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)

A seropositive white man had follow-up for 16 years with a diagnosis of palindromic rheumatism. Treatment had included parenteral gold, methotrexate, prednisone, hydroxychloroquine sulfate, and penicillamine before diarrhea led to a biopsy-proven diagnosis of Whipple's disease. Clinical and radiographic criteria for ankylosing spondylitis were met. In addition to classic Whipple's arthropathy, he had the combined but singular findings of pancarpal destruction and cervical apophyseal fusion. HLA typing revealed the B7 antigen. This case illustrates the pitfalls in diagnosis of a chronic polyarthritis that has, as a typical feature, a long latency before manifesting its more specific signs and symptoms (ie, diarrhea, malabsorption, and hyperpigmentation). Care should be taken during evaluation of any disease with atypical and nonspecific features (eg, positive rheumatoid factor in a patient with polyarthritis) and one should continue to reevaluate the original impression while confirmatory evidence is lacking. Moreover, the roentgenographic findings of pancarpal narrowing, apophyseal fusion, and advanced iliofemoral joint disease, in addition to sacroiliitis and syndesmophyte formation, challenge the generally held notion that Whipple's arthropathy is a nondestructive joint disease.
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PMID:Whipple's disease with axial and peripheral joint destruction. 169 47

Three T-cell lines and clones of the OKT4 phenotype have been isolated from the peripheral blood of three patients with ankylosing spondylitis. Antigen specificities of T cells were determined with purified protein derivative-(PPD) and cartilage-derived antigens, namely proteoglycans from human articular cartilage and intervertebral disc, bovine nasal cartilage, and rat chondrosarcoma and human type II collagen from cartilage. A cell line from one patient reacted with proteoglycans from human articular cartilage and human intervertebral disc, but the other two cell lines (each from a different patient) and four clones from one of the latter two lines proved to be highly specific for the human articular cartilage proteoglycan. From a study of four proteoglycan specific clones isolated from one patient, it is clear that removal of chondroitin sulfate had no effect on immunoreactivity but digestion of proteoglycan with pronase or alkali/sodium borohydride treatment abolished all reactivity. A OKT4-positive T-cell clone isolated from a healthy adult which was reactive to PPD was used to compare the antigen specificity of cells: this clone showed no reactivity to any of the other putative antigens listed above.
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PMID:Isolation of proteoglycan-specific T lymphocytes from patients with ankylosing spondylitis. 244 81

Intraperitoneal injection of human fetal cartilage proteoglycan (depleted of chondroitin sulfate) in Freund's complete or incomplete adjuvant induces a chronic erosive polyarthritis and spondylitis in all female BALB/c mice. This occurrence is strain-specific but not haplotype-specific, and it is sex-related. The development of the arthritis is associated with the natural presence of cellular immunity to the immunizing antigen and to chondroitinase ABC-treated mouse cartilage proteoglycan. In addition, relatively more antibody to the immunizing proteoglycan is elicited in arthritic mice, and antibodies are produced that cross-react with native mouse proteoglycan. This combination of immune responses is not observed in mice that do not develop arthritis. Associated with the arthritis is the development of cytotoxicity to mouse chondrocytes and, in some animals, of rheumatoid factor, immune deposits in joint tissues and kidneys, and the production of autoantibodies to mouse type II collagen. These observations might be related to our earlier demonstration that immunity to human cartilage proteoglycan is observed in some patients with ankylosing spondylitis.
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PMID:Immunity to cartilage proteoglycans in BALB/c mice with progressive polyarthritis and ankylosing spondylitis induced by injection of human cartilage proteoglycan. 356 22

Reiter's syndrome can be induced by several different bacteria. A frequent cause in Finland is Yersinia enterocolitica serotypes 03 and 09, but these strains are rarely found in the United States. Although this does not exclude the possibility that U.S. patients with Reiter's syndrome have been infected with Yersinia, it is more likely that they develop Reiter's syndrome as a consequence of infection by non-Yersinia arthritis-causing organisms that share certain determinants with Yersinia organisms. We used radioimmunoprecipitation and sodium dodecyl sulfate-polyacrylamide gel electrophoresis to analyze the serum antibodies against iodine 125-labeled, detergent-solubilized serotype 03 Y. enterocolitica. Our results demonstrated that most serum samples of United States subjects precipitate three to five radioactively labeled Yersinia molecules. A Yersinia antigen of 88K appeared to be of possible discriminatory value. Protein A-reacting antibodies directed against this antigen were detected in only two of twenty-five patients with rheumatoid arthritis and only seven of 44 normal control subjects, compared with 18 of 27 patients with Reiter's syndrome (p less than 0.005) and eight of 16 patients with ankylosing spondylitis (p less than 0.01). Our results indicate that, despite the relatively rare occurrence of Y. enterocolitica serotypes 03 and 09 infection in the United States, examination of the immune response to the serotype 03 Yersinia strain is a promising approach to the study of Reiter's syndrome in the United States.
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PMID:Antibodies against Yersinia enterocolitica in patients with Reiter's syndrome. 387 31

Immunization of BALB/c mice with chondroitin sulfate-depleted proteoglycan (aggrecan) of fetal human cartilage produces progressive polyarthritis and ankylosing spondylitis. The development of the disease in genetically susceptible BALB/c mice is dependent upon the expression of both cell-mediated and humoral immune responses against the host mouse cartilage proteoglycan (PG). Although cartilage PGs from various species have many biochemical and immunological similarities, only a select group of PGs from fetal and newborn human, fetal pig and canine articular cartilages, human osteophytes and human chondrosarcomas are able to induce arthritis in BALB/c mice. Arthritis develops only in mice that also develop autoantibodies to self-cartilage PGs, although autoantibodies occasionally are present in non-arthritic animals as well. The protease-sensitive auto/arthritogenic epitope(s) is located in, or close to, the chondroitin sulfate (CS) attachment region of the PG molecule. The primary structure of the core protein is responsible for the autoimmune/arthritogenic effect of this select group of PGs, whereas the core protein epitopes are masked by glycosaminoglycan (GAG)-side chains. The CS side chains seem to inhibit antigen recognition in all aggrecans with arthritogenic potential, whereas a similar effect with keratan sulfate (KS) appears only in PGs of aging cartilages.
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PMID:Mapping of arthritogenic/autoimmune epitopes of cartilage aggrecans in proteoglycan-induced arthritis. 753 28

The frequency and severity of ankylosing spondylitis (AS) show a male preponderance, and androgenic steroids have been implicated in its etiology. Some reports have indicated that serum androgen levels are slightly elevated relative to estrogen levels in patients with AS as compared to controls. In more recent studies, however, serum testosterone, 17 beta-estradiol, and androstenedione levels did not significantly differ between AS patients and controls. Moreover, testosterone levels measured directly in serum can be spuriously elevated, especially in patients using phenylbutazone. Elevated serum levels of the adrenal steroids 17 alpha-hydroxyprogesterone and dehydroepiandrosterone (DHEA) sulfate have been found in patients with AS. These elevations might be explained by partial 11 beta- or 21-hydroxylase deficiencies, but may also be secondary to an enhanced stress response. In vitro studies as well as studies in animals and humans indicate that DHEA enhanced, and 17 beta-estradiol and progesterone inhibit, the cell-mediated immune response, which may play a role in the pathogenesis of AS. Oral estrogen therapy in female patients and human chorionic gonadotrophin injections in male patients with AS, increased the 17 beta-estradiol/testosterone ratio and resulted in a moderate clinical improvement. In conclusion, serum testosterone levels are not elevated in patients with AS. Therefore testosterone probably has no role in the perpetuation of long-standing AS and provides no basis for antiandrogenic treatment. Cross-sectional case-control studies, however, cannot clearly distinguish etiological factors from secondary disease effects, especially when blood sampling occurs many years after the onset of AS. Consequently, the role of sex steroids in the pathogenesis is still insufficiently elucidated.
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PMID:Androgens and ankylosing spondylitis: a role in the pathogenesis? 1041 29

To investigate the pathogenesis of abnormal ossification of the hip ligament in patients with ankylosing spondylitis (AS) by comparing gene expression profiles of the hip ligament in patients with AS to those in normal persons using DNA microarray technology, we studied 18 patients with AS (case group) who underwent total hip arthroplasty in our department from March 1, 2009 to January 31, 2010 and compared them with 6 patients with femoral neck fracture (control group) who underwent total hip replacement. We screened the first five patients in each group with the HumanWG-6 v3.0 Expression BeadChip. Compared to the control group, 519 genes in the case group showed statistically significant differences. Among these, there were 238 upregulated genes and 196 downregulated genes. Gene Ontology (GO) classification showed that differential genes in the hip joint ligaments of patients with AS were involved in immunity, cell adhesion, membrane transport, sugar metabolism, polysaccharide synthesis and metabolism, and cell motility. The Kyoto Encyclopedia of Genes and Genomes classification showed that these differential genes were involved in B cell receptor signaling pathways, adherens junction, protein export, fructose and mannose metabolism, T cell receptor signaling pathways, keratin sulfate biosynthesis, N-glycan biosynthesis, and regulation of the actin cytoskeleton. We tested 2 genes from the screened differential genes in 18 case patients and 6 control cases using real-time polymerase chain reaction. The results demonstrated that the expression of the B4GALT3 gene in the case group was 15.32 times higher than that in the control group (P < 0.01), and the expression of the RBP5 gene in the case group was 4.09 times higher than that in the control group (P < 0.01). This conformed to the microarray analysis. Our preliminary data suggest that differential gene expression in patients with AS includes the immune system, intracellular or extracellular signaling pathway, and bone matrix biosynthesis pathway, which might play important roles in hip joint ligament ossification.
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PMID:Changes in gene expression profiles of the hip joint ligament of patients with ankylosing spondylitis revealed by DNA chip. 2290 99