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)

Histocompatibility typing has assumed an increasingly important role as a clinical and research tool in rheumatic diseases. The HLA antigens which are serologically defined (A and B series) are being used most extensively for clinical work, but the role of other immunologic determinants in the HLA complex is being evaluated. These include D-locus (MLC) determinants, several complement components, and immune response genes which have been well characterized in the mouse, but not in man. The products of the major histocompatibility complex are inherited in a simple Mendelian fashion as a series of co-dominant alleles. Large population studies have characterized the frequencies of various alleles, and family studies have allowed tentative mapping of the various loci within the complex on the sixth chromosome in man. A number of diseases which are considered to be autoimmune in nature are now known to be associated with specific HLA antigens. Of these disease associations, the strongest and best studied are the seronegative spondyloarthropathies which are highly associated with the B27 antigen. Included in this group are ankylosing spondylitis, Reiter's syndrome, psoriatic arthropathy, colitic arthropathy, Yersinia arthritis and a small group of juvenile rheumatoid arthritis patients with features of ankylosing spondylitis. The clinical application of tissue typing or B27 testing is most helpful in regard to difficult diagnostic problems in patients with early or atypical seronegative spondyloarthropathy. Its value as an indicator of prognosis, and its value in counselling family members is not well established. There are many interesting hypotheses regarding pathogenetic mechanisms of these rheumatic diseases based on susceptibility factors related to the major histocompatibility complex. An abnormal immune response gene within the complex is probably a key feature of the mechanism, but the exact details are little more than speculative at this point.
 ...
PMID:The histocompatibility complex and rheumatic diseases. 30 Aug 26

The close relationship between ankylosing spondylitis and the presence of the transplantation antigen HL-A 27 is well recognized. An attractive explanation for this has been that the gene coding for this antigen exists in marked linkage disequilibrium with an abnormal immune response gene. We have suggested, in contrast, that HL-A 27 may have a more direct importance because of a defective epistatic interaction between the gene coding for this antigen and a distinct disease susceptibility gene for AS, which may therefore be situated some distance from the major histocompatibility complex.
 ...
PMID:Prevalence of ankylosing spondylitis and its association with HL-A 27. 120 67

The association between three major spondyloarthritic diseases, ankylosing spondylitis, Reiter's syndrome, and reactive arthritis, and the major histocompatibility complex (MHC) class 1 antigen HLA-B27 is well documented. The hypothesis of cross-reactivity between HLA-B27 and the antecedent infection-causing Gram-negative pathogens such as Salmonella, Shigella and Yersinia has been suggested by in vitro studies employing monoclonal antibodies. We have examined the possibility of such cross-reactivity in vivo using various rabbit immune sera and patient sera as the source of cross-reacting antibody. Mouse L cells were transfected with HLA-A3 or HLA-B27 and used as a source of antigen. Western blot analysis employing denatured antigen, FACS analysis employing native antigen and immunoprecipitation studies were undertaken to detect cross-reacting antibodies generated in vivo to HLA-B27 antigen. Antibodies generated in vivo by infection in patients or immunization in animals against arthritogenic bacteria did not demonstrate any cross-reactivity with HLA-B27 by any of the methods used. As defined by the humoral immune response, molecular mimicry appears unlikely to explain the role of B27 in the pathogenesis of reactive arthritis.
 ...
PMID:HLA-B27/microbial mimicry: an in vivo analysis. 147 90

Antigen processing for presentation of peptide epitopes by major histocompatibility complex (MHC) class I molecules involves genes in the MHC class II region. Among these, PSF1 and PSF2 encode subunits of a transporter, which presumably delivers cytosolic peptides across the endoplasmic reticulum membrane to class I molecules. This close functional relationship of the transporter and class I heavy chain genes and their linkage within the MHC raise the question of whether PSF1 and PSF2, like most class I genes, are polymorphic. By single-strand conformation polymorphism analysis and DNA sequencing, a small number of amino acid sequence variants of both PSF1 and PSF2 was identified in a panel of cell lines. This limited polymorphism may contribute to a higher degree of variability at the level of the functional transporter, in which different alleles of the PSF1 and PSF2 subunits may be combined. A possible involvement of the PSF1 and PSF2 genes in susceptibility to MHC-associated diseases was examined in a preliminary assessment in patients with ankylosing spondylitis, insulin-dependent diabetes mellitus, or celiac disease.
 ...
PMID:Allelic variants of the human putative peptide transporter involved in antigen processing. 157 Mar 16

Although ankylosing spondylitis (AS) is known to be strongly associated with the class I major histocompatibility complex antigen HLA-B27, B27 is probably not the only genetic factor involved in the pathogenesis of AS. Because of the involvement of tumor necrosis factor (TNF) in cartilage damage and the localization of the TNF genes in the proximity of the HLA-B locus, we investigated the association between AS and TNF alleles. The frequencies of the restriction fragment length polymorphisms linked to the TNF genes were determined in 73 AS patients and 81 controls. No differences were observed between AS patients and controls with respect to the frequencies of the TNF restriction fragment length polymorphisms.
 ...
PMID:Restriction fragment length polymorphism of the tumor necrosis factor region in patients with ankylosing spondylitis. 167 16

CD2R is an activation-associated epitope unmasked by a conformational change of the CD2 cell-surface glycoprotein. In spite of elaborate studies on the role of CD2 and CD2R in adhesion and stimulation of T cells in vitro, no instances of CD2R expression in vivo were known to date. We report high levels of CD2R observed on blood and synovial fluid T cells in rheumatoid arthritis and on peripheral blood T cells in juvenile rheumatoid arthritis, systemic lupus erythematosus, ankylosing spondylitis, and Lyme disease. In vivo, expression of CD2R was restricted to T cells, not limited to a particular T-cell subset and not correlated with the expression of p55 interleukin 2R (IL-2R) (CD25) or major histocompatibility complex (MHC) class II molecules. When stimulated to proliferation via CD2 or CD3, ex vivo CD2R+ T cells showed the same basic activation requirements as CD2R-T cells.
 ...
PMID:Expression of the CD2 activation epitope T11-3 (CD2R) on T cells in rheumatoid arthritis, juvenile rheumatoid arthritis, systemic lupus erythematosus, ankylosing spondylitis, and Lyme disease: phenotypic and functional analysis. 171 5

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.
 ...
PMID:Role of enterobacteria and HLA-B27 in spondyloarthropathies: studies with transgenic mice. 211 64

Considerable evidence indicates that genes residing within the major histocompatibility complex (MHC) influence susceptibility to certain rheumatic diseases, such as ankylosing spondylitis (AS) and rheumatoid arthritis (RA). However, it has not yet been possible to precisely identify the gene(s) responsible for conferring enhanced susceptibility to these diseases. The availability of recombinant DNA technology should accelerate progress in obtaining this goal. A particularly promising method in this regard is restriction fragment length polymorphism (RFLP) analysis using appropriate class I and class II MHC gene probes. In preliminary studies, RFLPs have been identified for AS and RA which associate with susceptibility to the disease. Further studies using this approach should permit localization and precise identification of the disease susceptibility gene(s) for these diseases.
 ...
PMID:Analysis of restriction fragment length polymorphisms in rheumatic diseases. 289 32

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.
 ...
PMID:Restriction fragment length polymorphism analysis in ankylosing spondylitis. 290 63

A 435-kilobase (kb) DNA segment, which is centromeric to HLA-B in the human major histocompatibility complex, was isolated by chromosome walking with overlapping cosmids. Within the cloned region, the genes for the tumor necrosis factors (TNFs) alpha and beta and HLA-B were 210 kb apart. The human homolog of a mouse gene, B144, was located next to TNF alpha. Moreover, the presence of additional genes was suggested by a large cluster of CpG islands. With cosmid probes, several distinct transcripts were detected in RNA samples from a variety of cell lines. Altogether, five novel genes were identified by isolation of corresponding complementary DNA clones. These "HLA-B-associated transcripts" (BATs) were mapped to different locations within a 160-kb region that includes the genes for TNF alpha and TNF beta. The presence of the genes for BAT1 and BAT5 in the vicinity of HLA-B again raises the question of which gene in this region determines susceptibility to ankylosing spondylitis.
 ...
PMID:A new cluster of genes within the human major histocompatibility complex. 291 34


1 2 3 4 5 6 7 8 Next >>