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Biomedical subjects

M Leirisalo-Repo

Publications and source records attributed to M Leirisalo-Repo.

At least 19 recordsLinked to original sources
PubMed1996

A comparative study of HLA genes in HLA-B27 positive ankylosing spondylitis and HLA-B27 positive peripheral reactive arthritis.

OBJECTIVE: To determine whether HLA-B27 positive patients with ankylosing spondylitis (AS) and reactive arthritis (ReA) share additional HLA factors that confer disease susceptibility. METHODS: HLA class I antigens were typed serologically, and class II antigens molecularly, in samples taken from 33 patients with AS, 30 patients with ReA, and 55 healthy HLA-B27 positive controls. RESULTS: There was no major difference between the HLA alleles in AS and ReA patients, but deviations were observed when compared with healthy controls, especially between the antigens that were probably encoded by genes in the non-B27 chromosome. CONCLUSION: These results suggest that both HLA class I and class II genes may influence the pathogenesis of HLA-B27 positive ReA, whereas class I antigens seem to be the major additional genetic factors in HLA-B27 positive AS.

Adult↗
PubMed1996

Outcome in patients with early rheumatoid arthritis treated according to the "sawtooth" strategy.

OBJECTIVE: To investigate the outcome of early rheumatoid arthritis (RA) when treated according to the "sawtooth" strategy, and to compare the results with the findings of other studies. METHODS: In this prospective study, 142 patients with early RA were treated actively with slow-acting antirheumatic drugs (SAARDs) for an average of 6.2 years, and were closely monitored clinically. Several outcome measures were applied, and the results were compared with findings in previously described cohorts. RESULTS: The mean cumulative number of SAARDs used during the study was 3.3. Treatment changes were made because of inefficacy more often than because of adverse events. The percentage of patients whose disease entered remission increased with time to 32% (45 of 142). Only 24% of the patients (34 of 142) had deterioration to Steinbrocker functional class III or IV. The "sawtooth" treatment strategy seemed to improve the outcome of the patients with early RA. CONCLUSION: In the majority of patients with early RA, "sawtooth" therapy remains beneficial for at least 6 years. However, in one-fourth of the patients, the disease fails to respond to this drug treatment strategy.

Adolescent↗
PubMed1996

Heterogeneity of rearranged T cell receptor V alpha and V beta gene transcripts in synovial fluid T cells of HLA-B27 positive reactive arthritis patients.

To analyze the T cell receptor (TCR) V-alpha/beta gene usage by synovial fluid (SF) and peripheral blood (PB) T cells of HLA-B27+ reactive arthritis (ReA) patients. The TCR V-alpha/beta gene usage was determined by the polymerase chain reaction on freshly isolated SF and PB mononuclear cells (MNC) of five HLA-B27+ ReA patients. A total of 30 TCR V alpha and 23 V beta (sub)family specific primers in combination with a C alpha or C beta specific primer, respectively, were used. In five patients most of the TCR V alpha and V beta gene segments expressed by PB T cells were also detected in the paired SF samples. Although one patient showed an increased expression of TCR V alpha2 in SF when compared to PB, the SF samples showed a heterogeneous TCR V-gene repertoire similar to PB. Although this study was limited to a small group of patients, the apparent lack of a restricted TCR V-gene repertoire in SF does not support the involvement of a single or limited number of T cell subsets in the disease process of HLA-B27+ ReA patients.

Adult↗
PubMed1996

Affinity-purified cardiolipin-binding antibodies show heterogeneity in their binding to oxidized low-density lipoprotein.

Antiphospholipid antibodies in autoimmune sera have been shown to react with a complex of phospholipids (cardiolipin) and a plasma phospholipid-binding protein, beta 2-glycoprotein I (apolipoprotein H). The binding of these antibodies was inhibited by oxidized low-density lipoprotein (LDL) in sera from patients with systemic lupus erythematosus (SLE), suggesting cross-reactivity between antiphospholipid antibodies and antibodies binding to oxidized LDL. We purified antiphospholipid antibodies by cardiolipin-polyacrylamide column from seven SLE sera and studied the reactivity of eluted fractions with cardiolipin-beta 2-glycoprotein I complex and oxidized LDL (malondialdehyde-conjugated LDL) in solid-phase enzyme immunoassay. In four sera the binding of IgG antibodies to cardiolipin-beta 2-glycoprotein I complex and to oxidized LDL appeared in the same fractions, whereas in three sera reactivities against cardiolipin and oxidized LDL were observed, at least in part, in separate fractions. The binding to solid-phase cardiolipin was dependent on the presence of exogenous beta 2-glycoprotein I in all fractions. Our findings show that antiphospholipid antibodies are heterogeneous in their binding to oxidized LDL, indicating that these two antibodies may have different subspecificities. Some eluted fractions reacted only with oxidized LDL, and did not show binding to cardiolipin-beta 2-glycoprotein I complex, suggesting that the lipid part in the antigenic complex might be responsible for the cross-reactivity of these antibodies. Accordingly, the biological functions of antibodies against phospholipid-beta 2-glycoprotein I complex and antibodies against oxidized LDL may also be different.

Adult↗
PubMed1996

Painful ankle region in rheumatoid arthritis. Analysis of soft-tissue changes with ultrasonography and MR imaging.

PURPOSE: To establish the diagnostic usefulness of ultrasonography (US) and MR imaging in patients with rheumatoid arthritis (RA) suffering from prolonged pain in the ankle region, where plain radiography did not demonstrate any changes. MATERIAL AND METHODS: Seventeen patients were studied with 0.1 T MR imaging and with high-frequency US. Talocrural and subtalar joints (including talonavicular joints), and medial, lateral, and extensor tendons and their synovial sheaths were examined by MR and US. RESULTS: Abnormal findings were found by MR imaging and US in altogether 76% of the patients, by MR alone in 53%, and by US alone in 59%. In 41% of the patients, lesions were demonstrated only by one method. Talocrural and subtalar joints were the most often affected sites (41% each), followed by the peroneus tendon (23%). In the joints, the abnormal findings were interpreted as synovitis; in the tendon areas, mostly as tenosynovitis. MR and US were highly significantly concordant (p < 0.0001), but correlation with clinical features was poor. CONCLUSION: In patients with pain in the ankle region, US and MR imaging can contribute to the diagnosis and localization of the abnormality when the plain radiography is normal. Easily available and inexpensive US can be recommended as the first imaging method after plain radiography. Some divergence seems to exist between US and MR, and in complicated cases both methods are recommended.

Adult↗
PubMed1996

Chemiluminescence responses and chemotaxis of monocytes from patients with early rheumatoid arthritis.

We studied chemiluminescence (CL) responses and chemotaxis of monocytes of patients with early rheumatoid arthritis (RA) before starting anti-rheumatic drug treatment and correlated the data to 2-year prognosis of the patients. Luminol-enhanced CL responses of RA monocytes to N-formylmethionyl-leucyl-phenylalanine or to phorbol myristate acetate, and lucigenin-enhanced responses to opsonized zymosan particles were significantly higher than those of healthy control subjects. Distances of chemotactic, chemokinetic and random migration of RA monocytes were similar to those of control cells. High CL responsiveness correlated with seropositivity but not with presence of HLA-DR4 or that of erosions at 2-year follow-up. The results give credence to the view that monocytes are metabolically activated in early untreated RA, but increased respiratory burst activity does not predict early development of erosions.

Adult↗
PubMed1996

Is continuous intranasal salmon calcitonin effective in treating axial bone loss in patients with active rheumatoid arthritis receiving low dose glucocorticoid therapy?

OBJECTIVE: To investigate the efficacy of intranasal salmon calcitonin (sCT) in treating axial bone loss in patients with rheumatoid arthritis (RA) taking low dose glucocorticoids. METHODS: In this open, multicenter study 32 women with RA were treated one year with sCT 100 IU/day and calcium (Ca) 500 mg/day; 31 women were treated with Ca alone. Bone mineral density (BMD) was measured at the lumbar spine and proximal femur (femoral neck, Ward's triangle, trochanter) before sCT therapy and again after 6 and 12 months. RESULTS: Among valid completers treated with sCT and Ca (n = 26), the mean BMD increased at the lumbar spine (L1-L4), femoral neck, and Ward's triangle. In contrast, valid completers treated with Ca (n = 23) showed bone loss at the spine (L1-L4), femoral neck, Ward's triangle, and trochanter area. The differences of the changes in BMD were statistically significant between these groups at the femoral neck, Ward's triangle, and trochanter. There were no significant differences between groups in bone loss over 12 months at the lumbar spine (L1-L4), although analysis of the upper segment (L1-L2) suggested some possible benefit of sCT. CONCLUSION: Intranasal sCT (100 IU/day) appears to have beneficial effects on bone loss at the proximal femur in patients with active RA treated with low dose glucocorticoids for 12 months; longer studies are needed to exclude transient bone remodelling effects.

Administration, Intranasal↗
PubMed1995

Anticoagulant selection influences flow cytometric determination of CD11b upregulation in vivo and ex vivo.

We recently devised three-colour flow cytometric assay for evaluating expression of CD11b on neutrophils and monocytes in circulation. Artefactual upregulation of CD11b ex vivo was minimized by cooling blood samples on ice. In this communication we further characterize the method in terms of different anticoagulants. EDTA was less optimal than ACD or heparin because (i) saturating concentrations of CD11b antibody (clone D12) were not achieved with resting cells; (ii) CD11b fluorescence intensity of synovial fluid cells, i.e., in vivo activated cells expressing CD11b at high levels, was significantly lower in EDTA plasma, and (iii) EDTA mediated more cell damage at 37 degrees C, as determined by PI staining. The fluorescence data suggested that D12 antibody binding was dependent on divalent cations. Saturating concentrations in the presence of EDTA in medium were easily obtained with synovial fluid cells and peripheral blood phagocytes activated with chemotactic peptide FMLP, suggesting that cell activation decreased cation concentrations required for D12 antibody binding. Using another CD11b antibody (2MPL19c), whose binding proved to be cation independent, it was shown that CD11b upregulation was not affected by EDTA. ACD was superior to heparin and phenylalanylprolylarginyl chloromethyl ketone (PPACK), a thrombin inhibitor, because cell counts were significantly lower in heparinized samples in cold, and in PPACK-anticoagulated samples treated with LPS at 37 degrees C. Kinetics of L-selectin shedding was similar in heparin and ACD, suggesting that cell loss did not derive from differences in cell activation. In comparison of buffy coat cell assay and whole blood assay, neutrophil CD11b expression was similar but background fluorescence was significantly higher in whole blood preparations. This implies that nonspecific antibody binding may occur more in whole blood assay, whereas in the buffy coat cell assay, sample manipulation procedures may slightly increase CD11b antibody binding, but not control antibody binding. Finally, it was confirmed that warming from 0 degrees C, but not from room temperature, to 37 degrees C increased CD11b expression significantly on neutrophils, and it was further shown that monocytes undergo similar changes. Cooling did not upregulate CD11b, and completely prevented LPS-induced upregulation. In conclusion, the results support use of ACD in evaluating CD11b expression; if EDTA is used, it is important to make sure that binding of CD11b antibody selected does not require presence of divalent cations in medium.

Adult↗
PubMed1995

Sulfasalazine in the treatment of spondylarthropathy. A randomized, multicenter, double-blind, placebo-controlled study.

OBJECTIVE: To assess the efficacy and tolerability of sulfasalazine (SSZ) in the treatment of spondylarthropathy. METHODS: We conducted a 6-month randomized, placebo-controlled, double-blind, multicenter study of patients with spondylarthropathy whose disease had remained active despite treatment with nonsteroidal antiinflammatory drugs. Patients were treated with SSZ (3 gm/day) or placebo. The primary efficacy variables were the physician's and patient's overall assessments, pain, and morning stiffness. End points were analyzed in the intent-to-treat and completer patient populations; the time course of effect was analyzed in the completer patient population. RESULTS: Of the 351 patients enrolled, 263 (75%) completed the 6-month treatment period. The withdrawal rates were 35 (20%) and 53 (30%) in the placebo and SSZ groups, respectively. In the intent-to-treat analysis of end point efficacy, the between-treatment difference reached statistical significance only for 1 of the 4 primary outcome variables, the patient's overall assessment of disease activity, for which 60% of the patients taking SSZ improved by at least 1 point on a 5-point scale, in contrast to 44% of the patients taking placebo. Laboratory markers of inflammation also showed statistically significant change in favor of SSZ. In subgroup analysis, the most impressive effects were seen in patients with psoriatic arthritis, both for the 4 primary efficacy variables and for secondary efficacy variables such as the number of inflamed joints. Adverse events were more frequent in the SSZ group than the placebo group, but all were transient or reversible after cessation of treatment. CONCLUSION: The results of this study show that SSZ had greater efficacy than placebo in the treatment of active spondylarthropathy, notably in patients with psoriatic arthritis.

Adult↗
PubMed1995

TAP1 and TAP2 polymorphism in HLA-B27-positive subpopulations: no allelic differences in ankylosing spondylitis and reactive arthritis.

The polymorphic TAP1 and TAP2 genes encode subunits of the transporter that delivers peptides to the HLA class I molecules. Because the polymorphism of the TAP genes has been shown to affect peptide transport, it has been suggested that TAP genes are potential regulators of the immune response. We studied TAP1 and TAP2 polymorphism in two multifactorial HLA-B27-associated diseases, ankylosing spondylitis (N = 30) and reactive arthritis (N = 30), in order to establish whether TAP genes are involved in the different pathogenesis of these diseases. Healthy HLA-B27-positive individuals (N = 55) were chosen as the primary controls and 93 individuals represented the random Finnish population as secondary controls. We found differences between the random and HLA-B27-positive populations, thus suggesting that certain TAP alleles are prevalent in HLA-B27 haplotypes. No differences were found between the AS and ReA groups nor between either of them and the healthy HLA-B27-positive controls. Thus it seems unlikely that TAP polymorphism, ar the level studied, has a dominant role in the pathogenesis of these diseases. However, a family study is needed in order to determine whether the same TAP complexes are carried by the same haplotypes in these diseases.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1995

Prognostic value of quantitative measurement of rheumatoid factor in early rheumatoid arthritis.

The prognostic value of quantitative measurement of rheumatoid factor (RF) by immunoturbidimetry was evaluated in 78 patients with early rheumatoid arthritis (RA) during a 3-yr follow-up. After starting disease-modifying antirheumatic treatment, a significant improvement in conventional clinical and laboratory variables measuring disease activity was observed, while a steady increase was found in radiological progression. Initial RF levels correlated with radiologically determined joint damage up to 3 yr, whereas no correlation of other initially determined conventional variables of disease activity was found. High levels of RF at entry and persistent RF positivity during the follow-up were markers for destructive disease. Initial RF positivity alone was a sensitive predictor for later joint destruction, but quantitative measurement of the initial RF level and especially repeated measurements of RF seemed to add significantly to the prognostic value of RF in distinguishing between progressive and non-progressive disease in early RA.

Adult↗
PubMed1995

Antibodies to Klebsiella pneumoniae, Escherichia coli and Proteus mirabilis in the sera of patients with axial and peripheral form of ankylosing spondylitis.

IgM, IgG and IgA class serum antibodies against the whole Klebsiella pneumoniae, Escherichia coli and Proteus mirabilis bacteria, as well as against K. pneumoniae and E. coli lipopolysaccharides (LPSs) were studied earlier in two separate patient populations of 99 and 85 patients with ankylosing spondylitis (AS) and in 102 healthy blood donors by enzyme immunoassay. In this study the patients were divided into groups according to the presence or absence of peripheral arthritis. The patients with peripheral type AS had increased levels of IgM and IgA class antibodies against K. pneumoniae, whereas the patients with axial type AS had increased levels of IgG and IgA class antibodies to K. pneumoniae, as well as IgA class antibodies against E. coli and P. mirabilis bacteria. Sulphasalazine treatment decreased the IgM and IgA class antibodies in peripheral AS and IgA class antibodies in axial AS against K. pneumoniae LPS. The antibody levels were also decreased against E. coli and P. mirabilis bacteria in the sera of patients with axial AS. The immunological findings in patients with peripheral and axial form of AS were different from each other and thus may reflect different aetiopathogenetic mechanisms for these two types of AS.

Antibodies, Bacterial↗
PubMed1995

Enteropathic arthritis, Whipple's disease, juvenile spondyloarthropathy, uveitis, and SAPHO syndrome.

During the past year, concepts of spondyloarthropathy and associated gut abnormalities have been further confirmed. In addition, the evolution of spondyloarthropathy to ankylosing spondylitis seems to be determined by the underlying gut inflammation. Other factors present early in spondyloarthropathy that affect the long-term prognosis of the disease have been determined. HLA-B27 has an impact on the severity of spondyloarthropathy. Its presence is also highly associated with uveitis. Paradoxically, HLA-B27+ uveitis is usually benign, with a good prognosis. A subgroup of patients can, however, have severe posterior uveitis; immunosuppressive drugs have been used to treat this disorder.

Adolescent↗
PubMed1995

IgA1 and IgA2 subclass antibodies against Klebsiella pneumoniae in the sera of patients with peripheral and axial types of ankylosing spondylitis.

OBJECTIVE: To study further the Klebsiella specific serum antibody response in patients with axial and peripheral types of ankylosing spondylitis (AS). METHODS: IgA1 and IgA2 subclass antibodies to Klebsiella pneumoniae were measured by enzyme linked immunosorbent assay in the sera of 171 patients with axial or peripheral type AS, and in sera of 100 healthy controls. The effect of 26 weeks of sulphasalazine treatment on the antibody levels in the two types of AS was also analysed. RESULTS: K pneumoniae specific antibody levels of both IgA1 and IgA2 subclasses were increased in the sera of patients with AS compared with healthy controls. The increased levels were present in patients with axial and with peripheral AS, and there were no statistically significant differences in the antibody levels between these two groups. Sulphasalazine treatment decreased the Klebsiella specific antibody level of IgA1 subclass in patients with axial AS, but there were no statistically significant changes in the IgA2 subclass, or in the patients with peripheral type AS. CONCLUSIONS: These results agree with earlier published findings suggesting that IgA (especially Klebsiella specific IgA) may have a role in the pathogenetic mechanisms of both peripheral and axial types of AS. In addition, it seems that both IgA1 and IgA2 subclasses are involved in the disease process.

Adolescent↗
PubMed1995

Comparison of intramuscular gold and sulphasalazine in the treatment of early rheumatoid arthritis. A one year prospective study.

We compared the effects of intramuscular gold and sulphasalazine on early, active rheumatoid arthritis in 128 consecutive patients. Intramuscular gold was started in the first 70 consecutive patients and sulphasalazine in the subsequent 58 patients. The patient groups were comparable with regard to clinical characteristics. In both groups clinical and laboratory parameters improved, but there was no significant difference between the two groups. The clinical improvement was most pronounced during the first three months. However, despite the clinical improvement a clear progression in radiological changes was observed in both groups, 40% of the patients taking gold and 48% of patients taking sulphasalazine discontinued the treatment because of adverse drug reactions or inefficacy during the one year follow-up. Adverse drug reactions were the main reason in both groups. These findings suggest that intramuscular gold and sulphasalazine seem to have an equal, positive effect on symptoms and clinical variables, but that radiological progression does occur in most patients none the less.

Adult↗
PubMed1995

Production of TNF by monocytes of patients with early rheumatoid arthritis is increased.

We studied the production of tumour necrosis factor alpha (TNF) by monocytes of patients with early rheumatoid arthritis (RA) before starting disease modifying anti-rheumatic drug treatment and a median 6 months (range 5-11 months) later, and correlated the pre-treatment results with 3-year prognosis. Monocytes of patients (n = 14) and controls (n = 14), isolated by the density gradient centrifugations, were cultured for 24 h with Escherichia coli lipopolysaccharide (LPS) 0-10 micrograms/ml. Before treatment, levels of TNF were higher in LPS-stimulated RA monocyte cultures than in the control cultures; differences were statistically significant in LPS 10 and 0.01 micrograms/ml. At 6 months, respective differences were not significant. Levels of TNF before treatment did not correlate to clinical or laboratory parameters of inflammation, or development of erosions. The results indicate that monocytes of patients with early RA are primed, and that the state of priming decreases during treatment.

Adult↗