Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P01889 (ankylosing spondylitis)
 5,717 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The aim of this study was to search infections that trigger reactive arthritis. Eighty-six patients with seronegative arthritis (SNA) were studied; 32 had reactive arthritis, 21 ankylosing spondylitis, 7 psoriatic arthritis and 26 undifferentiated seronegative oligoarthritis. As controls, 70 patients with connective tissue diseases (CTD) and 55 healthy volunteers (HV) were studied. Serological evidence for infection with Chlamydia trachomatis was studied with micro immunofluorescence, looking for L2 and BED serotypes and serological evidence for Yersinia infection, using a commercial kit. Stool cultures were done in seven patients with recent diarrhea, and endourethral or endocervical cultures in 35 individuals. Serotypes L2 or BED were positive in 23 of 83 patients with SNA, 3 of 39 patients with CTD and 4 of 55 HV (p < 0.03). IgG class antibodies against L2 were detected in 17% of SNA patients, 2.6% of CTD patients and 5.4% of HV (p < 0.05). IgM class antibodies were detected in 6 SNA patients, 0 CTD patients and 2 HV (NS). Twelve of 35 cultures were positive for Chlamydia. As a whole 30% of SNA patients has serological or bacteriological evidence for Chlamydia infection. Serology for Yersinia was positive in 39 of 81 SNA patients, 1 of 54 CTD patients and 3 of 51 HV (p < 0.01). Rates of infections were similar among male, female, HLA B27 positive and HLA negative subjects. It is concluded that SNA patients have a high prevalence of infections by Chlamydia trachomatis or Yersinia enterocolitica.
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PMID:[Infection and reactive arthritis: clinico-bacteriological correlation in seronegative arthropathies]. 873 12

Acute anterior uveitis (AAU) and ankylosing spondylitis (AS) are, like reactive arthritis (ReA), strongly associated with HLA-B27. Mucosal infections play a role in the pathogenesis of ReA. To investigate whether these microorganisms are also involved in the pathogenesis of AAU and AS, we examined blood samples from patients with AAU, AS or both, and healthy controls for presence of antibodies against Klebsiella pneumoniae (K 30), Salmonella enteritidis and S. typhimurium, Chlamydia trachomatis, Proteus mirabilis and Borrelia burgdorferi. The IgA, IgG and IgM classes of these antibodies were measured using an enzyme-linked immunosorbent assay. No significant differences were found in the frequency in which these antibodies occurred in HLA-B27 positive patients with AAU or AS and healthy controls. However, IgA antibodies against K. pneumoniae (p < 0.01) and IgA and IgG antibodies against P. mirabilis (p < 0.01 and p < 0.05) were detected more frequently in HLA-B27 negative patients with AAU than in healthy controls. The results of this study are in contrast with various earlier reports in which antibodies against Klebsiella strains were more frequently found in patients with HLA-B27 associated ankylosing spondylitis than in healthy controls.
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PMID:IgA antibodies in HLA-B27 associated acute anterior uveitis and ankylosing spondylitis. 883 4

We examined 134 male patients with confirmed ankylosing spondylitis. The study protocol included a medical-rheumatological examination and thorough exploration for infections of the urinogential tract. An urethroadnexitis was found in 37 of 134 patients (27.6%): Two patients suffered from balanitis, 17 patients from urethritis, 18 patients from prostatitis, and two patients from epididymitis. Only four patients gave a history of urethritis and eight patients of prostatitis. The microorganisms isolated most frequently from patients with urogenital infection were Chlamydia trachomatis and, in few cases, Ureaplasma urealyticum. By comparing the urethroadnexitis group and the non-infected group with regard to other clinical parameters, we found a significantly increased C-reactive protein in the infected group. Other clinical parameters like involvement of the free spinal column, inflammatory involvement of the joints, and HLA-B27 correlation did not differ significantly.
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PMID:[Ankylosing spondylitis and urogenital infection: diagnosis of urologic infection and correlation with rheumatologic findings]. 896 85

Thirty-two female patients with confirmed ankylosing spondylitis (AS) and 33 women of similar age with pure ileitis terminalis Crohn were examined for genitourinary infection. Urethral syndrome was found in 15 out of 32 patients with AS: 11 of them had urethritis and 4 urethritis associated with vaginitis. Five women of the control group suffered from urethritis. In all cases with genitourinary infection, Chlamydia trachomatis was isolated. By comparing the AS-patients (urogenital infection group and the non-infected group) with regard to other present clinical parameters, it was found, as expected, that the erythrocyte sedimentation rate in the 1st hour was significantly higher in the infected group. In addition, the infected patients had a significantly higher incidence of enthesopathy, involvement of the spinal column, and higher C-reactive protein values (CRP > or = 5 mg/l). A family history of AS was equally present. Other clinical parameters, such as inflammatory involvement of the joints and HLA-B27 correlation, did not differ significantly between infected and non-infected patients.
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PMID:Ankylosing spondylitis and infections of the female urogenital tract. 954 78

In the pathogenesis of spondyloarthropathies, infection and gut inflammation are the most important external triggering factors. Early antimicrobial therapy to treat urethritis caused by Chlamydia trachomatis is effective in preventing a recurrent reactive arthritis. When the arthritis appear, a short term conventional antimicrobial therapy is unable to modify its course. In acute chlamydia arthritis, patients benefit from a prolonged (3-month) treatment with tetracycline, while such a treatment has not proved to be effective in enteroarthritis or in chronic forms of reactive arthritis. The role of sulfasalazine in the treatment of patients with spondyloarthropathies is controversial. It might modify the disease course during acute and chronic reactive arthritis, and is working for patients with ankylosing spondylitis, especially patients with peripheral arthritis. Data showing an effect of sulfasalazine in the prevention of chronic spondyloarthropathy or in modification of the long-term prognosis of ankylosing spondylitis are, however, lacking.
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PMID:Therapeutic aspects of spondyloarthropathies -- a review. 980 93

One hundred and thirty-four male and 32 female patients with ankylosing spondylitis and 33 women with pure ileitis terminalis Crohn were examined. The study protocol included a medical-rheumatological examination and thorough investigation for genitourinary infection. Urethroadnexitis was found in 37/134 male patients (2 patients suffered from balanitis, 17 patients from urethritis, 18 patients from prostatitis, and 2 patients from epididymitis), 15/32 female patients (11 of them had urethritis and in 4 cases urethritis associated with vaginitis) and 5/33 women with ileitis terminalis (every case with urethritis). The microorganism isolated most frequently from patients with genitourinary infection was Chlamydia trachomatis. The majority of patients with genitourinary infection were HLA-B27 positive. Nevertheless, the following conclusions can be reached: (1) evidence of Chlamydia trachomatis infection is frequent in male and female patients with ankylosing spondylitis, (2) patients with genitourinary infection tend to have HLA-B27, and (3) furthermore, presence of genitourinary infection was not significantly associated with chronic illness.
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PMID:Ankylosing spondylitis and genitourinary infection. 989 67

The association of HLA-B27 with ankylosing spondylitis and reactive arthritis is the strongest one known between an MHC class I Ag and a disease. We have searched the proteome of the bacterium Chlamydia trachomatis for HLA-B27 binding peptides that are stimulatory for CD8(+) cells both in a model of HLA-B27 transgenic mice and in patients. This was done by combining two biomathematical computer programs, the first of which predicts HLA-B27 peptide binding epitopes, and the second the probability of HLA-B27 peptide generation by the proteasome system. After preselection, immunodominant peptides were identified by Ag-specific flow cytometry. Using this approach we have identified for the first time nine peptides derived from different C. trachomatis proteins that are stimulatory for CD8(+) T cells. Eight of these nine murine-derived peptides were recognized by cytotoxic T cells. The same strategy was used to identify B27-restricted chlamydial peptides in three patients with reactive arthritis. Eleven peptides were found to be stimulatory for patient-derived CD8(+) T cells, of which eight overlapped those found in mice. Additionally, we applied the tetramer technology, showing that a B27/chlamydial peptide containing one of the chlamydial peptides stained CD8(+) T cells in patients with Chlamydia-induced arthritis. This comprehensive approach offers the possibility of clarifying the pathogenesis of B27-associated diseases.
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PMID:Identification of HLA-B27-restricted peptides from the Chlamydia trachomatis proteome with possible relevance to HLA-B27-associated diseases. 1159 5

HLA-B27 is strongly associated with spondyloarthropathies, including ankylosing spondylitis and reactive arthritis. The latter disease is triggered by various Gram-negative bacteria. A dodecamer derived from the intracytoplasmic tail of HLA-B27 was a natural ligand of three disease-associated subtypes (B*2702, B*2704, and B*2705) but not of two (B*2706 and B*2709), weakly or not associated to spondyloarthropathy. This peptide was strikingly homologous to protein sequences from arthritogenic bacteria, particularly to a region of the DNA primase from Chlamydia trachomatis. A synthetic peptide with this bacterial sequence bound in vitro disease-associated subtypes equally as the natural B27-derived ligand. The chlamydial peptide was generated by the 20 S proteasome from a synthetic 28-mer with the sequence of the corresponding region of the bacterial DNA primase. Molecular modeling suggested that the B27-derived and chlamydial peptides adopt very similar conformations in complex with B*2705. The results demonstrate that an HLA-B27-derived peptide mimicking arthritogenic bacterial sequences is a natural ligand of disease-associated HLA-B27 subtypes and suggest that the homologous chlamydial peptide might be presented by HLA-B27 on Chlamydia-infected cells.
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PMID:Molecular mimicry of an HLA-B27-derived ligand of arthritis-linked subtypes with chlamydial proteins. 1212 5

The strong association of the HLA class 1 allele HLA B27 with ankylosing spondylitis (AS) has been recognized for over 25 yr, however the pathogenic mechanism linking HLA B27 with AS and other spondyloarthropathies remains a mystery. We now know that the principal natural function of HLA B27 is an immunologic one, namely to bind antigenic peptides and then present them to T lymphocytes. I have shown that HLA B27 functions as an excellent antigen-presenting molecule in both spondyloarthropathy patients and healthy individuals. A working molecular model of how T cells recognize HLA B27 has been generated and tested. Evidence that T cells have a role in spondyloarthritis has also been found. First, expanded populations of T lymphocytes were found in both the blood and synovial fluid of patients with reactive arthritis (ReA). Secondly, a strong cytotoxic T-cell response to an HLA B27-restricted peptide epitope from Chlamydia trachomatis was found in a patient with ReA. This peptide, derived from a bacterium known to trigger ReA, is thus a candidate 'arthritogenic' peptide. We have also found evidence that HLA B27 has an unusual cell biology compared with other HLA molecules. HLA B27 demonstrates an unusual ability to form heavy chain homodimers in vitro. Dimerization is dependent upon disulphide bonding through an unpaired cysteine at position 67. Remarkably these dimers lack beta2 microglobulin, previously thought to be an essential component of all mature MHC class 1 molecules. HLA B27 homodimer formation has also been demonstrated in certain cell lines in vivo, and preliminary data suggest that significant numbers of T cells from patients with spondyloarthropathy express a ligand for HLA B27 homodimers. These findings have extended our understanding of the beneficial immunologic function of HLA B27, and have also led us to propose the testable new hypothesis that HLA B27 heavy chain dimerization may be involved in the pathogenesis of spondyloarthritis.
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PMID:HLA B27 in health and disease: a double-edged sword? 1215 2

Strictly speaking, "reactive arthritis" is a conventional term with no study-verified definition. This review will focus on the type of arthritis that is induced by the following species: Chlamydia, Shigella, Salmonella, Yersinia, and Campylobacter. The types of arthritis caused by these pathogens share a clinical pattern that is common in the spondyloarthropathies, especially undifferentiated spondyloarthropathy and Reiter's syndrome. All these diseases, including ankylosing spondylitis, must also share major pathogenetic pathways.
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PMID:Role of bacteria and HLA-B27 in the pathogenesis of reactive arthritis. 1263 98


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