Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0519030 (Klebsiella)
21,988 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Acute anterior uveitis (AAU) is characterized by sudden-onset, mostly unilateral exacerbations of an inflammation of the iris and ciliary body. The duration of illness is short if the patient is treated with corticosteroids. Half of all patients with any type of anterior uveitis are HLA-B27-positive, and more than half of the B27-positive patients have spondyloarthropathy. Ophthalmologists should therefore refer all patients with AAU who are HLA-B27-positive to a rheumatologist. Because attacks of AAU are extremely painful and frightening, most spondyloarthropathy patients with AAU will seek out an ophthalmologist on their own. The anterior chamber of the eye and the joints are mesenchymal cavities that are cleaned by macrophages. Anterior chamber-associated immune deviation is the mechanism by which specific regulatory T cells normally produce sufficient transforming growth factor-beta to impair inflammatory reactions that might hamper vision. Another mechanism of immune privilege is Fas-ligand induced apoptosis. Because the cells of the anterior eye express Fas-ligand, infiltrating cells are apoptotically killed. Comparable mechanisms may occur at a lower level in joints. The cause of AAU and spondyloarthropathy is unknown. B27 is probably only responsible for one quarter of the pathogenesis, other non-B27 genetic factors for another quarter, and unknown exogenous factors for the remaining half. It is possible that Gram-negative bacteria such as Klebsiella or Yersinia are involved in the pathogenesis in a yet unknown way.
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PMID:Acute anterior uveitis and spondyloarthropathies. 972 92

The etiopathogenesis of ankylosing spondylitis is still incompletely understood. HLA-B27 is important as more than 90% of the patients possess the antigen, but how this genetic marker confers disease susceptibility is yet to be understood. Recent studies of families and twins affected by ankylosing spondylitis have shown that additional non-HLA-B27 genes are necessary for disease development. The exogenous agent initiating chronic inflammation is yet to be identified, but Klebsiella pneumoniae remains a candidate. The microorganism may act through the intestinal canal as more than 60% of the patients exhibit inflammatory changes in the bowel.
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PMID:[Pathogenesis of Bechterew disease]. 988 41

Klebsiella is suggested to trigger ankylosing spondylitis (AS) and acute anterior uveitis (AAU) in HLA-B27-positive individuals. Previous investigations showed an increased antibody response to the Klebsiella capsular types K26, K36, and K50 in sera from HLA-B27-positive AS patients. In the present study the prevalence and titers of antibodies against Klebsiella capsular antigens were measured by means of an ELISA in 32 sera from HLA-B27-positive AAU patients either with (n = 10) or without AS (n = 22) and compared with sera from HLA-B27-negative AS-patients (n = 13). Sera from either HLA-B27-positive (n = 45) or negative (n = 40) healthy individuals served as control. Sera from HLA-B27-positive AAU with or without AS showed significantly higher antibody prevalence and IgG-titers against capsular antigens of the Klebsiella serotypes K26, K36, and K50 when compared with sera from HLA-B27-negative AS patients or with healthy controls. These results might be taken to indicate the predominance of these serotypes in the HLA-B27-associated AS and AAU.
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PMID:Humoral immune response to Klebsiella capsular polysaccharides in HLA-B27-positive patients with acute anterior uveitis and ankylosing spondylitis. 989 2

A study was made of antibodies to some enterobacteria--potential triggers of spondyloarthropathies in population of mordva characterized by higher frequency of HLA-B27. 141 and 148 plasm samples were taken from erzya and moksha subpopulations, respectively. Enzyme immunoassay has detected specific antibodies IgA, IgM, IgG to Salmonella, Yersinia, Campylobacter and Klebsiella. Specific immune response in the mordva population appeared to depend on gender, age and nationality but not HLA-B27. In the study population the role of Klebsiella infection in development of ankylosing spondylarthritis was not confirmed though the number of the patients was not sufficient to reject this suggestion.
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PMID:[Population-based study of antibodies to certain potential infectious triggers of spondylarthropathies: a study of Ugro-Finnish population of Russia]. 1056 Feb 52

It has been well established that many diseases are linked to HLA antigens. Two of the most interesting HLA associations may provide some insight into the pathogenesis of rheumatic inflammatory conditions. In ankylosing spondylitis (AS), 96% of patients possess HLA-B27, whilst the frequency of this marker in the general population is c. 8%. In rheumatoid arthritis (RA), >90% of patients possess either HLA-DR1 or some subtypes of HLA-DR4, whilst the frequency of this marker in the general population is c. 35%. The association between HLA-B27 and reactive arthritis (ReA) has also been well established. Furthermore, it has been shown that ReA is triggered by infection via the gastrointestinal tract due to Yersinia, Salmonella or Campylobacter spp. and in the genitourinary tract due to chlamydia. In a similar way, microbiological and immunological studies have revealed an association between Klebsiella pneumoniae in AS and Proteus mirabilis in RA. This article reviews the possible pathological implications of the associations between HLA-B27, K. pneumoniae and AS, as well as HLA-DR1/DR4, P. mirabilis and RA.
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PMID:HLA molecules, bacteria and autoimmunity. 1075 23

Crohn's disease (CD) is an immune-mediated gastrointestinal inflammatory disease, which could arise from an interplay between genetic and environmental factors. Klebsiella microbes were suggested to have a vital role in the initiation and perpetuation of the disease through the mechanism of molecular mimicry. This proposition is based on the results of various studies where significantly elevated levels of antibodies against the whole bacteria or preparations from Klebsiella microbes and antibodies to collagen types I, III, IV, and V were detected in patients with CD and patients with ankylosing spondylitis (AS). Molecular similarities were found between Klebsiella nitrogenase and HLA-B27 genetic markers and between Klebsiella pullulanase and collagen fibers types I, III, and IV. Furthermore, significantly positive correlations and cross-reactivity binding activities were observed between anti-Klebsiella and anticollagen antibodies among patients with CD and AS. Early treatment of CD patients with anti-Klebsiella measures is proposed, which may involve the use of antibiotics and low starch diet together with other traditionally used immunomodulatory, immunosuppressive, or biologic agents.
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PMID:A possible link between Crohn's disease and ankylosing spondylitis via Klebsiella infections. 1694 Dec 2

"B27 disease" is a new autoimmune disease that afflicts millions of people throughout the world. "B27 disease" occurs in individuals who have ankylosing spondylitis (AS) or preankylosing spondylitis and/or uveitis and are also positive for HLA-B27. Molecular mimicry between the bowel microbe Klebsiella and the HLA-B27 molecule, as well as the spinal collagens types I, III, and IV, indicates a pathological mechanism involving autoimmunity. Antibodies to Klebsiella microbes have been reported in AS patients from 18 different countries. Sera from patients with AS show complement-dependent cytopathic activity against sheep red cells coated with HLA-B27 peptide antigens. Diagnosis of B27 disease can lead to early treatment, involving low-starch diet, sulfasalazine, and immunosuppressive and biological agents so as to prevent the irreversible bony changes of established classical AS. The concept of B27 disease provides a new approach to the study and treatment of these disorders and needs to be evaluated in prospective studies by the world rheumatological community.
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PMID:B27 disease is a new autoimmune disease that affects millions of people. 1791 26

HLA-B27 positive individuals are predisposed to reactive arthritis developing 1-3 weeks after urogenital and gastrointestinal infections. Also ankylosing spondylitis (AS) associates strongly to HLA-B27, but no specific infection, Klebsiella pneumoniae excluded, has been linked to it. Before the discovery of its HLA-B27 association there were many reports suggesting a link between chronic prostatitis in men or pelvic inflammatory disease in women and AS. They have since been forgotten although HLA-B27 did not help to understand, why this disease has an axial and ascending nature. It is proposed that the urogenital organs form a source of damage (or danger)-associated molecular patterns (DAMPs), either exogenous pathogen-associated molecular patterns (PAMPs) from microbes or endogenous alarmins, such as uric acid, released from necrotic cells or urate deposits. DAMPs are slowly seeded from low-down upwards via the pelvic and spinal lymphatic pathways. They reach Toll-like receptors (TLRs) in their target mesenchymal stem cells, which are stimulated to ectopic enchondral bone formation leading to syndesmophytes and bamboo spine. At the same time inflammatory cytokines induce secondary osteoporosis of the spine. This new paradigm places microbes, HLA-B27 and TLRs in the pathogenic centre stage, but without pinpointing any (one) specific pathogen; instead, shared microbial patterns are indicated.
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PMID:Microbial antigens mediate HLA-B27 diseases via TLRs. 1929 8

Crohn's disease is suggested to result from a microbially triggered immune-mediated autoimmune process, involving mainly the terminal ileum and ileo-caecal junction. Klebsiella pneumoniae shares certain molecular structures present in pullulanase pulA and pulD secretion enzymes with various self-antigens present in collagens and HLA-B27 molecules, respectively. A link exists between high dietary starch intake and the growth of intestinal microflora, involving especially Klebsiella microbes. Increased exposure to Klebsiella in the gut as the result of high starch intake would lead to high production of antiKlebsiella antibodies as well as autoantibodies to the cross-reactive self-antigens with the resultant inflammation at the pathological sites. Eradication of these microbes from the gut in patients with Crohn's disease with the use of low-starch diet and antibacterial agents as well as immunomodulatory measures could be beneficial in the management of this disease.
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PMID:Role of Klebsiella and collagens in Crohn's disease: a new prospect in the use of low-starch diet. 1935 92

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 the Klebsiella microbes in the bowel. Exposure to increased levels of these microbes will lead to the production of elevated levels of anti-Klebsiella antibodies 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.
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PMID:The link between ankylosing spondylitis, Crohn's disease, Klebsiella, and starch consumption. 2378 Dec 54


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