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Biomedical subjects

A Toivanen

Publications and source records attributed to A Toivanen.

At least 73 records · Page 4Linked to original sources

Familial scleroderma: HLA antigens and autoantibodies.

We report clinical and serological findings as well as the results of extended (HLA-A, B, C, DR and complotype) haplotype determinations of a family with two cases of systemic scleroderma and one case of primary biliary cirrhosis and incomplete CREST syndrome in a sibship of eight. In addition, one of these eight siblings has showed immunological findings of autoimmune disease for years but has not developed clinical symptoms. This family was studied by Soppi et al. in 1982; one member of the family has since then developed primary biliary cirrhosis and incomplete CREST type scleroderma. All family members with scleroderma or related disease as well as their sister with immunological abnormalities share the A2; B8; DR3 haplotype. Also some members of the family share the same haplotype but have remained healthy. This haplotype seems to be a predisposing factor but additional genetic or environmental factors are probably necessary for expression of autoimmune disease.

Adult↗

AB0 and Lewis blood groups in reactive arthritis.

In this study we evaluated secretor status in patients with reactive arthritis. Previous evidence indicates that non-secretion of AB0 and Lewis blood group antigens to saliva and other secretions is associated with susceptibility to certain bacterial infections and certain diseases with suspected autoimmune etiology. Secretor status can be determined based on the Lewis phenotype. We studied AB0, Lewis and Rhesus blood groups of 54 patients with previous reactive arthritis, 26 of whom had uroarthritis and 28 of whom had arthritis after enteric infection. Furthermore, 25 patients with uncomplicated yersiniosis and 57 healthy controls were studied. We did not find any correlation between secretor status and reactive arthritis or gastroenteritis due to Yersinia. AB0 blood group antigen B appeared to be protective against uroarthritis.

ABO Blood-Group System↗

Molecular mimicry in the pathogenesis of spondyloarthropathies. A critical appraisal of cross-reactivity between microbial antigens and HLA-B27.

We describe an amino acid homology between a virulence plasmid encoded outer membrane protein of Yersinia, YadA (previously called Yop1) and HLA-B27. This tetrapeptide is also included in the hexapeptide, earlier found to be identical between Klebsiella nitrogenase and HLA-B27. The synthetic peptide based on the HLA-B27 homologous portion of the YadA does not stimulate lymphocytes obtained from HLA-B27+ patients with Yersinia-triggered reactive arthritis or from controls. One-third of the yersiniosis patients have antibodies against the synthetic peptide. Instead of recognizing the HLA-B27 homologous portion, the antibodies are directed against the left flanking sequence of the synthetic peptide. Similar results were obtained regarding antibody response to Klebsiella nitrogenase derived synthetic peptide included in the panel of controls; the response was not restricted to patients with reactive arthritis nor was it specifically directed against the sequence shared by HLA-B27 and Klebsiella pneumoniae nitrogenase. The present results do not support the role of molecular mimicry or cross-reactive antibodies in the pathogenesis of spondyloarthropathies.

Adult↗

IgG and IgA antibody responses against porins in Yersinia-triggered reactive arthritis.

Using an enzyme immunoassay, the development and persistence of serum IgG and IgA class antibody responses against porins, a class of the major outer membrane proteins, were compared between patients who developed reactive arthritis and subjects who did not after Yersinia infection. A significant difference was seen between the two patient groups in the beginning of the disease: those with reactive arthritis had higher levels of IgG and IgA class antibodies against the porins. A similar difference in the IgA class antibodies was also seen at follow-up. This supports the hypothesis of persistence of the pathogen within the arthritic host.

Adolescent↗

Function of terminal ileum in patients with Yersinia-triggered reactive arthritis.

In order to study the function of the intestinal epithelium in the terminal ileum, the Schilling test was performed in 10 patients with Yersinia-triggered reactive arthritis, in 10 patients who had recovered from Yersinia enteritis without complications, and in five patients with rheumatoid arthritis treated with non-steroidal anti-inflammatory agents. The Schilling test indicates absorption of vitamin B12 in the terminal ileum, i.e. the area affected by Yersinia and inflamed in patients with reactive arthritis. The findings obtained demonstrate increased uptake through the epithelium in this area of the intestine in patients with Yersinia-triggered reactive arthritis. There are two possible explanations. First, Yersinia infection may have a long-term effect on the gut mucosa. Secondly, some individuals may, at the level of the terminal ileum, show enhanced absorption of vitamin B12 and/or other substances such as microbes or their components, resulting in increased susceptibility to certain infections.

Adult↗

Does reduced erythrocyte C3b receptor (CR1) activity contribute to the pathogenesis of yersinia triggered reactive arthritis?

Erythrocyte C3b receptor (CR1) activity was measured in 27 patients with yersinia triggered reactive arthritis and in 151 control subjects, including 36 patients with uncomplicated yersiniosis and 115 healthy subjects. CR1 was measured by the immune adherence haemagglutination method. Patients with yersinia triggered reactive arthritis had reduced levels of CR1 compared with the controls. This difference was mainly due to the finding that five out of six HLA B27 negative patients with arthritis had decreased CR1 activity. Such a quantitative difference may contribute to the pathogenesis of reactive arthritis by affecting the clearance of immune complexes.

Adult↗

Antibody response against 26 and 46 kilodalton released proteins of yersinia in yersinia triggered reactive arthritis.

Using an inhibition enzyme linked immunosorbent assay (ELISA) the serum antibody responses against released proteins of yersinia of molecular weights 26 and 46 kilodaltons were studied in 37 patients with and in 21 patients without reactive arthritis following yersinia infection. Although no difference was seen for the 46 kilodalton released protein, patients with yersinia triggered reactive arthritis had higher levels of antibodies against the 26 kilodalton released protein at the beginning of the disease than patients with uncomplicated yersiniosis. This may indicate an increased production of this protein in the early infection leading to poorer phagocytosis of the bacteria and thereby to the persistence of yersinia organisms within the arthritic host.

Adolescent↗

Synovial fluid leukocytosis in bacterial arthritis vs. reactive arthritis and rheumatoid arthritis in the adult knee.

In this comparative analysis of laboratory data, we examined the characteristics of synovial fluid leukocytosis in eighty adult patients with bacterial arthritis, reactive arthritis or rheumatoid arthritis of the knee joint. Synovial fluid leukocyte count and the percentage of polymorphonuclear cells seemed to perform well as a discriminator between bacterial infection and acute flare of the underlying disease in patients with rheumatoid arthritis. In contrast, there were no definite difference in the intensity of synovial fluid leukocytosis between patients with bacterial arthritis caused by living bacteria and patients with reactive arthritis probably caused by bacterial antigens.

Adolescent↗

Serum trace element concentrations and iron metabolism in allogeneic bone marrow transplant recipients.

Serum trace element concentrations, parameters of iron metabolism and serum protein concentrations were investigated in thirteen adult recipients of bone-marrow transplants receiving total parenteral nutrition. Six of the patients died during the four weeks follow-up. Serum zinc concentrations were initially low but increased during the treatment. They also tended to be lower in dying patients than in survivors. Concentrations of serum copper and selenium remained unaltered. Serum iron started to increase during the preconditioning and remained raised for three weeks. No significant changes occurred in serum transferrin levels. Transferrin saturation increased during the preconditioning and started to return to normal after day +14. Serum ferritin was greatly raised from the start and increased further during the procedure. Routine trace element substitution seemed to be sufficient during total parenteral nutrition with the possible exception of zinc. A return to normal transferrin saturation after day +14 may be an early favourable sign that the graft is taking and hematopoietic recovery commencing.

Adult↗

Combined use of released proteins and lipopolysaccharide in enzyme-linked immunosorbent assay for serologic screening of Yersinia infections.

An ELISA for the screening of serum antibodies to Yersinia species was developed using plasmid-encoded released proteins of Yersinia enterocolitica O:8 and lipopolysaccharide of Y. enterocolitica O:3 as a combined antigen. Of 43 sera from patients infected with one of six different Yersinia serotypes, 40 (93%) were positive in this assay. When tested using six serotype-specific ELISAs with the corresponding Yersinia bacteria as antigens, 38 (88%) were positive. This screening ELISA detects antibodies to all virulent yersiniae in one assay and offers the possibility for diagnosis of infections caused by Yersinia serotypes seen only occasionally and not usually included in the serotype-specific ELISAs. Thus, this ELISA offers a substantial advantage by saving time and money in routine laboratory work.

Adolescent↗

Bacterial antigens in synovial biopsy specimens in yersinia triggered reactive arthritis.

Non-viable structures of Yersinia enterocolitica O:3 were shown at the site of inflammation within mononuclear cells in the synovial membrane of eight out of 10 patients with yersinia triggered reactive arthritis. An avidin-biotin-peroxidase complex method, with a rabbit antiserum specific for Y enterocolitica O:3, was used to visualise yersinia structures. All 13 control samples were negative except for one with non-specific mast cell staining. The findings emphasise the significance of foreign material in the initiation of synovitis in reactive arthritis.

Adolescent↗

Intestinal permeability in patients with yersinia triggered reactive arthritis.

The passive intestinal permeability of patients with yersinia triggered reactive arthritis was studied using different sized polyethylene glycols (PEGs) contained in a mixture of PEG 400 and PEG 1000. The investigation was carried out at least one year after the onset of yersinia infection, and patients had neither acute gastrointestinal nor joint symptoms. The control groups included patients with uncomplicated yersiniosis as well as healthy subjects who were either HLA-B27 positive or negative. An altered intestinal barrier function to PEG molecules was detected in patients with a history of yersinia infection compared with healthy controls. No significant differences in the permeability were found between patients with or without reactive arthritis, nor was there any association of increased permeability with HLA-B27. The passive permeability of the intestinal mucosa to the larger molecules was increased for an unexpectedly long time after the acute yersinia infection, probably contributing to the perpetuation of joint symptoms in subjects susceptible to a chronic joint disease.

Adult↗

Salmonella lipopolysaccharide in synovial cells from patients with reactive arthritis.

Synovial cells from nine patients with reactive arthritis following Salmonella enteritidis or Salmonella typhimurium infection were examined for salmonella antigens. Extensive bacterial cultures of the synovial fluid were negative. Eight synovial-fluid cell samples stained positively on immunofluorescence with rabbit antisera against heat-killed S enteritidis or S typhimurium or with monoclonal antibodies specific for the causative salmonella lipopolysaccharide (LPS). Synovial tissue from the ninth patient stained positively in the avidin-biotin-peroxidase complex method with the monoclonal antibody. Control samples (synovial-fluid cells from thirteen patients with other rheumatic diseases and synovial tissue from two) were negative. Synovial cells from eight patients and five controls were studied by western blotting with the same monoclonal antibodies. Four of the eight patients but no controls had blots indicating salmonella LPS in the synovial cells. The presence of bacterial LPS in the joint is a common and pathogenetically important feature of reactive arthritis.

Acute Disease↗

Serologic evidence of Yersinia infection in patients with anterior uveitis.

Anterior uveitis is a common inflammatory eye disease associated with the HLA-B27 phenotype. Bacteriologic cofactors have been implicated in the pathogenesis of several diseases associated with HLA-B27. Using a sensitive enzyme-linked immunosorbent assay, we examined the incidence of previous Yersinia infection in a group of 28 consecutive patients with anterior uveitis. Twelve patients had a significantly increased antibody response to Yersinia, 8 of whom were HLA-B27 positive. Eight patients had IgM antibodies, possibly indicative of recent infection. There were no positive Yersinia serologic findings in our control group of 28 subjects, 13 of whom were HLA-B27 positive. A strong association was found between previous Yersinia infection and the development of anterior uveitis in HLA-B27-positive and HLA-B27-negative patients.

Adult↗

The immunological status of breast cancer patients during treatment with a new antiestrogen, toremifene.

The immune status of breast cancer patients was followed during antiestrogen treatment for at least 1 year or until progression of the disease. Twelve post-menopausal women with advanced estrogen-receptor-positive breast cancer were treated with a novel antiestrogen, toremifene. Immune functions were determined before the start of the treatment and at 3, 6, and 12 months. For NK cell cytotoxicity testing there were 74 healthy controls and for T cell subset measurements 28 healthy controls. No statistically significant changes in the T cell subsets or NK cell cytotoxicity were observed during treatment. However, throughout toremifene treatment patients had fewer CD4 cells (T helper lymphocytes) than did the controls. Cancer patients had higher pretreatment B cell values than the controls, P = 0.01, but during the first months of toremifene treatment B cell values decreased and remained within the normal range thereafter. A positive effect on mitogen-stimulation tests with phytohemagglutinin (PHA) and concanavalin A (ConA) was observed during the first months of treatment (P = 0.01 for PHA and 0.03 for log [ConA] and a stabilization at the higher level thereafter. These results indicate that toremifene has a stimulatory effect on cell-mediated immunity in breast cancer patients.

B-Lymphocytes↗