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

The mechanism by which HLA-B27 confers genetic susceptibility to the seronegative spondyloarthropathies ankylosing spondylitis, Reiter's syndrome, and reactive arthritis, is not well understood. The current concept of an extraarticular bacterial infection functioning as the triggering event in a genetically susceptible host suggests the possibility of direct microbial-MHC interaction. We have addressed the role of HLA-B27 in microbial-host cell interaction by examining invasion by putatively arthritogenic gram-negative bacteria. Target cells used were murine L cells transfected with HLA-B27, HLA-A3, HLA-A2, HLA B44, HLA B18, or pSV2neo vector alone. Relative to the pSV2neo control and the HLA-A3 transfectant, HLA-B27-transfected cells demonstrated a consistent decrease in invasion for each of the following pathogens: Salmonella typhimurium (45 +/- 2% decrease), Shigella sonnei (53 +/- 13% decrease), Shigella flexneri (45 +/- 5% decrease), and enteroinvasive Escherichia coli (57 +/- 8% decrease). This decrease was specific for the HLA B27-transfected L cells and was not observed in the other B allele transfectants. The decreased invasion in the HLA-B27 transfectants is not the result of either altered endogenous mouse class I expression as a result of human class I transfection or increased intracellular bacterial killing within the B27 transfectants. There was an inverse relationship between the amount of surface expression of HLA-B27, as measured by FACS, and the degree of invasion. Blocking of surface B27 Ag with anti-B27 mAb augmented bacterial invasion in the B27 transfectants. These studies demonstrate a novel bacterial-B27 interaction that may have relevance to the pathogenesis of B27-related arthritis.
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PMID:HLA-B27 expression modulates gram-negative bacterial invasion into transfected L cells. 158 45

Microheterogeneity of acute phase proteins frequently differs in acute and chronic types of inflammation. However, it is unknown whether these changes depend on the duration of the inflammation in a given disease. We therefore investigated the microheterogeneity of alpha 1-acid glycoprotein (AGP) in sera from patients with acute and chronic bacterial infection in comparison to rheumatoid arthritis and ankylosing spondylitis. In acute bacterial infection Con A-reactivity of AGP was significantly elevated. By contrast, AGP in chronic bacterial infection showed the same glycosylation pattern as rheumatoid arthritis and ankylosing spondylitis being characterized by a decreased reactivity to Con A. Serial measurements in individual patients with bacterial infections showed a transition from the initially elevated to decreased reactivity to Con A as the disease became chronic.
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PMID:Glycosylation of alpha 1-acid glycoprotein in relation to duration of disease in acute and chronic infection and inflammation. 177 91

Several MHC (major histocompatibility complex) genes are associated with increased incidence of disease. The strongest association is between the class I gene, HLA-B27, and ankylosing spondylitis (AS). HLA-B27 is also highly associated with Reiter's syndrome. As not all subjects with HLA-B27 develop AS or Reiter's syndrome, environmental factors may have a key role in the pathogenesis of these arthritic diseases. Several studies have implicated klebsiella in the development of AS, whereas Reiter's syndrome may result from infection with yersinia, shigella, salmonella, campylobacter, or chlamydia. Transgenic mice present a unique opportunity to study the association of specific MHC genes and disease. HLA-B27 transgenic mice were produced to study the association of HLA-B27, bacterial infection, and arthritic disease. Mice with the HLA-B27 gene are more susceptible to intravenous infection with Yersinia enterocolitica 0:8 WA than negative litter mates as shown by a higher incidence of spinal abscesses and mortality. Understanding the mechanism(s) responsible for this difference may yield valuable insights into the pathogenesis of HLA-B27 associated disease in humans.
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PMID:Role of enterobacteria and HLA-B27 in spondyloarthropathies: studies with transgenic mice. 211 64

Multiple myeloma has rarely been reported in patients with ankylosing spondylitis. We observed a patient with a 20-year history of ankylosing spondylitis, who subsequently developed IgA myeloma. This association may not be simply coincidental. It has been proposed that the protracted stimulation of immunocytes by inflammatory lesions on the mucosal surfaces of the gastrointestinal, respiratory, and biliary tracts, where lymphocytes are already committed to IgA production, may be implicated in the pathogenesis of IgA myeloma in some patients. Ankylosing spondylitis is a chronic inflammatory disease, probably resulting from the interaction of a genetic predisposition involving HLA-B27 with an environmental event such as enteric bacterial infection. We propose that ankylosing spondylitis and IgA myeloma occurring concomitantly in our patient implies a possible pathogenetic relationship. In ankylosing spondylitis, persistent reticuloendothelial stimulation, due to chronic subclinical gastrointestinal infection, may lead to IgA-producing plasma cell activation and proliferation, and subsequent IgA myeloma development.
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PMID:Association of ankylosing spondylitis with IgA-multiple myeloma: report of a case and pathogenetic considerations. 280 65

Sacroiliac involvement is an early hallmark, but even so, patients with ankylosing spondylitis present a remarkable spectrum of disease. Research probing associations among spondylitis, enteric bacterial infection, and host expression of HLA-B27 may offer etiologic clues and point the way to disease-specific therapies.
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PMID:The spectrum of ankylosing spondylitis. 760 96

The polymorphism of HLA-B27 alleles is located in the peptide-anchoring motif. In recent years, fundamental insights have been made into the molecular aspects of HLA-B27-restricted presentation. Subtle differences in peptide binding fine specificity are especially interesting for closely related HLA-B27 alleles that have differential association with ankylosing spondylitis. Bacterial infection has been suggested to play a role in the pathogenesis of HLA-B27-associated disease. Remarkable progress has been made in identifying peptides derived from bacteria that can be presented by HLA-B27. Despite the mechanisms proposed to explain B27-associated diseases, there are no clear correlations between peptide sequence, differential binding to B27 subtypes, and recognition by peptide-specific T cell receptors. Furthermore, new transgenic models have now been developed that we hope will allow a clearer view of the function of B27 and the mechanisms involved in the pathogenesis of spondyloarthropathies.
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PMID:HLA-B27 structure, function, and disease association. 886 80

Reactive arthritis (ReA) occurs after a preceding bacterial infection of the urogenital or gastroenteral tract. The bacteria triggering ReA persist in vivo and seem to be responsible for triggering an immune response. A cytokine imbalance with a relative lack of T-helper 1 cytokines may play an important role allowing these bacteria to survive. This seems to be relevant for manifestation and chronicity of the arthritis. For the chronic cases and cases evolving into ankylosing spondylitis, the interaction between bacteria and human leukocyte antigen B27 plays an additional crucial role. Among others, the arthritogenic peptide hypothesis is one way to explain this association. Human leukocyte antigen B27-restricted peptides from Yersinia and Chlamydia, which are stimulatory for CD8+ T cells derived from patients with ReA, have been identified. The exact role of such peptides for the pathogenesis of ReA and other spondyloarthritides still has to be defined.
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PMID:Disease mechanisms in reactive arthritis. 1501 41

The spondyloarthritides (SpA) are often included in the differential diagnosis of early arthritis with or without low back pain. This is namely true for reactive arthritis which occurs as acute or subacute arthritis in association with urogenital or gastrointestinal bacterial infection. Reactive arthritis can result in chronic or relapsing disease. The SpA group also includes ankylosing spondylitis (axial form or with peripheral arthritis), psoriatic arthritis and SpA in association with inflammatory bowel disease. (Early) undifferentiated SpA has now come into the focus of many researchers since more effective and specific therapy has become available for the SpA. Diagnostic algorithms have been developed and evaluated.
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PMID:[Early spondyloarthritis]. 1826 56

Tumor necrosis factor-alpha (TNF-alpha) was first isolated two decades ago as a macrophageproduced protein that can effectively kill tumor cells. TNF-alpha is also an essential component of the immune system and is required for hematopoiesis, for protection from bacterial infection and for immune cell-mediated cytotoxicity. Extensive research, however, has revealed that TNF-alpha is one of the major players in tumor initiation, proliferation, invasion, angiogenesis and metastasis. The proinflammatory activities link TNF-alpha with a wide variety of autoimmune diseases, including psoriasis, inflammatory bowel disease, rheumatoid arthritis, systemic sclerosis, systemic lupus erythematosus, multiple sclerosis, diabetes and ankylosing spondylitis. Systemic inhibitors of TNF such as etanercept (Enbrel) (a soluble TNF receptor) and infliximab (Remicade) and adalimumab (Humira) (anti-TNF antibodies) have been approved for the treatment inflammatory bowel disease, psoriasis and rheumatoid arthritis. These drugs, however, exhibit severe side effects and are expensive. Hence orally active blockers of TNF-alpha that are safe, efficacious and inexpensive are urgently needed. Numerous products from fruits, vegetable and traditional medicinal plants have been described which can suppress TNF expression and TNF signaling but their clinical potential is yet uncertain.
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PMID:Targeting TNF for Treatment of Cancer and Autoimmunity. 1976 65