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Query: UNIPROT:P01889 (ankylosing spondylitis)
 5,717 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Biological markers of inflammation are useful for the diagnosis and monitoring of inflammatory rheumatic diseases. The present study tested, whether serum amyloid A (SAA) could be used as a marker of inflammatory disease activity in ankylosing spondylitis (AS). In 72 patients with AS, the two valuable surrogate markers of disease activity, erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP), and an established clinical activity score (Bath Ankylosing Spondylitis Disease Activity Index, BASDAI) were correlated to the serum levels of SAA. It was found that SAA correlates well with ESR, CRP, and BASDAI. Because of its strong correlation, SAA seems to be an additional very useful disease activity marker. When used in diagnosis, and especially in monitoring of inflammation, further studies are required. Another interesting point of view is the described role of plasma SAA as a precursor of Amyloid A (AA) protein in secondary amyloidosis, a known complication in AS. In all probability, high circulating SAA levels are a predisposing indicator of disease activity.
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PMID:Serum amyloid A--an indicator of inflammation in ankylosing spondylitis. 1083 20

Abundantly expressed serum amyloid A (SAA) protein under chronic inflammatory conditions gives rise to insoluble aggregates of SAA derivatives in multiple organs resulting in reactive amyloid A (AA) amyloidosis, a consequence of rheumatoid arthritis, Crohn's disease, ankylosing spondylitis, familial Mediterranean fever, and Castleman's disease. An inflammation-responsive transcription factor, SAF (for SAA activating factor), has been implicated in the sustained expression of amyloidogenic SAA under chronic inflammatory conditions. However, its role in the pathogenesis of AA amyloidosis has thus far remained obscure. In this paper we have shown that SAF-1, a major member of the SAF family, is abundantly present in human AA amyloidosis patients. To assess whether SAF-1 is directly linked to the pathogenesis of AA amyloidosis, we have developed a SAF-1 transgenic mouse model. SAF-1-overexpressing mice spontaneously developed AA amyloidosis at the age of 14 mo or older. Immunohistochemical analysis confirmed the nature of the amyloid deposits as an AA type derived from amyloidogenic SAA1. Furthermore, SAF-1 transgenic mice rapidly developed severe AA amyloidosis in response to azocasein injection, indicating increased susceptibility to inflammation. Also, during inflammation SAF-1 transgenic mice exhibited a prolonged acute phase response, leading to an extended period of SAA synthesis. Together, these results provide direct evidence that SAF-1 plays a key role in the development of AA amyloidosis, a consequence of chronic inflammation.
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PMID:Inflammation-responsive transcription factor SAF-1 activity is linked to the development of amyloid A amyloidosis. 1688 22

Amyloidosis is a systemic disorder characterized by the extracellular tissue deposition of insoluble, toxic aggregates in bundles of beta-sheet fibrillar proteins. These deposits are typically identified on the bases of their apple-green birrefringence under a polarized light microscope after staining with Congo red, and by the presence of rigid, nonbranching fibrils 8 to 10 nm in diameter on electron microscopy. The type of amyloid fibril unit can be further defined by immunohistology or by immunoelectron microscopy. It has been described at least 25 different human protein precursors of amyloid fibrils, which will describe its corresponding amyloid disease. The most common types of amyloidosis are AL (primary) and AA (secondary) types; the former, is the most frequent and is due to deposition of proteins derived from immunoglobulin light chain fragments, occurring alone or in association with multiple myeloma. The later (AA), is caused by deposition of fibrils composed of fragments of the acute phase reactant serum amyloid A (SAA) and complicates chronic diseases with ongoing or recurring inflammation, namely; rheumatoid arthritis (RA), juvenile chronic polyarthritis, ankylosing spondylitis, familial periodic fever syndromes (Familial Mediterranean Fever), chronic infections and furthermore, some neoplasms (mainly renal cell carcinoma and Hodgkin's disease). Despite its less frequent association, some benign neoplasms can subsequently complicate to AA amyloidosis, therefore, an early diagnose and successful treatment may lead indeed, to regression of the amyloid disease. Herein, we present two cases of AA amyloidosis, both of them caused by 2 different benign neoplasms: 1. A 34 year-old woman, after chronic oral contraceptive use, developed an hepatic adenoma (fig. 1) which finally lead to AA amyloidosis with primary kidney presentation (pure nephrotic syndrome) (table 1). Post-surgical complications yield to acute renal failure from which unfortunately could not be recovered. After being on hemodialysis therapy during 10 months she received a first renal allograft without any complication. 2. A 20 year old woman, was diagnosed of AA amyloidosis after a renal biopsy (fig. 2) because of nephrotic syndrome (table 1). Further investigation lead to the finding of a hialyne-vascular type Castleman's disease located in the retroperitoneum (fig. 2). Despite surgical resection and medical treatment (colchicine) she developed progressive renal failure requiring initialization of hemodialysis therapy. After 6 years being on hemodialysis, she received a first renal allograft which is currently functioning after one year of follow- up. Although other chronic inflammatory diseases complicate more frequently to AA amyloidosis, benign tumors have to be taken into account as a potential ethiological cause for secondary amyloidosis.
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PMID:[Systemic AA amyloidosis induced by benign neoplasms]. 1833 38

Secondary (AA) amyloidosis is a disease that is caused by systemic deposition of amyloid fibrils. Circulating serum amyloid A protein is an acute phase reactant and levels are therefore high during inflammatory states. Chronic elevation of serum amyloid A levels results in accumulation and deposition in various organs, leading to organ dysfunction. Unless the inciting inflammatory state can be controlled, the subsequent development of amyloidosis diminishes patient survival. We report a case of systemic amyloidosis that presented primarily as chronic diarrhea in a patient with ankylosing spondylitis. Unfortunately for the patient, the diagnosis of amyloidosis was delayed for years despite encounters with multiple physicians. Early medical intervention to control chronic inflammation is imperative and could prevent morbidity and mortality related to the development of secondary amyloidosis. Consideration of amyloidosis as a diagnosis in patients who have chronic uncontrolled inflammatory conditions is also important in preventing poor outcomes related to this disease.
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PMID:Systemic amyloidosis presenting as chronic diarrhea in a patient with ankylosing spondylitis. 2005 51

Systemic AA amyloidosis is a long-term complication of several chronic inflammatory disorders, including rheumatoid arthritis, ankylosing spondylitis, autoinflammatory syndromes, Crohn's disease, malignancies and conditions predisposing to recurrent infections. Organ damage results from the extracellular deposition of proteolytic fragments of the acute-phase reactant serum amyloid A (SAA) as amyloid fibrils. A sustained high concentration of SAA is the prerequisite for developing AA amyloidosis. However, only a minority of patients with long-standing inflammation actually presents with this complication, pointing to the existence of disease-modifying factors, the best characterised of which being SAA1 genotype. The kidneys, liver and spleen are the main target organs of AA amyloid deposits. In more than 90% of patients proteinuria, nephrotic syndrome and/or renal dysfunction dominate the clinical picture at onset. If not effectively treated, this disease invariably leads to end stage kidney disease and renal replacement therapy, that are still associated with a poor outcome. Although the incidence of AA in rheumatoid arthritis and other chronic arthritides has continuously decreased over the past ten years, thanks to the increasing availability of more effective anti-inflammatory and immunosuppressive therapies, AA remains a life-threatening disease with several areas of uncertainty and unmet needs, deserving continuous efforts at prevention and effective treatment. The deeper understanding of the molecular mechanisms of amyloid formation and regression is now driving the development of novel treatments targeting different steps in the amyloidogenic cascade. These therapies will hopefully improve the quality of life and outcome of these patients in a near future.
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PMID:AA amyloidosis: basic knowledge, unmet needs and future treatments. 2265 7