptide sequence representing residues 69-84 of HLA B27.1. In contrast, only 1 of 22 sera from healthy, B27+ controls (5%) contained antibodies to this peptide (p less than 0.01). Sera from three HLA B27- patients with RS did not possess antibodies to the HLA B27 peptide. Additionally, greater than 40% of HLA B27 patients with AS or RS had antibodies to Klebsiella residues 184-193, while none of the normal nonarthritic HLA B27 haplotype subjects did. Our results suggest that an autoimmune response(s) directed against HLA B27.1 may be a pathogenic mechanism in a subset of patients with AS and RS. Further, this response may initially be induced against Klebsiella pneumoniae, a microorganism that shares sequence homology with HLA B27.

A high density SNP genotyping approach within the 19q13 chromosome region identifies an association of a CNOT3 polymorphism with ankylosing spondylitis

2012 ◽  
Vol 71 (5) ◽  
pp. 714-717 ◽  
Author(s):  
Roberto Díaz-Peña ◽  
Ana M Aransay ◽  
Beatriz Suárez-Álvarez ◽  
Jacome Bruges-Armas ◽  
Naiara Rodríguez-Ezpeleta ◽  
...  
Keyword(s):  
Ankylosing Spondylitis ◽  
High Throughput ◽  
Human Leucocyte Antigen ◽  
Chromosome Region ◽  
Healthy Controls ◽  
Nucleotide Polymorphisms ◽  
Hla B27 ◽  
Single Nucleotide ◽  
Sliding Windows ◽  
Genomic Variants

ObjectiveTo identify genomic variants in the 19q13 chromosome region associated with ankylosing spondylitis (AS) in human leucocyte antigen (HLA)-B27-positive populations.MethodsHigh-throughput genotyping of 1536 haplotype-tag single nucleotide polymorphisms (SNPs) was performed in 249 patients with AS and 302 healthy controls. Some of the identified associations were validated by genotyping four SNPs in two additional cohorts consisting of 412 cases/301 controls and 144 cases/203 controls. All individuals selected (both cases and controls) were HLA-B27-positive.ResultsTwo markers in two different genes (CNOT3 and LAIR2) showed significant association (p<10−3) with AS. In addition, sliding windows analysis showed association of groups of adjacent SNPs in regions located around CNOT3 (Chr19: 59347459-59356564, p=2.43×10−4 to 6.54×10−4). The associations were validated by genotyping four SNPs from regions located near LAIR2 and CNOT3 genes (rs1055234, rs8111398, rs2287828 and rs4591276) in two additional cohorts. The CNOT3 polymorphism (rs1055234) remained associated with AS (combined p=9.73×10−6). One SNP, located downstream of KIR3DL1, was detected which, tested in combination with HLA-Bw4I80, was associated with AS.ConclusionA novel significant association was detected between SNP rs1055234 and AS susceptibility.

The association of HLA-B27 and Klebsiella pneumoniae in ankylosing spondylitis: A systematic review

2018 ◽  
Vol 117 ◽  
pp. 49-54 ◽  
Author(s):  
Li Zhang ◽  
Yan-Jie Zhang ◽  
Jin Chen ◽  
Xiao-Lei Huang ◽  
Gong-Si Fang ◽  
...  
Keyword(s):  
Systematic Review ◽  
Ankylosing Spondylitis ◽  
Klebsiella Pneumoniae ◽  
Hla B27
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