Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0003864 (arthritis)
 69,039 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

SAA1 is the predominant isoform of acute phase human SAA deposited as AA amyloid fibrils in reactive systemic amyloidosis. It has recently been reported that in the Japanese population, in whom the SAA1 gamma allele occurs with a frequency of 37%, possession of, and especially, homozygosity for this allele is a significant risk factor for AA amyloidosis in adult patients with rheumatoid arthritis (RA). In contrast we report here that in a control sample of 95 healthy adult male Caucasians the SAA1 gamma allele occurs at the much lower frequency of 5.3% and that, among 41 patients with juvenile chronic arthritis (JCA) and AA amyloidosis, there was a highly significantly increased frequency of the SAA1 alpha allele (90.2%), and particularly homozygosity for this allele (80.5%), compared both to the healthy controls (75.8% and 57.9% respectively) and to 8 JCA cases without amyloid (56.3% and 12.5%). A similar trend with respect to frequency of the SAA1 alpha allele and homozygosity for it was observed among 26 adult Caucasian RA patients with AA amyloid and 26 such cases without amyloid, although it did not reach statistical significance. These results suggest that there is probably differential amyloidogenicity amongst the different SAA1 isoforms and indicate that homozygosity for SAA1 alpha and SAA1 gamma in the different populations is a significant risk factor for development of AA amyloidosis. In Caucasian patients with JCA, the presence of the homozygous SAA1 alpha genotype indicates high risk of amyloidosis and should encourage early and aggressive anti-inflammatory therapy to keep circulating SAA levels as low as possible.
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PMID:SAA1 alleles as risk factors in reactive systemic AA amyloidosis. 1003 84

The acute-phase reactant rabbit serum amyloid A 3 (SAA3) was identified as the major difference product in Ag-induced arthritis in the rabbit, a model resembling in many aspects the clinical characteristics of rheumatoid arthritis (RA) in humans. In Ag-induced arthritis, up-regulated SAA3 transcription in vivo was detected in cells infiltrating into the inflamed joint, in the area where pannus formation starts and, most notably, also in chondrocytes. The proinflammatory cytokine IL-1beta induced SAA3 transcription in primary rabbit chondrocytes in vitro. Furthermore, rSAA3 protein induced transcription of matrix metalloproteinases in rabbit chondrocytes in vitro. In the human experimental system, IL-1beta induced transcription of acute-phase SAA (A-SSA; encoded by SAA1/SAA2) in primary chondrocytes. Similar to the rabbit system, recombinant human A-SAA protein was able to induce matrix metalloproteinases' transcription in chondrocytes. Further, immunohistochemistry demonstrated that A-SAA was highly expressed in human RA synovium. A new finding of our study is that A-SSA expression was also detected in cartilage in osteoarthritis. Our data, together with previous findings of SAA expression in RA synovium, suggest that A-SAA may play a role in cartilage destruction in arthritis.
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PMID:Serum amyloid A (apoSAA) expression is up-regulated in rheumatoid arthritis and induces transcription of matrix metalloproteinases. 1116 Mar 47

Differential proteome analysis is used to study body fluids from patients suffering from rheumatoid arthritis (RA), reactive arthritis (reaA) or osteoarthritis (OA). Mass spectrometric structure characterization of gel-separated proteins provided a detailed view of the protein-processing events that lead to distinct protein species present in the respective body fluids. (i) Fibrin(ogen) beta-chain degradation products, presumably plasmin-derived, appeared solely in synovial fluids (SF) from both patient collectives, (ii) calgranulin B (MRP14) was exclusively identified in SF samples derived from 5 out of 6 patients suffering from RA. Calgranulin B was not observed in synovial fluids from OA patients, nor in plasmas from either patient group. In all cases where calgranulin B was detected, calgranulin C was identified as well. (iii) Serum amyloid A protein spots were determined in plasmas and synovial fluids from patients with RA, but not in patients with OA. In addition to disease-relevant differences, interindividual differences in haptoglobin patterns of the patients under investigation were observed. Hence, in-depth proteome analysis of body fluids has proven effective for identification of multiple molecular markers and determination of associated protein structure modifications, that are thought to play a role for specifically determining a defined pathological state of diseased joints.
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PMID:Mass spectrometric proteome analyses of synovial fluids and plasmas from patients suffering from rheumatoid arthritis and comparison to reactive arthritis or osteoarthritis. 1237 75

Familial Mediterranean fever (FMF) is an autosomal recessive disease, which primarily affects the population surrounding the Mediterranean basin. It is characterized by recurrent attacks of fever and peritonitis, pleuritis, arthritis or erysipelas-like erythema. Amyloidosis, causing renal failure, is one of the most severe complications of the disease. The gene associated with FMF (MEFV) has been recently isolated. Phenotype-genotype correlation studies revealed that amyloidosis was more common in FMF patients originating from North-Africa who were homozygous for the M694V mutation. Such a correlation was not found in Turkish patients. The risk of amyloidosis is increased in male FMF patients and in patients bearing polymorphism a/a in the SAA1 gene. Colchicine is the chosen drug for the treatment of FMF and can prevent amyloidosis.
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PMID:Familial Mediterranean fever (FMF) and renal AA amyloidosis--phenotype-genotype correlation, treatment and prognosis. 1283 47

Familial Mediterranean fever (FMF) is the most frequent periodic syndrome characterized by recurrent attacks of polyserositis. Fever, abdominal pain, chest pain, and arthritis/arthralgia are the leading symptoms. It is an autosomal recessive disorder, which primarily affects Jewish, Armenian, Turkish, and Arab populations. The FMF gene ( MEFV) has recently been cloned to chromosome 16p, which encodes pyrin. Genotype-phenotype correlation is not well established. Amyloidosis is the most severe complication of FMF. The SAA1-alpha/alpha genotype was associated with an increased risk of amyloidosis. Colchicine treatment not only decreases the frequency and severity of attacks, but also prevents amyloidosis. Certain vasculitides, namely Henoch-Schonlein purpura and polyarteritis nodosa, are more frequent among FMF patients.
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PMID:Familial Mediterranean fever. 1283 90

Familial Mediterranean Fever (FMF), also known as paroxysmal polyserositis, is an autosomal recessive disease affecting mainly Mediterranean populations (Jews, Armenians, Arabs, Turks). It is characterised by recurrent crises of fever and serosal inflammation, leading to abdominal, thoracic or articular pain. Erysipela-like erythema affecting mainly feet and legs and effort-induced myalgia are less frequently encountered symptoms. The major complication of FMF is the development of renal amyloidosis. Standard laboratory tests of FMF patients are non-informative, except for the high sedimentation rate and white blood cell count, but during and immediately after crises, diminished albumin concentrations and elevated fibrinogen, C-reactive protein, beta2 and alpha2 M globulins, haptoglobin and lipoprotein concentrations are noted. Studies have measured immunoglobulin (Ig) levels in the sera of FMF patients and found elevated levels of IgA, IgM, IgG, and IgD in 23%, 13%, 17% and 13%, respectively. FMF crises are characterised by a massive influx of polymorphonuclear leukocytes into the inflamed regions. Moreover, the peritoneal fluid of FMF patients contains abnormally low levels of the inhibitor of complement fragment C5a and interleukin 8. Failure to suppress inflammatory response to C5a may explain the typical inflammatory FMF crises. The MEFV (for MEditerranean FeVer) gene responsible for the disease has been identified on 16p13.3. It is composed of 10 exons and spans approximately 14 Kb of genomic DNA. More than 35 mutations have so far been identified. The most frequent are M694V, M694I, M680I, V726A and E148Q. The M694V mutation is the most frequent mutation in the various ethnic groups considered, although its frequency varies from group to group. The V726A mutation is observed mainly among Ashkenazi and Iraqi Jews, Druzes and Armenians, and the M680I among Armenians and Turks. M694I and A744S seem specific to Arab populations, and R761H is frequently found in Lebanese FMF patients. The M694V mutation is often correlated with severe phenotypes, mainly in the homozygous state. It has been specifically correlated with arthritis, pleuritis and especially amyloidosis. Patients with other mutations in the 694 and 680 codons can also have severe phenotypes. The V726A mutation, although identified in FMF patients with a relatively mild phenotype, has also been detected in patients with renal amyloidosis. E148Q is often associated with a mild phenotype, and whether it is even a polymorphism has been questioned. The MEFV gene codes for a protein that was respectively called pyrin and marenostrin by the French and international consortia that simultaneously identified the gene. Its function is still not determined, but it was recently colocalised with microtubules and actin filaments in the cytoplasm. It contains a death domain called PYD (Pyrin Domain), usually associated with proteins involved in apoptosis. Some genes have been tested to assess their possible modifying effects on clinical features of FMF. The alpha/alpha genotype of the serum amyloid A or SAA1 gene is associated with an increased risk of amyloidosis in FMF patients, especially in patients homozygous for M694V, whereas the MICA (Major Histocompatibility Complex, MHC class-I-chain-related type A) gene seems to have an effect on disease course but not its clinical manifestations. The most effective treatment for FMF patients is colchicine, which should be taken regularly on a life-long basis. It decreases the frequency and severity of crises and prevents renal amyloidosis.
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PMID:[Familial Mediterranean Fever (FMF): from diagnosis to treatment]. 1574 78

Most notable among the acute phase proteins is serum amyloid A (SAA), levels of which can increase 1000-fold during infections, aseptic inflammation, and/or trauma. Chronically elevated SAA levels are associated with a wide variety of pathological conditions, including obesity and rheumatic diseases. Using a recombinant hybrid of the two human SAA isoforms (SAA1 and 2) that does not exist in vivo, numerous in vitro studies have given rise to the notion that acute phase SAA is a pro-inflammatory molecule with cytokine-like properties. It is however unclear whether endogenous acute phase SAA per se mediates pro-inflammatory effects. We tested this in samples from patients with inflammatory arthritis and in a transgenic mouse model that expresses human SAA1. Endogenous human SAA did not drive production of pro-inflammatory IL-8/KC in either of these settings. Human neutrophils derived from arthritis patients displayed no signs of activation, despite being exposed to severely elevated SAA levels in circulation, and SAA-rich sera also failed to activate cells in vitro. In contrast, two recombinant SAA variants (the hybrid SAA and SAA1) both activated human neutrophils, inducing L-selectin shedding, production of reactive oxygen species, and production of IL-8. The hybrid SAA was approximately 100-fold more potent than recombinant SAA1. Recombinant hybrid SAA and SAA1 activated neutrophils through different receptors, with recombinant SAA1 being a ligand for formyl peptide receptor 2 (FPR2). We conclude that even though recombinant SAAs can be valuable tools for studying neutrophil activation, they do not reflect the nature of the endogenous protein.
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PMID:Endogenous Acute Phase Serum Amyloid A Lacks Pro-Inflammatory Activity, Contrasting the Two Recombinant Variants That Activate Human Neutrophils through Different Receptors. 2362 89

Serum amyloid A (SAA) is an acute-phase response protein in the liver, and SAA1 is the major precursor protein involved in amyloid A amyloidosis. This amyloidosis has been reported as a complication in chronic inflammatory conditions such as arthritis, lupus, and Crohn's disease. Obesity is also associated with chronic, low-grade inflammation and sustained, elevated levels of SAA1. However, the contribution of elevated circulating SAA1 to metabolic disturbances and their complications is unclear. Furthermore, in several recent studies of transgenic (TG) mice overexpressing SAA1 that were fed a high-fat diet (HFD) for a relatively short period, no relationship was found between SAA1 up-regulation and metabolic disturbances. Therefore, we generated TG mice overexpressing SAA1 in the liver, challenged these mice with an HFD, and investigated the influence of elevated SAA1 levels. Sustained, elevated levels of SAA1 were correlated with metabolic parameters and local cytokine expression in the liver following 16 weeks on the HFD. Moreover, prolonged consumption (52 weeks) of the HFD was associated with impaired glucose tolerance and elevated SAA1 levels and resulted in systemic SAA1-derived amyloid deposition in the kidney, liver, and spleen of TG mice. Thus, we concluded that elevated SAA1 levels under long-term HFD exposure result in extensive SAA1-derived amyloid deposits, which may contribute to the complications associated with HFD-induced obesity and metabolic disorders.
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PMID:Serum amyloid A1 levels and amyloid deposition following a high-fat diet challenge in transgenic mice overexpressing hepatic serum amyloid A1. 2721 80