Nuclear factor-kappa B activity in T cells from patients with rheumatic diseases: a preliminary report. (1/182)

OBJECTIVE: The NF-kappa B/Rel family of transcription factors regulates the expression of many genes involved in the immune or inflammatory response at the transcriptional level. The aim of this study was to determine whether distinctive patterns of NF-kappa B activation are seen in different forms of joint disease. METHODS: The DNA binding activity of these nucleoproteins was examined in purified synovial and peripheral T cells from patients with various chronic rheumatic diseases (12: four with rheumatoid arthritis; five with spondyloarthropathies; and three with osteoarthritis). RESULTS: Electrophoretic mobility shift assays disclosed two specific complexes bound to a NF-kappa B specific 32P-labelled oligonucleotide in nucleoproteins extracted from purified T cells isolated from synovial fluid and peripheral blood of patients with rheumatoid arthritis. The complexes consisted of p50/p50 homodimers and p50/p65 heterodimers. Increased NF-kappa B binding to DNA in synovial T cells was observed relative to peripheral T cells. In non-rheumatoid arthritis, binding of NF-kappa B in synovial T cells was exclusively mediated by p50/p50 homodimers. CONCLUSION: Overall, the results suggest that NF-kappa B may play a central part in the activation of infiltrating T cells in chronic rheumatoid arthritis. The activation of this nuclear factor is qualitatively different in rheumatoid synovial T cells to that in other forms of non-rheumatoid arthritis (for example, osteoarthritis, spondyloarthropathies).  (+info)

Fungal spinal osteomyelitis in the immunocompromised patient: MR findings in three cases. (2/182)

The MR imaging findings of fungal spinal osteomyelitis in three recipients of organ transplants showed hypointensity of the vertebral bodies on T1-weighted sequences in all cases. Signal changes and enhancement extended into the posterior elements in two cases. Multiple-level disease was present in two cases (with a total of five intervertebral disks involved in three cases). All cases lacked hyperintensity within the disks on T2-weighted images. In addition, the intranuclear cleft was preserved in four of five affected disks at initial MR imaging. MR features in Candida and Aspergillus spondylitis that are distinct from pyogenic osteomyelitis include absence of disk hyperintensity and preservation of the intranuclear cleft on T2-weighted images. Prompt recognition of these findings may avoid delay in establishing a diagnosis and instituting treatment of opportunistic osteomyelitis in the immunocompromised patient.  (+info)

Rheumatic disease and the Australian aborigine. (3/182)

OBJECTIVE: To document the frequency and disease phenotype of various rheumatic diseases in the Australian Aborigine. METHODS: A comprehensive review was performed of the archaeological, ethnohistorical, and contemporary literature relating to rheumatic diseases in these indigenous people. RESULTS: No evidence was found to suggest that rheumatoid arthritis (RA), ankylosing spondylitis (AS), or gout occurred in Aborigines before or during the early stages of white settlement of Australia. Part of the explanation for the absence of these disorders in this indigenous group may relate to the scarcity of predisposing genetic elements, for example, shared rheumatoid epitope for RA, B27 antigen for AS. In contrast, osteoarthritis appeared to be common particularly involving the temporomandibular joint, right elbow and knees and, most probably, was related to excessive joint loading in their hunter gatherer lifestyle. Since white settlement, high frequency rates for rheumatic fever, systemic lupus erythematosus, and pyogenic arthritis have been observed and there are now scanty reports of the emergence of RA and gout in these original Australians. CONCLUSION: The occurrence and phenotype of various rheumatic disorders in Australian Aborigines is distinctive but with recent changes in diet, lifestyle, and continuing genetic admixture may be undergoing change. An examination of rheumatic diseases in Australian Aborigines and its changing phenotype may lead to a greater understanding of the aetiopathogenesis of these disorders.  (+info)

Studying patients with inflammatory back pain and arthritis of the lower limbs clinically and by magnetic resonance imaging: many, but not all patients with sacroiliitis have spondyloarthropathy. (4/182)

OBJECTIVE: Clinical and magnetic resonance imaging (MRI) data of 170 consecutive patients with inflammatory back pain (IBP) and/or oligoarthritis of the lower limbs were evaluated in a retrospective study. The aim was to determine the frequency of sacroiliitis and spondyloarthropathy (SpA) in this population, and to assess the significance of HLA B27 measurements for diagnosis in early disease. METHODS: Pelvic X-rays were performed in all IBP patients and dynamic MRI of the sacroiliac joints in patients with IBP who had indefinite results on sacroiliac X-rays (n = 32). RESULTS: European Spondyloarthropathy Study Group criteria for SpA were fulfilled by 106/170 patients (62.4%); eight additional patients had symptoms suggestive of SpA (4.7%). The most frequent SpA subset was undifferentiated SpA (uSpA), diagnosed in 46/106 patients (43.4%). Sacroiliitis was detected by MRI in 21/32 patients with IBP and unclear X-rays (65.6%). Of those, 14 were diagnosed as SpA and seven females with moderate unilateral sacroiliitis, but no features of SpA, also not on follow-up (at least 1 yr), were classified as undifferentiated sacroiliitis (US). Ten of the 14 SpA (71.4%) and none of the seven US patients were HLA B27 positive. CONCLUSION: HLA B27 positivity in IBP patients with MRI-proven sacroiliitis positively predicts SpA. uSpA is a frequent SpA subset. There are HLA B27-negative non-SpA patients with moderate unilateral sacroiliitis whom we propose to be classified as US.  (+info)

Increased Ed-B fibronectin plasma levels in spondyloarthropathies: comparison with rheumatoid arthritis patients and a healthy population. (5/182)

OBJECTIVE: To determine, for the first time, plasma levels of general fibronectin (Fn) and two spliced isoforms, Ed-A and Ed-B, in patients with spondyloarthropathy (SpA) in comparison with rheumatoid arthritis (RA) patients and healthy volunteers (HV). METHODS: Plasmas (EDTA) as well as clinical data, erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) levels were collected in two groups of 10 patients fulfilling the European Spondylarthropathy Study Group criteria for SpA or the 1987 American College of Rheumatology criteria for RA. Plasmas of 21 blood donors served as controls. Plasma levels of Fns were determined by using an in-house immunocapture ELISA, using monoclonal antibodies (MAbs) against general Fn and its isoforms. RESULTS: Total Fn plasma levels were significantly higher in the SpA group (mean+/-S.D.=1387+/-569 mg/l) than in the RA group (684+/-196 mg/l; P=0.02) and in HV (303+/-211 mg/l; P<0.0001). Ed-A Fn levels appeared higher in SpA (23+/-10.4 mg/l) and RA (32.5+/-16.5 mg/l) groups than in the HV group (2.8+/-0.9 mg/l; P=0.0003 and P<0.0001, respectively), without a significant difference between SpA and RA groups. Ed-B Fn levels were higher in SpA (6.9+/-2.1 mg/l) than in RA (3.2+/-1.9 mg/l; P=0. 02) and HV (1.1+/-0.8 mg/l; P=0.0003) groups. No significant correlation was observed in SpA patients between each Fn level and clinical activity, ESR or CRP levels. CONCLUSIONS: This study showed an increase in plasma levels of Fn and Ed-B Fn in SpA patients compared with RA patients and HV, which could not be attributed solely to systemic inflammation. It may be hypothesized that Ed-A and Ed-B Fn might reflect local turnover in inflamed tissues, and that Ed-B Fn might be particularly involved in the musculoskeletal inflammatory process of SpA.  (+info)

Brucellar spondylitis: review of 35 cases and literature survey. (6/182)

Thirty-five patients aged 14-74 years (average, 54 years) who had brucellar spondylitis were treated between January 1991 and December 1997. The time from onset of symptoms to diagnosis of spondylitis ranged from 1 week to 8 months (median, 9 weeks). Back or neck pain (100% of patients), fever (66%), and constitutional symptoms (57%) were the most common symptoms. Cultures of blood specimens from 26 patients (74%) were positive for Brucella melitensis. The duration of antimicrobial therapy (median, 120 days; range, 45-535 days) varied according to clinical response and the presence of epidural and paravertebral masses. One of the 35 patients underwent surgical treatment of a spinal epidural abscess. Therapy failed for 9 patients (26%; 95% confidence interval [CI], 12%-43%), and 5 (14%; 95% CI, 5%-30%) had a relapse. There were no deaths or severe sequelae in this study. Brucellar spondylitis causes considerable suffering and absenteeism from work, but long-term clinical responses are favorable.  (+info)

Misfolding of HLA-B27 as a result of its B pocket suggests a novel mechanism for its role in susceptibility to spondyloarthropathies. (7/182)

The MHC class I protein HLA-B27 is strongly associated with susceptibility to spondyloarthropathies and can cause arthritis when expressed in rats and mice, implying a direct role in disease pathogenesis. A prominent hypothesis to explain this role suggests that the unique peptide binding specificity of HLA-B27 confers an ability to present arthritogenic peptides. The B pocket, a region of the peptide binding groove that is an important determinant of allele-specific peptide binding, is thought to be critical for arthritogenicity. However, this hypothesis remains unproven. We show that in addition to its role in peptide selection, the B pocket causes a portion of the pool of assembling HLA-B27 heavy chains in the endoplasmic reticulum to misfold, resulting in their degradation in the cytosol. The misfolding phenotype is corrected by replacing the HLA-B27 B pocket with one from HLA-A2. Our results suggest an alternative to the arthritogenic peptide hypothesis. Misfolding and its consequences, rather than allele-specific peptide presentation, may underlie the strong link between the HLA-B27 B pocket and susceptibility to spondyloarthropathies.  (+info)

Evolution of chronic recurrent multifocal osteitis toward spondylarthropathy over the long term. (8/182)

OBJECTIVE: To retrospectively assess, with a sufficiently long followup (mean 11.6 years; median 9 years), the long-term outcome of chronic recurrent multifocal osteitis (CRMO), a multifocal, inflammatory bone disease. METHODS: Patients included were 8 children/adolescents and 7 adults with no family history of rheumatic disease who had been diagnosed as having CRMO between 1979 and 1995. Ten patients had undergone at least 1 bone biopsy of the lesions, with histologic examination and multiple cultures. In 1996, in addition to an in-depth interview, 12 patients underwent an extensive physical examination, laboratory evaluation, HLA-A, B, C, and DR typing, bone radiography and scintigraphy, and computed tomography scan of the sternoclavicular and sacroiliac joints. RESULTS: Remission was observed in 3 patients. The other 12 patients developed various associations of vertebral (n = 10), sacroiliac (n = 6), anterior thoracic (n = 7), peripheral articular (n = 2), enthesopathic (n = 4), or dermatologic (palmoplantar pustulosis in 3 cases and psoriasis in 2) involvements. Spine involvement was the most common and occurred the earliest (median time to appearance after the onset of osteitis 5.63 years). Clinical sacroiliitis was always unilateral. No patients carried the HLA-B27 haplotype. CRMO responded well to nonsteroidal antiinflammatory drugs. Twelve patients met the European Spondylarthropathy Study Group criteria for spondylarthopathy. CONCLUSION: After 10 years, CRMO had usually evolved to spondylarthropathy, but with certain features not usually seen in the latter: predominantly, unilateral sacroiliitis, no familial form, and no link with HLA-B27.  (+info)