Histocompatibility antigens in inflammatory bowel disease. Their clinical significance and their association with arthropathy with special reference to HLA-B27 (W27).
Histocompatibility (HLA) antigen phenotypes have been studied in 100 patients with ulcerative colitis, 100 with Crohn's disease, and 283 normal controls. In addition the incidence of ankylosing spondylitis, sacroiliitis, and "enteropathic" peripheral arthropathy was determined in the patients with inflammatory bowel disease (IBD). There was no significant difference in antigen frequency between patients and controls. However, the incidence of HLA-B27 was increased in the patients complicated by ankylosing spondylitis and/or sacroiliitis in both ulcerative colitis and Crohn's disease. In contrast, none of the 29 IBD patients with "enteropathic" peripheral arthropathy had B27 antigen. Furthermore, ankylosing spondylitis was found more frequently in ulcerative colitis bearing HLA-B27 compared with non-B27 patients (P less than 0-01). The same was found in Crohn's disease, although this difference was not statistically significant. In addition, 12 of 14 ulcerative colitis patients and five out of six Crohn's patients with HLA-B27 had total colitis, compared with the frequency of total colitis in non-B27 patients (P less than 0-024 and less than 0-03 respectively). The data suggest that B27 histocompatibility antigen could be a pathogenetic discriminator between the arthropathies in IBD and may be of prognostic significance with respect to extension and severity of the disease. (+info)
Cauda equina syndrome in ankylosing spondylitis: a report of six cases.
Six patients with ankylosing spondylitis and features of a cauda equina syndrome are described. The myelographic findings are discussed in relation to the pathogenesis of the disorder and its natural history. Present experience suggests that the cauda equina syndrome is a more common complication of ankylosing spondylitis than is usually thought. (+info)
Cervical spondylotic myelopathy in elderly people: a high incidence of conduction block at C3-4 or C4-5.
OBJECTIVES: To precisely localise the site of conduction block in elderly patients with cervical spondylotic myelopathy in the presence of multilevel compression shown by MRI. METHODS: A total of 44 patients aged 65 and older underwent serial intervertebral recording of spinal somatosensory evoked potentials (SSEPs) from either the intervertebral disc or the ligamentum flavum after epidural stimulation. The site of conduction block identified by abrupt reduction in size of the negative peak was designated as the 0 level with the other levels numbered in order of distance assigning a minus sign caudally. RESULTS: A single site of focal conduction block was disclosed in 42 patients, 23 (55%) at C3-4, 17 (40%) at C4-5, and two (5%) at C5-6. At these levels (0), the amplitude of the negative component was reduced (p<0.0001) to 29% and the area to 22%, with a concomitant increase (p<0.0001) of the initial positive component to 150% in amplitude and 293% in area as compared to the-2 level which was taken as the baseline (100%). CONCLUSIONS: A high incidence (95%) of focal conduction block at C3-4 or C4-5 with normal conduction at C5-6 and C6-7 characterises cervical spondylotic myelopathy in elderly people. Incremental SSEP studies documenting the site of conduction block will help exclude clinically silent cord compression, directing the surgical intervention to the appropriate level of concern. (+info)
Immune function in ankylosing spondylitics and their relatives: influence of disease and HLA B27.
So as to distinguish the separate influences of ankylosing spondylitis (AS) and possible HLA B27 associated immune response genes on immune response patterns, a battery of immunological tests were performed on fourteen patients with AS and their first-degree relatives. Previously unrecognized AS was detected by clinical and radiological means. Individuals with ankylosing spondylitis had significantly higher serum IgG and IgA concentrations than both their B27 positive and B27 negative relatives. B27 positive relatives had significantly lower phytohaemagglutinin (PHA) lymphocyte transformations than B27 negative relatives (P less than 0.01), while there was no difference between the ankylosing spondylitic and B27 positive groups. Antibody titres to Streptokinase/Streptodornase were significantly higher in the B27 positive individuals, with or without AS, than their B27 negative relatives (P less than 0.005 and P less than 0.02 respectively). These results show that serum immunoglobulin differences were associated with disease, while differences in PHA stimulation and varidase antibody titres were associated with the B27 antigen. These findings may indicate the presence of HLA associated immune response genes including those involved with reactions to a particular antigenic component of Streptokinase/Streptodornase. (+info)
Predominance of mononuclear cells expressing the chemokine receptor CCR5 in synovial effusions of patients with different forms of arthritis.
OBJECTIVE: To study the role of the chemokine receptors CCR5 and CCR2 in patients with arthritis. METHODS: CCR5 expression on peripheral blood leukocytes was compared with the expression on leukocytes isolated from the synovial fluid of 20 patients with different rheumatic joint diseases. Three additional samples were studied for CCR2 expression. The expression of chemokine receptors on blood and synovial fluid leukocytes was determined by 3-color flow cytometry analysis. To test CCR5 receptor down-modulation from the cell surface, leukocytes were incubated in vitro with a RANTES (regulated on activation, normal T cell expressed and secreted) derivative, aminooxypentane (AOP)-RANTES. Patients were genotyped for the delta32 CCR5 deletion by polymerase chain reaction. RESULTS: A high percentage of CCR5-expressing CD4+ and CD8+ T cells (74% and 81%, respectively), monocytes (51%), and natural killer cells (35%) was found in the synovial fluid of all patients, whereas in the peripheral blood, only a small percentage of these cells expressed CCR5 (13%, 32%, 7.8%, and 4%, respectively). Infiltration of CCR5-positive leukocytes was not reduced in CCR5-heterozygous patients. A similar, but less pronounced, distribution was observed for CCR2-positive T cells. In vitro, CCR5 was completely down-modulated on synovial fluid leukocytes by AOP-RANTES. CONCLUSION: The predominance of CCR5-positive mononuclear cells in the synovial effusions of patients with arthritis suggests an important role for CCR5 in the process of joint inflammation, and identifies CCR5 as a possible new target for therapeutic intervention. (+info)
Ankylosing spondylitis: what is the optimum duration of a clinical study? A one year versus a 6 weeks non-steroidal anti-inflammatory drug trial.
OBJECTIVE: To consider the relevance of the duration of a clinical trial in ankylosing spondylitis: long-term (i.e. 1 yr) vs short-term (i.e. 6 weeks) assessment of a non-steroidal anti-inflammatory drug (NSAID)-placebo controlled study. METHODS: The design was a prospective, multicentre, double-blind, placebo-controlled study of 6 weeks duration with a 12 months double-blind extension. Study drugs were placebo (n = 121) or active NSAID (n = 352). A decrease of at least 50% in pain and/or global assessment and/or functional impairment during the study defined the response to treatment. The percentage of patients discontinuing the study drug over time (life table analysis) permitted the evaluation of both the efficacy and toxicity. RESULTS: Among the 473 recruited patients, the percentage of responders was similar at 1 yr and week 6 with a highly statistically significant difference in favour of the active NSAID groups when compared to placebo (at 1 yr, 17% in the placebo group vs 37, 50 and 43% in the piroxicam 20 mg, meloxicam 15 mg and meloxicam 22.5 mg, respectively, for the patient's overall assessment) without any statistically significant difference between the three active groups. However, evaluation of the patients discontinuing the study drug during the 1 yr of the study permitted the detection of a statistically significant difference between the active NSAID groups. A lower percentage of patients taking meloxicam 22.5 mg had to discontinue the study drug when compared to either meloxicam 15 mg or piroxicam 20 mg (37% vs 53% and 53%, respectively, P < 0.05). By 52 weeks, drug-related upper gastrointestinal adverse events occurred in 13, 32, 20 and 18% in the placebo, piroxicam 20 mg, meloxicam 15 mg and meloxicam 22.5 mg groups, respectively. Some of the adverse events occurred only after week 6. CONCLUSION: This study suggests that a 1 yr trial might be of optimum value compared to a 6 week assessment in order to define better the efficacy and tolerability of NSAIDs in ankylosing spondylitis. (+info)
Relationship between urinary pyridinium cross-links, disease activity and disease subsets of ankylosing spondylitis.
OBJECTIVE: In this study, we aimed to determine the urinary levels of pyridinium cross-links and urinary beta-isomerized fragments derived from the C-telopeptide of the alpha1 chain of type I collagen (beta-CTX) as markers of bone resorption in patients with ankylosing spondylitis (AS), and to study their relationship to markers of disease activity [erythrocyte sedimentation rate (ESR)] and to disease subsets of this condition. METHODS: The serum calcium, osteocalcin (OC), parathormone (PTH), 25 OHD3 levels, beta-CTX and the urinary combined free pyridinolines (f-Pyr + f-Dpyr), urinary free deoxypyridinoline (f-Dpyr) and urinary free pyridinoline (f-Pyr) were evaluated and compared in 32 AS patients and 25 controls. Bone mineral density (BMD) was evaluated at the lumbar spine and the femoral neck. RESULTS: The serum markers of bone metabolism (serum calcium, PTH, 25 OHD3 and OC) were in the normal range in the AS group. AS patients had a lowered lumbar spine BMD (P = 0.01) (corresponding T score: P = 0.03), but femoral neck BMD did not differ significantly between AS and controls (P = 0.08) (corresponding T score: P = 0.11). There was no difference in the urinary levels of pyridinium cross-links and beta-CTX between AS patients and controls. A positive correlation between ESR, (f-Pyr + f-Dpyr) (r = 0.42; P = 0.018) and f-Dpyr (r = 0.49; P = 0.005) was observed. In the different disease subsets of AS, we found that patients with peripheral involvement had higher (f-Pyr + f-Dpyr) (P = 0.04) and f-Dpyr levels (P = 0.04), patients with early disease had elevated (f-Pyr + f-Dpyr) (P = 0.01), f-Dpyr (P = 0.02) and f-Pyr (P = 0.01) levels, and that those with raised ESR had enhanced f-Dpyr (P = 0.009) excretion. Patients were then stratified according to disease duration, peripheral involvement and sex, and this allowed us to observe that only urinary f-Dpyr remained elevated in patients independently from these variables and that raised ESR is the more relevant parameter for explaining this high level of excretion. CONCLUSION: We conclude that there was no difference in the levels of urinary pyridinium cross-links and beta-CTX between AS and controls. However, urinary excretion of some of these collagen compounds was enhanced in subgroups of AS, mainly in patients with raised ESR. Thus, AS patients with laboratory evidence of active disease could have a higher risk of bone loss. (+info)
Collagenase, cathepsin B and cathepsin L gene expression in the synovial membrane of patients with early inflammatory arthritis.
OBJECTIVE: To examine the expression of the matrix metalloproteinase, MMP-1, and the cysteine proteases, cathepsin B (CB) and cathepsin L (CL), in the synovial membrane (SM) of patients with early inflammatory arthritis. METHODS: Samples of SM were obtained by blind needle biopsy or needle arthroscopy from inflamed knees of 28 patients with early inflammatory arthritis (mean disease duration 10.2 months, range 2 weeks-18 months). Sixteen patients had rheumatoid arthritis (RA), nine psoriatic arthritis and there was one each with ankylosing spondylitis, gout and an undifferentiated arthritis. Comparison was made with tissue from two patients with established erosive RA and three normal synovial tissue samples. In situ hybridization was performed using digoxigenin-labelled RNA probes. RESULTS: MMP-1, CB and CL were expressed in all patients with early arthritis and in established erosive RA, whereas normal synovium showed only scanty expression. The three proteases were prominent in perivascular infiltrates and endothelial cells of early arthritis tissue. MMP-1 was observed primarily in the lining layer, but was also evident in the sublining area. CB and CL were expressed to a lesser extent in the lining layer, and were present mainly in the subintima. The three proteases were not found in lymphoid aggregrates. No differences were observed between the disease categories. CONCLUSIONS: The detection of MMP-1, CB and CL in the synovium shortly after symptom onset implies that the potential for joint destruction exists at a very early stage in the disease. In addition, the perivascular and endothelial cell expression suggests a role for these proteases in mononuclear cell influx to the inflamed synovium and in angiogenesis. (+info)