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Biomedical subjects

M Leirisalo-Repo

Publications and source records attributed to M Leirisalo-Repo.

At least 199 records · Page 11Linked to original sources

Neutrophil function and HLA-B27. Superoxide production and yersinicidal activity of neutrophils from patients with previous yersinia arthritis.

Ankylosing spondylitis and reactive arthritis triggered by either enteritis or urethritis are both associated with human leucocyte antigen (HLA) B27. The pathogenesis of these diseases is not known, but it may involve immune function and inflammatory responsiveness of the host. Evidence has accumulated that neutrophils of HLA-B27 positive subjects show high chemotactic responses both in vitro and in vivo. Such a hyperreactivity may result in an exaggerated inflammatory response and thereby contribute to the pathogenesis of HLA-B27 associated diseases. We have extended the studies of phagocyte function by examining superoxide production and yersinicidal activity of neutrophils from patients with previous yersinia arthritis; the results show no gross differences, between patients and healthy subjects on one hand and between subjects with and without HLA-B27 on the other.

Arthritis↗

Exaggerated inflammatory responsiveness plays a part in the pathogenesis of HLA-B27 linked diseases--hypothesis.

Ankylosing spondylitis, acute anterior uveitis and reactive arthritides, including enteroarthritis and uroarthritis , are all associated with the human leucocyte antigen (HLA) B27. The pathogenesis of these diseases is not known, but it may involve inflammatory responsiveness of the host. In an acute inflammatory reaction, neutrophils are considered to cause tissue injury by both liberating lysosomal enzymes and generating toxic oxygen-derived free radicals. Furthermore, they may regulate both capillary permeability and the rate of vasodilatation at the site of inflammation. Evidence has accumulated that neutrophil responses to a phlogistic stimulus are enhanced in HLA-27 positive subjects. We suggest that hyperreactive neutrophils trigger a vicious circle of inflammation and render the subjects susceptible to exaggerated tissue injury.

Arthritis↗

Reactive arthritis.

Reactive arthritis (ReA) was known as Reiter's disease or Fiessinger-Leroy disease for nearly 100 years. However, during the past 30 years the disease has been known as reactive arthritis, a member of the spondyloarthritis family. Despite knowing the initiating event (infection) and genetic constitution (many patients have HLA-B27) of ReA, a model of interplay between environment and genetics, its pathogenesis is still incompletely known. This review covers the epidemiology, clinical features, treatment, and prognosis of ReA.

Adult↗

Circulating soluble interleukin-2 receptor level predicts remission in very early reactive arthritis.

OBJECTIVES: To assess the predictive value of serum soluble interleukin-2 receptor (sIL-2R) levels in patients with acute reactive arthritis (ReA). METHODS: The study includes 26 patients with acute ReA who had participated in a prospective population-based cohort study of very early arthritis. The patients had had arthritis of at least one joint with a maximum duration of 3 months. They were assessed by a rheumatologist on presentation and 6 months later. Serum sIL-2R levels on presentation were measured by the Immulite automated immunoassay analyser. Remission at 6 months, defined by the absence of swollen and tender joints, was related to the baseline sIL-2R level using a permutation test with general scores. Bootstrap estimation was used to derive the 95% confidence interval (CI). RESULTS: A total of 17 patients (65%) were in remission at 6 months and nine patients (35%) still had joint symptoms. In patients reaching remission within 6 months, the mean baseline sIL-2R level, 891 U/mL (95% CI: 658 to 1123), was higher than in patients not reaching remission, 501 U/mL (95% CI: 436 to 566), p = 0.022. CONCLUSIONS: A high serum sIL-2R level at baseline is a predictor of remission in patients with acute ReA.

Acute Disease↗

Infectious causes of death in patients with rheumatoid arthritis: an autopsy study.

OBJECTIVE: To study mortality from infections and accuracy of pre-mortem diagnoses in patients with rheumatoid arthritis (RA) autopsied during a 40-year period. METHODS: We investigated infectious causes of death, findings at autopsy, and clinicians' estimation of cause of death in 369 consecutively autopsied RA and 371 autopsied non-RA patients with same sex, age at death, and year of autopsy. We also compiled clinical features of RA patients from medical records available and examined the association between these and infectious causes of death. RESULTS: Deaths from any infection were more frequent in RA (36%) than in non-RA (26%) patients. In both groups, respiratory and urinary tract infections were the most common infectious causes of death. More RA patients died from urinary tract infections than non-RA patients. In approximately half of the patients in both groups, infection as a cause of death was unrecognized before death, with no major change occurring over the 40-year study period. CONCLUSIONS: Infections, especially respiratory and urinary tract infections, are frequent causes of death in RA patients. The high proportion of undiscovered infections as a cause of death highlights the diagnostic difficulty. With a decreasing number of autopsies being performed at present, greater numbers of infections may be under-reported.

Aged↗

The significance of serum anti-Borrelia antibodies in the diagnostic work-up of uveitis.

PURPOSE: To assess the utility of testing uveitis patients for anti-Borrelia antibodies in an area endemic for Lyme borreliosis. METHODS: We examined 161 uveitis patients for serum antibodies to Borrelia burgdorferi by Lyme ELISA. Antibodies were determined in patients with uveitis of unknown etiology and non-selectively from patients with an established diagnosis. RESULTS: Concentrations of antibodies to B. burgdorferi were elevated in 26 uveitis patients (16.1%), with elevated IgG in 11 of them (6.8%). In four of these patients Lyme borreliosis was a highly suggestive cause of uveitis because of a history of tick bites, systemic symptoms, response to antibiotic therapy, and/or a positive polymerase chain reaction result. Other causes of uveitis were ruled out. All these patients had vitritis. CONCLUSIONS: Non-selective testing of uveitis patients for Lyme antibodies is not reasonable even in endemic areas. We recommend using the Borrelia antibody test only in cases of uveitis of unknown cause, especially in patients with vitritis or other symptoms of Lyme borreliosis.

Adolescent↗

Occurrence of chronic inflammatory rheumatic diseases among parents of multiple offspring affected by juvenile idiopathic arthritis.

OBJECTIVE: The rarity of reports on extended multiplex families points out that the genetic component in juvenile idiopathic arthritis (JIA) might not be particularly strong. Our objective was to determine the frequency of chronic inflammatory rheumatic diseases among the parents who had two or more offspring affected by JIA. METHODS: During the last 17 years patients with JIA treated at the Rheumatism Foundation Hospital in Heinola and their parents have been systematically asked about the familial occurrence of rheumatic diseases. A total of 45 families with more than one sibling affected by JIA were found among about 2,300 JIA cases. In these "multicase families", 9 parents from 8 families also had a diagnosis of chronic inflammatory rheumatic disease. Their case histories were studied. RESULTS: Four of the parents had had JIA (one subsequently developed ankylosing spondylitis), and 4 had rheumatoid factor-negative chronic arthritis (one had also had chronic iritis since the age of 10, resembling that seen in JIA). Three of them had features of JIA and only one met the classification criteria for rheumatoid arthritis. One had ankylosing spondylitis. CONCLUSIONS: Since the expected number of JIA cases among the 90 parents was about 0.2, there was drastic increase in JIA frequency among the parents in families with multiple offspring also affected by JIA. These results suggest that JIA susceptibility genes may likely be clustered in these families.

Adolescent↗

Serum soluble interleukin-2 receptor predicts early remission in patients with recent-onset rheumatoid arthritis treated with a single disease-modifying antirheumatic drug.

OBJECTIVE: To study the value of baseline serum levels of circulating soluble interleukin-2 receptor (sIL-2R) and soluble E-selectin as predictors of early remission in patients with recent-onset rheumatoid arthritis (RA) receiving a single disease-modifying anti-rheumatic drug (DMARD) (SINGLE) or therapy with a combination of DMARDs (COMBI). METHODS: Baseline (n = 157) serum samples originate from the FIN-RACo (FINnish Rheumatoid Arthritis Combination therapy) trial, in which 195 patients with early and clinically active RA were randomly assigned to receive either SINGLE (initially sulfasalazine) with or without prednisolone, or COMBI therapy (sulfasalazine, methotrexate, hydroxychloroquine, and prednisolone). Of the samples, 76 were from SINGLE patients and 81 from COMBI patients. sIL-2R was measured by automated immunoassay analyzer and sE-selectin by enzyme-linked immunosorbent assay. RESULTS: At six months, 7 (9% [95% CI: 4 to 18]) SINGLE and 19 (23% [95% CI: 15 to 34]) COMBI patients were in remission. In multivariate logistic regression analysis, sIL-2R <442 U/ml and COMBI therapy were the only predictors of remission. The area under receiver operating characteristic curve for sIL-2R level was 0.86 (95% CI: 0.62 to 0.95) in SINGLE and 0.57 (95% CI: 0.42 to 0.71) in COMBI (p = 0.006). In SINGLE, the optimal cut offpoint was 442 U/ml, lower levels predicting remission with sensitivity of 83% (95% CI: 73% to 91%) and specificity of 86% (95% CI: 42% to 100%). Likelihood ratio for positive test was 5.9 (95% CI: 1.6 to 32.8). In multivariate logistic regression analysis, sIL-2R <442 U/ml and COMBI therapy were the only predictors of remission. CONCLUSION: Low baseline serum sIL-2R level predicts early remission of patients with active early RA treated with a single DMARD.

Adult↗

Effectiveness of different cryotherapies on pain and disease activity in active rheumatoid arthritis. A randomised single blinded controlled trial.

OBJECTIVE: Local cryotherapy is used to relieve pain and inflammation in injuries and inflammatory conditions. Whole-body cryotherapy is an extreme method administered at -110 degrees C for 2 to 3 minutes. The aim of the study was to compare the effect of cryotherapies on pain and inflammation in patients with rheumatoid arthritis (RA). METHODS: Sixty patients with active seropositive RA were recruited in a randomised controlled single-blinded study to receive whole-body cryotherapy at -110 degrees C, whole-body cryotherapy at -60 degrees C, application of local cold air at -30 degrees C and the use of cold packs locally. In the final analysis, the last 2 groups were pooled. The patients had 2-3 cryotherapy sessions daily for one week plus conventional physiotherapy. Clinical and laboratory variables and patient's and physician's global assessments were used to assess the outcome. Disease activity was calculated by DAS. RESULTS: Pain decreased in all treatment groups, most markedly in the whole-body cryotherapy (-110 degrees C) group. DAS decreased slightly with no statistically significant differences between the groups. No serious or permanent adverse effects were detected. Six of 40 patients (15%) discontinued the whole-body cryotherapy. CONCLUSION: Pain seemed to decrease more in patients in the whole-body cryotherapy at -110 degrees C than during other cryotherapies, but there were no significant differences in the disease activity between the groups. However, cryotherapy at -110 degrees C is expensive and available only in special centres and may have minor adverse effects. Based on our results, whole-body cryotherapy at -110 degrees C is not superior to local cryotherapy commonly used in RA patients for pain relief and as an adjunct to physiotherapy.

Adult↗

Association of tumour necrosis factor a, b and c microsatellite polymorphisms with clinical disease activity and induction of remission in early rheumatoid arthritis.

OBJECTIVE: To study the associations of tumor necrosis factor (TNF) a, b and c microsatellite markers with 1) the clinical disease activity and 2) the induction of remissions in patients with early rheumatoid arthritis (RA) treated with two treatment strategies. METHODS: In the FIN-RACo (FINnish Rheumatoid Arthritis Combination therapy) trial of two years, 195 patients with recent-onset RA were randomly assigned to receive either a combination (COMBI) (sulphasalazine, methotrexate, hydroxychloroquine, and prednisolone) or a single (SINGLE) (initially sulphasalazine with or without prednisolone) disease modifying antirheumatic drug (DMARD) therapy. TNF a, b and c microsatellite and HLA-DRB1 typings were carried out in 165 (79 COMBI; 86 SINGLE) study completers. RESULTS: At baseline the 28 joint disease activity scores (DAS28) of the patients positive for TNFa2, a13 or b1 microsatellite markers were significantly higher than in the other patients. In the SINGLE patients the DAS28 improved comparably in patients with (n = 31) or without (n = 53) the TNFb1 marker (NS), while the DAS28 of the TNFb1-positive COMBI patients (n = 22) improved significantly more than that of the TNFb1-negative cases (n = 57) (p = 0.014). Respective 31.8% (7/22) and 28.1% (16/57) of the COMBI patients with or without TNFb1 allele achieved remission at one year. The corresponding figure in SINGLE patients were 0% (0/31) and 20.8% (11/53) (p = 0.006). At two years the remission frequencies in the TNFb1+/TNFb1- patients in the COMBI and SINGLE were 50.0%/38.6% and 9.7%/22.6%, respectively. CONCLUSION: Early TNFb1+ RA patients have more active disease but respond more favourably to COMBI treatment than the patients without this microsatellite allele. The finding may be of clinical relevance for the choice of DMARDs in early RA.

Adolescent↗

Depressed cutaneous cell-mediated immunity in early rheumatoid arthritis.

To study the role of cellular immunity in recent-onset rheumatoid arthritis (RA), 26 patients with early RA were examined by skin testing with seven common recall antigens. The skin test was performed before the administration of second-line antirheumatic therapy and was repeated after six months of medication. Controls included healthy individuals and patients without known immunological abnormalities or malignancies. 50% of the RA patients were classified as anergic compared to 7% of the controls. In the RA patients, depression of cell-mediated immunity was related to gender but not to disease activity. Anergic and reactive patients showed similar clinical improvement after six months of therapy. The frequency of anergy at six months was not statistically different from that before therapy. HLA-DR4 was more frequent in the reactive patient group (92%) compared with anergic patients (53%). We conclude that cell-mediated immunity is impaired in early RA but the impairment does not correlate with disease activity or with the response to treatment and does not return to normal during treatment with second-line antirheumatic drugs.

Adult↗

Effects of HLA-B27 positive and negative sera on migration of polymorphonuclear leukocytes in vitro.

Sera from both HLA-B27 positive patients with previous yersinia arthritis and healthy HLA-B27 positive subjects have been reported to stimulate chemokinetic migration of polymorphonuclear leukocytes (PMNs) more than sera from subjects who are HLA-B27 negative. To study this further we tested chemotactic and chemokinetic activities of sera of 213 consecutive blood donors (27 positive for HLA-B27, 12.7%) and those of 55 children (mean age 20 months, range 6-137 months, 8 positive for HLA-B27, 14.5%). Migration distances of PMNs both in membrane filter and under agarose were longer, although not in a statistically significant way, in HLA-B27 positive adult sera than in HLA-B27 negative ones. Chemokinetic activity of sera of HLA-B27 positive children was very similar to that of HLA-B27 negative children. These results give credence to the view that PMN migration enhancing capacity of HLA-B27 positive sera described previously is acquired secondarily and is not genetically determined.

Adult↗

Sonographic analysis of enthesopathy in the lower extremities of patients with spondylarthropathy.

OBJECTIVE: Enthesopathy is one of the features characterizing patients with spondylarthropathies. Its diagnosis is usually based on clinical symptoms such as the presence of calcanear pain or tenderness at the insertion(s) of ligaments. More objective ways to estimate the presence and nature of enthesopathy are needed. Therefore, we analysed both by clinical and sonographic methods the presence of enthesopathy in the lower extremities of patients with spondylarthropathy. METHODS: 31 consecutive patients with spondylarthropathies (15 with reactive arthritis, 12 with ankylosing spondylitis, and 4 with psoriatic arthritis) were studied for the presence of enthesopathy in the lower extremities, independently by clinical examination and by high resolution sonography. RESULTS: Sonography detected inflammatory lesions in 44 entheses of 20 patients. Oedema at the insertion of the tendon was the most common finding. Signs of enthesitis were more common in the lower portion of the leg. In addition to enthesitis, bursitis was a common finding by sonography. By clinical examination, enthesitis was diagnosed in 56 sites in 20 patients, most frequently at the insertions of the Achilles tendon and the plantar fascia. Bursitis around the calcaneus and synovitis/pain in the hip and knee joints were most frequently misinterpreted to indicate enthesopathy at the clinical examination. In addition, half of the insertions with only oedema at sonography were clinically asymptomatic. CONCLUSIONS: Sonographic examination of ligamentous insertions offers morphologic information which is unobtainable by the clinical judgement of tenderness in the estimation of enthesopathy in patients with spondylarthropathies.

Adult↗

Anti-RA 33 as a marker antibody of rheumatoid arthritis in a Finnish population.

To obtain information on anti-RA 33 as a marker antibody of rheumatoid arthritis (RA), a panel of Finnish sera were tested by immunoblotting with partially purified RA 33 antigen. Six of 100 specimens from patients with RA, one of 39 specimens from subjects who later developed seropositive RA, and one of 50 specimens from subjects with "false-positive" rheumatoid factor reactions were positive. The findings are compatible with the concept that anti-RA 33 is associated with RA from its onset and can even precede the disease. However, the prevalence of this antibody in Finnish RA patients is remarkably low compared to patients from continental Europe.

Adult↗

Gliadin immune reactivity in patients with rheumatoid arthritis.

OBJECTIVE: To investigate whether patients with rheumatoid arthritis (RA) have immunological or clinical evidence of gluten hypersensitivity. METHODS: Antigliadin antibodies (AGA) and antireticulin antibodies (ARA) were determined in two groups of RA patients and in a control group of patients with spondylarthropathies. In the first group of 42 patients with recent-onset RA, AGA and ARA were studied longitudinally during a one-year follow up period. In the second group of 36 patients with advanced RA and various abdominal symptoms examined by upper gastrointestinal endoscopy, AGA and ARA were determined cross-sectionally. RESULTS: Increased AGA (IgA or IgG) levels were found in 37% (29/78) of all RA patients compared to 12% (3/25) of controls. ARA positivity (IgG) was found in 4% (3/78) of RA patients and in none of the controls. AGA positivity was increased in patients with early RA compared to patients with advanced disease (48% vs. 25%) but the difference was not statistically significant. However, no true gluten hypersensitivity with positive AGA and ARA together with villous atrophy was observed. CONCLUSION: Despite the increased AGA positivity found distinctively in patients with recent-onset RA, none of the RA patients showed clear evidence of coeliac disease. AGA positivity in early RA may indicate a role of the gut immune system in the initiation of RA.

Adult↗

Persistence of enthesopathic changes in patients with spondylarthropathy during a 6-month follow-up.

The persistence of enthesopathic changes was studied by ultrasound (US) in 23 patients with spondylarthropathy during a 6-month prospective trial with sulphasalazine (Salazopyrin). During the follow-up significant improvement was seen in the joint symptoms and in the laboratory variables. By US 78% of the patients had enthesopathy at entry and 74% after 6 months of follow-up. The plantar fascia was the enthesis most frequently affected. Treatment with sulphasalazine had no obvious influence on the persistence of enthesopathy. Enthesopathy is as a rule a constant phenomenon and is probably caused by chronic enthesitis. A parallel resolution of anatomic soft tissue changes and the clinical status was not seen on US. There was also no evidence of a favourable effect of sulphasalazine on enthesopathy in the 6-month follow-up.

Adult↗