Soluble HLA class I antigens in serum and synovial fluid from patients with rheumatoid arthritis and other arthropathies. (1/163)

OBJECTIVES: To investigate the presence of soluble HLA class I (s-HLA) antigens in serum and synovial fluid (SF) from a large cohort of rheumatic patients. METHODS: We studied clinical and analytical data and serum samples from 300 patients [122 patients with rheumatoid arthritis (RA), 38 with osteoarthritis or osteoporosis, 29 with seronegative spondyloarthropathies, 45 patients with other rheumatic diseases] and 66 healthy controls. In addition, we studied 25 paired samples of serum and SF from these groups of subjects. In RA patients, we examined whether the levels of s-HLA in serum and SF were related to the activity of the disease. RESULTS: The mean concentrations of s-HLA molecules in serum were slightly higher in RA patients (1.2 microg/ml) than in the other four groups (1.08, 1.01, 1.09 and 0.94 microg/ml respectively). We found no correlation between serum s-HLA levels and any variable of inflammatory disease activity in RA patients. s-HLA molecules were found in SF and at levels that correlated with those found in serum (P=0.04; r=0.4). Furthermore, s-HLA levels were higher in SF from patients with RA (1.3 microg/ml) or crystal-induced arthritis (0.98 microg/ml) than in SF from those with osteoarthritis (0.38 microg/ml) (P<0.05 and P<0.005 respectively), and these levels were correlated inversely and significantly with the score on the visual analogue scale of pain (P=0.02), the number of painful joints (P=0.05) and the level of C-reactive protein (P=0.03) in RA patients. CONCLUSIONS: This is the first report to demonstrate the presence of s-HLA molecules in SF at levels that correlate with serum levels. The mean levels of s-HLA molecules were significantly higher in SF from patients with RA and crystal-induced arthritis than in SF from cases of osteoarthritis, and correlated inversely with certain variables of disease activity in RA patients.  (+info)

Prevalence of spondyloarthritis in Terceira, Azores: a population based study. (2/163)

OBJECTIVE: To determine the prevalence of spondyloarthritis (SpA) in the Caucasian population of Terceira Island, Azores. METHODS: Study subjects were recruited from people over the age of 50 years from one half of the island of Terceira (n=24 561). Seventy eight men and 78 women from each five year age group were selected, giving a total of 468 men and 468 women available for study, of whom 490 agreed to take part. These subjects were assessed by dorsal, lumbar, and pelvic radiography. Radiological sacroiliitis was identified in eight patients on whom sacroiliac computed tomography scans were performed. HLA class I typing by polymerase chain reaction with sequence-specific primers was carried out in seven cases. RESULTS: SpA was present in eight subjects (1.6%, 95% CI 0.8 to 2.7%), including seven men (2.7%) and one woman (0.4%). Three (1.2% ) male patients with definite ankylosing spondylitis were HLA-B27 positive. Only one person had a previous diagnosis of SpA. CONCLUSION: These data complement previous studies in European countries on SpA prevalence and establish an estimate of the overall prevalence of SpA in a southern European population.  (+info)

HLA-B27: natural function and pathogenic role in spondyloarthritis. (3/163)

The human leukocyte antigen HLA-B27 is strongly associated with development of a group of inflammatory arthritides collectively known as the spondyloarthritides. We have set out to define the natural immunological function of HLA-B27, and then to apply this knowledge to understand its pathogenic role. Human leukocyte antigen class 1 molecules bind antigenic peptides for cell surface presentation to cytotoxic T lymphocytes. HLA-B27 binds and presents peptides from influenza, HIV, Epstein-Barr virus, and other viruses. This leads to vigorous and specific cytotoxic T lymphocyte responses, which play an important role in the body's immune response to these viruses. HLA-B27 thus carries out its natural function highly effectively. Although many theories have been proposed to explain the role of HLA-B27 in the pathogenesis of spondyloarthropathy, we favour those postulating that the pathogenic role of HLA-B27 stems from its natural function. For example, the 'arthritogenic' peptide hypothesis suggests that disease results from the ability of HLA-B27 to bind a unique peptide or a set of antigenic peptides. Additionally, a number of lines of evidence from our laboratory and other laboratories have suggested that HLA-B27 has unusual cell biology. We have recently demonstrated that HLA-B27 is capable of forming disulfide-bonded homodimers. These homodimers are expressed on the cell surface and are ligands for a number of natural killer and related immunoreceptors, expressed on a variety of cell types including natural killer cells, T lymphocytes and B lymphocytes, and members of the monocyte/macrophage lineage. We are currently investigating the possibility that such interactions could be involved in disease pathogenesis.  (+info)

Role of NOD2 variants in spondylarthritis. (4/163)

OBJECTIVE: To investigate the role of the gene NOD2 in susceptibility to, and clinical manifestations of, ankylosing spondylitis (AS). METHODS: A case-control study of NOD2 polymorphisms known to be associated with Crohn's disease (CD) (Pro(268)Ser, Arg(702)Trp, Gly(908)Arg, and Leu(1007)fsinsC) was performed in 229 cases of primary AS with no diagnosed inflammatory bowel disease (IBD), 197 cases of AS associated with IBD (referred to as colitic spondylarthritis; comprising 78 with CD and 119 with ulcerative colitis [UC]), and 229 ethnically matched, healthy controls. Associations between NOD2 polymorphisms and several clinical features of AS, including disease severity assessed by questionnaire and age at spondylarthritis onset, were also investigated. Exclusion linkage mapping of chromosome 16 was performed in a separate group of 185 multicase families with AS. RESULTS: An association was identified between Gly(908)Arg and UC spondylarthritis (P = 0.016, odds ratio [OR] 4.6, 95% confidence interval [95% CI] 1.3-16), and a nonsignificant trend with a similar magnitude was observed in association with CD spondylarthritis (P = 0.08, OR 3.9, 95% CI 0.8-18). The Pro(268)Ser variant was inversely associated with UC spondylarthritis (P = 0.003, OR 0.55, 95% CI 0.37-0.82), but not with CD spondylarthritis. No association was demonstrated between NOD2 variants and primary AS, or between other variants of NOD2 and either UC or CD spondylarthritis. Carriage of the Pro(268)Ser polymorphism was associated with greater disease activity as measured by the Bath Ankylosing Spondylitis Disease Activity Index (P = 0.002). Although patients with CD had a younger age at spondylarthritis onset than did those with UC (22.4 years versus 26.4 years; P = 0.01), no association was noted between the NOD2 variants linked with CD and age at spondylarthritis onset. In primary AS, the presence of a gene with a magnitude of association >2.0 was excluded (exclusion logarithm of odds score less than -2.0), and no association was observed with the microsatellite D16S3136. CONCLUSION: NOD2 variants do not significantly affect the risk of developing primary AS, but may influence susceptibility to, and clinical manifestations of, colitic spondylarthritis.  (+info)

The comparison between Behcet's disease and spondyloarthritides: does Behcet's disease belong to the spondyloarthropathy complex? (5/163)

This study was to clarify whether Behcet's disease (BD) could be classified into the spondyloarthropathy (SpA) complex. It was undertaken on 58 patients with BD (BD group), 56 patients with SpA (SpA group), and 3 patients who concurrently satisfied the criteria for BD and SpA (BDSpA group). The clinical parameters and known susceptible HLA antigens were compared between BD group and SpA group. In addition, 3 patients in BDSpA group were reviewed. The prevalence of definitive sacroiliitis (SI) in BD group and SpA group was 46.4% and 5.2%, respectively. However, none had a definitive SI in healthy controls. Enthesitis was observed in 3.4% of BD group and in 50% of SpA group. The patterns of eye involvement were different between these two groups. HLA-B27 was negative in all 49 patients of BD group, whereas it was positive in 67.9% of SpA group. The prevalence of HLA-B51 was 51.7% in BD group, and that in SpA group was 21.4%. One patient in BDSpA group was considered to have concurrent BD and ankylosing spondylitis (AS). Another patient was closer to AS, and the third to BD. Conclusively, it seems that BD could not be classified into the SpA complex.  (+info)

Fast spin echo-T2-weighted sequences with fat saturation in dactylitis of spondylarthritis. No evidence of entheseal involvement of the flexor digitorum tendons. (6/163)

OBJECTIVE: To establish by means of fast spin echo (FSE)-T2-weighted sequences with fat saturation if enthesitis of the flexor digitorum superficialis and profundus tendons is the primary lesion in spondylarthritis (SpA) finger dactylitis. METHODS: Eleven dactylitic fingers and their corresponding normal, contralateral fingers, belonging to 6 patients who met the Amor criteria for SpA, were studied by FSE-T2-weighted sequences with fat saturation. RESULTS: All dactylitic fingers showed moderate or severe fluid collection in the flexor tendon synovial sheaths. Involvement of the joint cavity was simultaneously present in at least one joint in 3 (27.3%) of the 11 fingers. A mild to moderate peritendinous soft tissue edema was observed in 5 (45.5%) of the 11 affected fingers. In no dactylitic finger was bone edema observed near the insertions of the flexor digitorum superficialis or profundus tendons or in other sites of the phalanges. No lesions were observed in the 11 contralateral, clinically normal fingers. CONCLUSION: In SpA dactylitis there is no evidence of enthesitis of the flexor digitorum tendons and joint capsules.  (+info)

Cell-surface expression and immune receptor recognition of HLA-B27 homodimers. (7/163)

OBJECTIVE: HLA-B27 is capable of forming in vitro a heavy-chain homodimer structure lacking beta(2)-microglobulin. We undertook this study to ascertain if patients with spondylarthritis express beta(2)-microglobulin-free HLA-B27 heavy chains in the form of homodimers and receptors for HLA-B27 homodimers. METHODS: Expression of HLA-B27 heavy chains by mononuclear cells was analyzed by fluorescence-activated cell sorter staining, Western blotting with the monoclonal antibody HC-10, and 2-dimensional isoelectric focusing. Fluorescence-labeled tetrameric complexes of HLA-B27 heavy-chain homodimers were constructed in which each dimer comprised one His-tagged heavy chain and one biotinylated heavy chain, and were used to stain patient and control mononuclear cells and transfected cell lines. RESULTS: Patients with spondylarthritis expressed cell-surface HLA-B27 homodimers. Populations of synovial and peripheral blood monocytes, and B and T lymphocytes from patients with spondylarthritis, and controls carried receptors for HLA-B27 homodimers. Experiments with transfected cell lines demonstrated that KIR3DL1 and KIR3DL2, and immunoglobulin-like transcript 4 (ILT4), but not ILT2, are receptors for HLA-B27 homodimers. CONCLUSION: Patients with spondylarthritis express both HLA-B27 heavy-chain homodimers and receptors for HLA-B27 homodimers. This may be of significance with regard to disease pathogenesis.  (+info)

Efficacy of etanercept for treatment of Crohn's related spondyloarthritis but not colitis. (8/163)

The seronegative spondyloarthropathies (SpAs) are associated both with clinical and subclinical colitis. Recently biological blockade with the tumour necrosis factor alpha (TNFalpha) antagonists infliximab and etanercept has been shown to be effective in the treatment of SpA. However, only infliximab is efficacious in the treatment of colitis in patients with Crohn's SpA. We report on two patients with SpA and associated Crohn's disease treated with etanercept whose arthritis showed an excellent response with complete resolution of spinal pathology, whereas their Crohn's disease persisted or flared. These findings suggest that the effect of TNFalpha blockade in SpA differs between the joint and the bowel.  (+info)

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