Search PubMed⌕ Search

Biomedical subjects

M Leirisalo-Repo

Publications and source records attributed to M Leirisalo-Repo.

At least 181 records · Page 10Linked to original sources

Phagocyte function in reactive arthritis.

The pathogenesis of reactive arthritis is multifactorial. The possible pathogenetic mechanisms include the role of microbial antigens which cross-react with the host tissue or trigger cytotoxic immune response. In addition an exaggerated inflammatory response of the host may contribute to the clinical picture of the acute arthritis and its late sequels. In this review, we present data showing that HLA-B27 positive subjects show enhanced neutrophil (PMN) migration and their sera support PMN migration more than HLA-B27 negative sera. Enhanced PMN function is persistent in patients with previous severe reactive arthritis or with late inflammatory sequels. In addition to hyperreactive PMNs, monocytes from patients with previous yersinia arthritis, but also from healthy HLA-B27 positive subjects, respond to stimulation with lipopolysaccharide by enhanced production of inflammatory monokines compared with HLA-B27 negative healthy controls. Thus, hyperreactive phagocytes can contribute to the severe inflammatory complications seen in patients with reactive arthritis. The primed phagocytes can also respond vigorously when stimulated either with endogenous mediators of inflammation or with endotoxin released during a new infection or as a sequel of change in the mucosal permeability described in patients with spondyloarthropathy.

Arthritis, Infectious↗

Clinical picture of reactive salmonella arthritis.

Twenty-three patients with reactive salmonella arthritis were treated at the Departments of Medicine (in 1970-1984) or at the Outpatient Department (in 1980-1986) of Meilahti Hospital. Nine different salmonella species were implicated as triggering factors. Salmonella was detected in 74% of the patients by stool cultures. Widal test was positive (greater than or equal to 1:160) in the remainder. The acute clinical picture was that of oligo or polyarthritis. Other musculoskeletal and inflammatory symptoms were frequent. The mean duration of the acute arthritis was 4.7 months (range 1.5-6.0). In 4 patients the disease ran a chronic course. The treatment of salmonella infection with chemotherapy had no obvious effect on the duration of the arthritis. In conclusion, salmonella arthritis is a form of seronegative spondyloarthritis, with acute features common to other types of reactive arthritides. The search for Salmonella should be included in the study of a patient with acute arthritis. Serology can be of help in patients with negative bacterial cultures.

Adult↗

Production of tumour necrosis factor and interleukin 1 by monocytes of patients with previous Yersinia arthritis.

We studied production of tumour necrosis factor (TNF) and interleukin 1 (IL-1) by using purified peripheral blood monocytes of patients with previous yersinia arthritis (YA) and of healthy HLA-B27 positive and negative controls. Lipopolysaccharide-exposed cells of HLA-B27 positive and negative patients, and those of HLA-B27 positive controls, generated significantly more TNF than did HLA-B27 negative control cells. There was a positive correlation between the levels of TNF and IL-1. Our results give credence to the view that augmented production of phlogistic mediators may contribute to inflammatory symptoms in patients with HLA-B27 associated disease.

Adult↗

Follow-up study of Reiter's disease and reactive arthritis. Factors influencing the natural course and the prognosis.

The acute clinical picture and long-term prognosis of 160 patients with Reiter's disease (RD), and 144 patients with reactive arthritis triggered by yersinia infection (YA), was analysed. Most of the patients with RD were men, while YA was as common among male and female patients. YA manifested in a third of patients as incomplete or complete RD. The long-term prognosis in RD was less favourable than in YA. Recurrent arthritis, development of chronic destructive arthritis and radiologic sacroiliitis were more frequent in RD than in YA. The presence of HLA-B27 was the major factor determining extra-articular inflammatory symptoms and the development of chronic problems.

Adolescent↗

Prenatal diagnosis of X-linked chronic granulomatous disease using restriction fragment length polymorphism analysis.

Prenatal diagnosis of X-linked chronic granulomatous disease (CGD) was performed with restriction fragment length polymorphism (RFLP) analysis using probes flanking the gene. The male fetus and an affected male displayed the same haplotype for RFLPs belonging to six linked loci extending from DXS164 to DXS7, which encompass the CGD locus, and for which the mother was heterozygous. Diagnosis of an affected fetus was confirmed after termination of the pregnancy by the study of fetal granulocytes using the nitroblue tetrazolium reduction test. In informative families prenatal diagnosis of CGD can be made earlier by RFLP analysis than by fetal blood sampling.

DNA↗

Antibody- and complement-dependent cell injury assayed by 51Cr release from human peripheral blood mononuclear cells pretreated with lipopolysaccharide.

Exposure of human peripheral blood mononuclear (MN) cells to deesterified (alkali-treated) lipopolysaccharide (LPS-OH) and then to 51Cr rendered the cells susceptible to 51Cr release in the presence of specific antibody and complement. The assay was optimized by using rough (Rb2 or Re) LPS. 51Cr release did not occur from cells preexposed to untreated or electrodialyzed LPS. Studies of isolated monocytes and lymphocytes revealed that the majority of the 51Cr released was derived from monocytes. The optimum concentration of LPS-OH was 10 micrograms/ml. Antiyersinia agglutinin-positive serum, but not a negative serum, obtained from patients with reactive yersinia arthritis caused 51Cr release from MN cells pretreated with yersinia LPS-OH. This implies that during yersinia infection antibodies are generated that can attack the cell membrane--LPS-OH complex. We conclude that the method provides a tool to demonstrate binding of LPS to MN cells in a manner that leads to cell injury in an immune host.

Adult↗

Antibody producing capacity to the bacteriophage phi X174 in yersinia arthritis.

Antibody production in response to the primary immunogen bacteriophage phi X174 was investigated in 14 patients with previous yersinia arthritis (YA) and in 15 controls. HLA-B27 occurred in 10 patients with YA and in three controls. After primary and secondary immunisation the antibody responses were essentially similar both in patients with YA and controls. Consequently our results suggest that antibody response to a foreign antigen does not differ between patients with YA and a normal control population. In addition, there was no difference in peak antibody responses between individuals with HLA-B27 and those without HLA-B27.

Adult↗

Polymorphonuclear leucocyte function and previous yersinia arthritis: enhanced chemokinetic migration and oxygen radical production correlate with the severity of the acute disease.

Polymorphonuclear leucocyte (PMN) functions (migration in vitro, chemiluminescence, O-2 production, binding of chemotactic peptide, and aggregation) were studied in HLA-B27 positive patients with previous yersinia arthritis (YA). PMNs of patients whose disease had been severe showed chemokinetic and chemiluminescence responses significantly higher than the PMNs of those with a mild disease. The results support the view that enhanced PMN function contributes to inflammatory symptoms in patients with YA.

Acute Disease↗

Aberrant phagocyte function in Shwachman syndrome.

Polymorphonuclear leucocytes (PMN) of patients with Shwachman syndrome show impaired mobility in vitro. We took this finding a step further by studying chemotaxis and chemiluminescence responses of purified PMN and monocytes (MO) of seven patients with Shwachman syndrome. Chemiluminescence responses of the patients' PMN were significantly increased, and thus impaired mobility may have derived from auto-oxidation of PMN. Chemotaxis of purified PMN was not impaired in a membrane filter, but it did become impaired when PMN were remixed with autologous mononuclear (MN) cells or MO. These cells always increased the migration of PMN. Because the patients' cells were fully capable of increasing the migration of control PMN, the defect most probably involved PMN. This is in harmony with the finding that the patients' purified PMN showed depressed chemotaxis under agarose. This suggests that for detecting impaired chemotaxis of purified PMN the assay conditions were more optimal in the agarose test than in the filter test. Both chemotaxis and chemiluminescence responses of the patients' MO were depressed, and thus, the defects involving PMN and MO are separate.

Agranulocytosis↗

Cell-mediated immune response in the diseased joints in patients with reactive arthritis.

To evaluate the level of lymphocyte activation in reactive and rheumatoid arthritis, density gradient-isolated, synovial fluid mononuclear cells were stained with a panel of antisera directed at lymphocyte activation markers using an avidin-biotin-peroxidase complex (ABC) method. More specifically, we studied the expression of immune response-associated class II HLA antigen (Ia), of receptors for interleukin 2 (Tac) and transferrin (T9), as well as of gp 40/80 glycoprotein (4F2). Although Ia+ cells formed about 60% of all the synovial fluid mononuclear cells in both disease conditions, the proportion of Tac+ (33 +/- 4% vs 3 +/- 1%, P less than 0.001), T9+ (34 +/- 4% vs 5 +/- 2%, P less than 0.001), and 4F2+ (48 +/- 6% vs 3 +/- 2%, P less than 0.001) cells was high only in reactive arthritis. All the patients who had reactive arthritis followed a favourable clinical course during the 4-month-long prospective follow-up, whereas disease activity was stable in patients with rheumatoid arthritis. These findings suggest that the diseased joints in reactive arthritis are a site for an active, but normally down-regulated, cell-mediated immune response.

Antibodies, Monoclonal↗

Immune function in patients with previous yersinia arthritis: lymphocyte responses to PHA and Staphylococcus aureus strain Cowan I.

Evidence has accumulated that, first, polymorphonuclear leukocytes (PMN) and humoral factors such as fragments of complement components may regulate immune response, and second, PMN function is enhanced in HLA-B27-positive subjects. We therefore used a whole-blood culture technique to study lymphocyte proliferation in response to phytohaemagglutinin-P (PHA) in blood samples obtained from patients with previous yersinia arthritis and from healthy subjects with or without HLA-B27. In another series of experiments, mononuclear cells were separated from peripheral blood and lymphocyte responses to Staphylococcus aureus strain Cowan I, a B-cell mitogen in fetal calf serum, and to PHA in pooled normal human serum were determined. The patients and the control subjects were always tested simultaneously. The results showed no significant differences between the subject groups. This suggests that humoral factors and enhanced neutrophil function do not exert remarkable effects on in vitro lymphocyte responses to mitogens in HLA-B27-positive subjects.

Arthritis, Infectious↗

Yersinia arthritis, immune functions and histocompatibility antigens.

Secondary immune response to tetanus toxoid (TT), monocyte function, and generation of suppressor cells were studied in patients with previous yersinia arthritis (YA) and healthy controls. A comparison of HLA-B27 positive and negative subjects revealed that leukocytes from the former showed significantly higher responses to TT but not to a variety of other antigens in a lymphocyte proliferation test, and higher rates of migration in a leukocyte migration inhibition assay in the absence of TT. The enhanced migration of leukocytes supports the concept that hyper-reactive neutrophils contribute to inflammatory symptoms in HLA-B27 positive subjects, irrespective of previous YA. No correlation was found between HLA-DR specificities and YA. However, HLA-DR2/HLA-B7 was associated with high suppressor cell activity and low serum levels of anti-TT-antibodies. This accords with the view that HLA-DR antigens play a role in the regulation of immune response.

Adult↗

Anti-DNA antibodies: the choice of assays for routine diagnostic work.

Sixty-six sera from 23 patients with systemic lupus erythematosus (SLE), 26 sera from patients with rheumatoid arthritis (RA), and 22 sera from normal healthy subjects were tested for the presence of antibodies against native (ds) DNA by the Crithidia luciliae immunofluorescence test and by the Farr assay, and for the presence of antibodies against denaturated (ss) DNA by the enzyme-linked immunosorbent assay (ELISA). Anti-dsDNA antibodies were detected in 57% of the SLE patients by the Crithidia test and in 65% by the Farr assay. Two of the RA sera were positive in the Crithidia test, whereas all were Farr negative. Anti-ssDNA antibodies of IgG class could be detected in 74% of the SLE patients and in none of the RA sera, while anti-ssDNA antibodies of IgM class were found in 26% of the SLE patients and in one RA serum. There was a good correlation between the results of the Farr assay and the IgG-anti-ssDNA ELISA but no agreement was found between the results of the Farr assay and the Crithidia test. We also measured the amount of C-reactive protein (CRP) in the sera but no correlation was seen between the levels of CRP and anti-DNA antibodies. We conclude that the demonstration of anti-ssDNA antibodies of IgG class is a good screening method in the diagnosis of SLE, and that antibodies against native DNA should be determined, preferably both by the Crithidia test and the Farr assay to confirm the diagnosis and in the follow-up of the patients.

Antibodies, Antinuclear↗

Synovial fluid cells in Reiter's syndrome.

Synovial fluid cells in Reiter's syndrome were studied by cell subset specific monoclonal antibodies and avidin-biotin-peroxidase complex staining. Mean leucocyte count was 9842/mm3 (9.842 X 10(9)/l), and 71% of all cells were polymorphonuclear leucocytes. 26 +/- 11 (SEM)% and 47 +/- 5% of all mononuclear cells in synovial fluid were M1+ monocytes and Ia+ cells, respectively. T11+ T lymphocyte was the predominant synovial fluid mononuclear cell (61 +/- 8%) but, in contrast to the inflammatory joint effusions in rheumatoid arthritis, T4+ cells clearly outnumbered T8+ cells in Reiter's syndrome. Thus the synovial fluid in Reiter's syndrome contains the immunocompetent and accessory cells required for immune response, which in fact is activated as suggested by lymphocyte Ia expression. Furthermore, in contrast with rheumatoid arthritis inducer/helper cells with T4 phenotype seem to be involved preferentially in the local pathogenetic mechanisms in Reiter's syndrome.

Adult↗