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

Ankylosing spondylitis and Reiter's syndrome are the two major spondyloarthropathies highly associated with human leukocyte antigen (HLA) B27. Although the development of spondylitis is unclear, it has been hypothesized that HLA-B27 may predispose to spondyloarthropathies via the phenomenon of molecular mimicry. A computer search for homologies between HLA-B27 and microbes revealed a sequence of six consecutive amino acids (glutamine-threonine-aspartic acid-arginine-glutamic acid-aspartic acid) shared by HLA-B27.1 (residues 72 to 77), and Klebsiella pneumoniae nitrogenase (residues 188 to 193). Antibodies raised against a peptide derived from HLA-B27 containing this six-amino-acid sequence cross-reacted with the peptide derived from Klebsiella that contained these six amino acids, and vice-versa. These antibodies also reacted with articular tissues from HLA-B27-positive patients with ankylosing spondylitis. Sera from 53 percent of Reiter's patients and 27 percent of patients with ankylosing spondylitis showed binding to these same peptides. These results suggest that molecular mimicry may have a role in disease development.
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PMID:Molecular mimicry between human leukocyte antigen B27 and Klebsiella. Consequences for spondyloarthropathies. 246 50

The importance of the association between the human histocompatibility antigen human leukocyte antigen-B27 and ankylosing spondylitis is undisputed, but its biologic significance remains unresolved. We have demonstrated specific cross reactivity between a range of enteric bacteria and a specific determinant found only on the surfaces of cells from human leukocyte antigen-B27-positive persons with ankylosing spondylitis. We have proposed that the genetic element coding for this cross-reactive determinant is mobile and that its acquisition by B27-positive cells in vivo represents an important step in the eventual development of ankylosing spondylitis.
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PMID:Cross-reacting bacterial determinants in ankylosing spondylitis. 246 51

We utilized the technique of restriction fragment length polymorphism (RFLP) analysis in order to examine class I major histocompatibility complex genes in 52 Alabama ankylosing spondylitis patients and 107 local control subjects. A 9.2-kilobase PvuII RFLP was identified using the class I-specific B7 cDNA probe pDP001 that was closely associated with ankylosing spondylitis, most specifically with peripheral joint (including shoulder and hip) involvement. This fragment is associated with human leukocyte antigen A3 and A9 alleles, and segregation analysis in 11 multiplex families showed the RFLP to frequently segregate independently of B27 haplotypes. Two more recent studies have not confirmed the association of the 9.2-kilobase PvuII RFLP with ankylosing spondylitis per se, believed to be due to clinical and possibly genetic differences between the patient groups studied. These data strongly suggest at least one other major histocompatibility complex class I gene to be operative in predisposition to or modification of ankylosing spondylitis.
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PMID:Restriction fragment length polymorphism analysis in ankylosing spondylitis. 290 63

The major histocompatibility complex on the sixth chromosome controls expression of a complex series of cell surface antigens which comprise the human leukocyte antigen (HLA) system. These markers, beyond their importance in human organ transplantation, have been demonstrated to occur with an increased prevalence in certain disease states. The group of conditions showing the closest association with specific HLA antigens are the "spondyloarthropathies." These include ankylosing spondylitis (AS), Reiter's syndrome (RS), psoriatic arthritis (PsA), and the arthritis of inflammatory bowel disease (AIBD). Clinical and radiographic studies were made of 310 unrelated caucasoid patients with seronegative arthritis. HLA-A, B, C, and DR typing were performed using the microdroplet lymphocyte cytotoxicity test. Statistically increased prevalences of A26, B27, and Bw38 were observed, while B27 was associated with spinal involvement regardless of diagnosis (90 percent in AS p less than 0.0001). Experiments found A26 (23 percent p less than 0.001) and Bw38 (38 percent p less than 0.0001) in patients with PsA. Spondyloarthritis patients with spinal involvement who lacked B27 frequently had B7. The HLA DR typing for seven specificities was carried out in 196 patients. It was found that DRw4 (52 percent p less than 0.03) and DRw7 (39 percent p less than 0.04) were increased in the PsA patients. This study further confirms the close association of HLA antigens and the spondylarthropathies.
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PMID:The major histocompatibility complex. 695 Jun 86

The genes of the human leukocyte antigen (HLA) region, the major histocompatibility complex (MHC) of humans, control a variety of functions involved in immune response and influence susceptibility to over 40 diseases. Theoretical studies in the development of models to determine the modes of inheritance of the HLA-associated diseases have led to a better understanding of the inheritance patterns in insulin-dependent diabetes mellitus (IDDM), rheumatoid arthritis, multiple sclerosis, ankylosing spondylitis, hemochromatosis, celiac disease, and others. It is now clear that many of the HLA-associated diseases involve heterogeneity in their HLA components, as well as non-HLA genetic factors. This review is presented using HLA-associated diseases, and in particular IDDM, as the example of interest, but the observations and techniques presented have direct relevance to the study of all human diseases with a complex genetic component. Three methods for localizing disease-predisposing genes are presented: (1) association studies, including population, family, and relative predispositional effects, (2) affected sib pair and other affected-relative methods, and (3) lod score analysis. A variety of complementary methods for studying the mode(s) of inheritance of the alleles at the disease-predisposing locus and for identifying the alleles and amino acids directly involved in the disease process also are presented.
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PMID:HLA disease associations: models for the study of complex human genetic disorders. 759 90

Acute anterior uveitis (AAU) or iritis is an inflammatory disorder of the anterior structures of the eye that may be associated with a number of disease entities. A significant proportion of patients will have no evidence of an underlying disorder and are labeled as idiopathic. Within this group approximately 50% will possess the human leukocyte antigen, HLA-B27, and some will have an associated spondyloarthropathy such as ankylosing spondylitis or Reiter's syndrome. Nevertheless, a number of HLA-B27-positive patients have no apparent underlying rheumatic disorder. The potential interplay of HLA-B27 and certain infective agents in the pathogenesis of AAU is discussed with particular reference to Yersinia species. Presentation of a uveitogenic peptide, similar to the arthritogenic peptide model in spondyloarthropathies, may be a mechanism involved in the development of AAU. Experimental models in animals have increased our understanding of the roles of retinal proteins and bacterial peptides, as well as T cells and cytokines, in the pathogenesis of uveitis. As in animal models of arthritis, certain retinal peptides (in conjunction with adjuvant therapy) can induce uveitis in animals. The treatment of isolated AAU usually involves topical medication and the prognosis is good. Occasional cases, especially those associated with systemic disorders, may require the addition of systemic corticosteroids or other immunosuppressive medications.
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PMID:Acute anterior uveitis: clinical and experimental aspects. 766 47

Although human leukocyte antigen (HLA) B27 has been directly implicated in the pathogenesis of ankylosing spondylitis (AS), additional evidence favours the involvement of an additional genetic factor(s). In a previous population analysis of AS patients selected for a history of acute anterior uveitis (AAU), we had demonstrated a phenotypic association between polymorphism in an HLA-linked proteasome subunit gene, LMP2, and the development of AAU and peripheral arthritis. In the present study, we have assessed the relative risk of homozygosity for the LMP2 arginine variant, the disease-associated genotype, for these complications in an unselected group of 86 patients with AS seen sequentially in 1 centre by 1 rheumatologist over a 2-y period. LMP2 genotyping was performed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) using the CfoI restriction enzyme. Homozygosity for the LMP2 arginine variants was observed in 68.4% of AS patients who had had AAU as compared to 41.7% without AAU (relative risk 3.0; chi 2 = 6.1, p < 0.02). The proportion of AS patients with peripheral arthritis homozygous for the arginine residue was 55.2% as compared to 52.6% without this complication (relative risk 1.1; p > 0.05). Our data suggest a primary association with the development of AAU and provide evidence for genetic heterogeneity in distinct clinical subgroups of patients with AS as a basis for phenotypic variation.
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PMID:Polymorphism in the LMP2 gene influences the relative risk for acute anterior uveitis in unselected patients with ankylosing spondylitis. 776 65

A rare case of ankylosing spondylitis with interstitial pulmonary disease of the upper lung field, at an early stage in the disease, is described. The patient, a 35-year-old asymptomatic woman, was admitted to the hospital due to an abnormal chest radiograph that was found during preoperative evaluation for a toxic adenoma of the thyroid gland. Her mother and sister were also found to suffer from ankylosing spondylitis but without lung involvement. History, physical and laboratory examination as well as open lung biopsy excluded other causes of an interstitial pulmonary disease. The diagnosis of ankylosing spondylitis was based on clinical, radiographic, positive human leukocyte antigen (HLA-B27) and histologic findings.
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PMID:Diffuse interstitial lung disease as an early manifestation of ankylosing spondylitis. 856 97

We investigated the relationship between anterior uveitis with ankylosing spondylitis (AS) and human leukocyte antigen (HLA) alleles. Forty patients were studied, 19 with anterior uveitis and 21 without it. No deviation in the frequencies of HLA-B27 antigen and related alleles were observed between the two groups of patients. Twelve cases (63.2%) with anterior uveitis had expressed HLA-DR8 (DRB1 0803). On the other hand, only 1 case had expressed the same antigen and this difference was statistically significant (relative risk: 34.3 Pc < 0.007) as we reported previously. We found HLA-DR8 was a candidate for susceptibility to anterior uveitis in AS.
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PMID:[Anterior uveitis with ankylosing spondylitis and HLA]. 864 41

Fibrodysplasia ossificans progressiva is a rare heritable disorder of connective tissue characterized by skeletal malformations and by progressive heterotopic ossification. It has been suggested that the genetic marker human leukocyte antigen B27 may be associated with fibrodysplasia ossificans progressiva, as it is with ankylosing spondylitis, another disorder with less severe hyperostosis. Genomic deoxyribonucleic acid from 23 classically affected patients with fibrodysplasia ossificans progressiva was screened for the human leukocyte antigen B27 allele by polymerase chain reaction. Only two of the 23 patients (9%) with fibrodysplasia ossificans progressiva who were examined showed the presence of the human leukocyte antigen B27 allele, an incidence that corresponds to the 8% frequency of individuals within the general population not affected with ankylosing spondylitis. These data suggest that the human leukocyte antigen B27 allele does not occur more commonly in the genotype of patients with fibrodysplasia ossificans progressiva than in the general population, and that the pathogenesis of heterotopic bone in fibrodysplasia ossificans progressiva differs from that of ankylosing spondylitis and other human leukocyte antigen B27 positive disorders.
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PMID:Human leukocyte antigen B27 allele is not correlated with fibrodysplasia ossificans progressiva. 957 12


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