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Biomedical subjects

A Karlsson-Parra

Publications and source records attributed to A Karlsson-Parra.

At least 55 records · Page 3Linked to original sources

A study of autoimmune gastritis in the postpartum period and at a 5-year follow-up.

The presence of autoimmune gastritis was investigated in 54 women with postpartum thyroiditis. Parietal cell antibodies (PCA) specific against H+, K(+)-adenosine triphosphatase (EC 3.6.1.36) were found in 18 women during pregnancy; in 10 of them, a 2-9-fold increase in the PCA level was observed in the postpartum period. At a 5-year follow-up, the initially PCA-positive women still had elevated antibody levels. Hypergastrinemia and low pepsinogen levels were noted in 4 women. In 2 of these women low serum vitamin B12 levels had developed. In 6 of 9 PCA-positive women examined by gastroscopy, biopsy specimens from the gastric body mucosa contained mononuclear cells, mainly T lymphocytes (CD3+) and macrophages (Leu-M3+) combined with an aberrant epithelial expression of HLA-DR. In four patients with chronic gastritis, all parietal cells, as defined by a specific monoclonal antibody, were found to have immunoglobulin G (IgG) deposits by a double-immunostaining method. Three of them had microscopic evidence of atrophy, whereas in 1 patient the body mucosa was intact. In 1 further patient with intact glands at histological examination, the basolateral membrane of some oxyntic glands was coated with IgG. The selective in situ deposition of antibodies associated with histologically intact parietal cells may support the concept that specific autoantibodies participate in the early pathogenesis of parietal cell destruction.

Adenosine Triphosphatases↗

T-cell receptor V-gene usage in synovial fluid and synovial tissue from RA patients.

The question of whether there is a preferential use of certain V genes in T cells entering an inflamed joint has hitherto been studied mainly using unfractionated cells from synovial fluid and tissue respectively, and no clear answer to the question has yet been provided. Concomitantly, evidence has been provided that the use of V genes may differ considerably between CD4+ and CD8+ T cells, and consequently that detection of biased V-gene expression within an inflammatory lesion may require separate analysis of the two T-cell subsets. In this paper we have therefore studied T-cell receptor V-gene expression in rheumatoid arthritis by means of double stainings of synovial fluid and blood for available anti-TCR monoclonal antibodies and antibodies to CD4 and CD8, respectively. Double stainings were also performed with anti-TCR antibodies and antibodies to activation markers HLA-DR and IL-2R. A certain bias towards the preferential use of certain V genes was seen particularly in the synovial fluid samples within both the CD4+ and CD8+ T-cell populations, but no uniform pattern was evident among the 35 patients investigated.

Arthritis, Rheumatoid↗

Cyclic variation of major histocompatibility complex class II antigen expression in the human fallopian tube epithelium.

OBJECTIVE: To systematically investigate the expression of major histocompatibility complex (MHC) class II antigens (human leukocyte antigens, HLA-DR, -DP, and -DQ) on columnar epithelium in the fallopian tube during the menstrual cycle. STUDY DESIGN: Biopsies were collected from the fallopian tube during laparotomy sterilization and immunoperoxidase staining was performed. SETTINGS: Departments of Gynecology and Obstetrics and Clinical Immunology and Transfusion Medicine, Uppsala University, Uppsala, Sweden. PATIENTS: Twenty healthy fertile women undergoing sterilization at different times of the menstrual cycle. INTERVENTIONS: None. MAIN OUTCOME MEASURES: The staining of the columnar epithelium was judged on a 4-graded scale according to the distribution of class II antigens. RESULTS: A widespread preovulatory HLA-DR expression was observed almost completely lining the columnar epithelial cells including the luminal surface, whereas postovulatory the HLA-DR expression was withdrawn from the surface. The HLA-DP and -DQ antigens varied in a similar way, although not as pronounced. CONCLUSIONS: The MHC class II antigen variation in the fallopian tube epithelium seen in this study may indicate a hormonal regulation that could reflect variable need for local immunocompetence during the menstrual cycle: a preovulatory need for immunoreactivity against invading microbes and postovulatory an optimal survival of the foreign preimplantation embryo.

Epithelium↗

Rheumatoid arthritis.

The immunopathogenesis of rheumatoid arthritis is discussed in two ways. First, we consider the major question of whether T cells are likely to drive the disease. Second--and assuming T cells to be important--we discuss available data on the components of the trimolecular complex (major histocompatibility complex class II-antigen-T-cell receptor), which are possibly involved in the disease. Our two main points are that the most important questions concerning the pathogenesis of rheumatoid arthritis require answers from immunointervention in patients, and that animal experiments can be increasingly used in interpreting current experiments in humans.

Animals↗

Evidence that LS-2616 (linomide) causes acute rejection of rat allografts protected by cyclosporine but not of long-term surviving allografts.

The immunomodulator LS-2616 (Linomide) induces rejection of cyclosporine-protected rat cardiac allografts. The aim of this study was to characterize this rejection in the presence of CsA and to test LS-2616 in other models of permanent graft acceptance in the rat. PVG rat hearts were transplanted heterotopically to Wistar/Kyoto (Wi/Ky) rat recipients on day 0. The recipients were treated orally on days 0-9 with CsA (10-40 mg/kg) and/or with LS-2616 (2.5-160 mg/kg) starting at different times (day -7 -+5) until the day of complete rejection. The addition of LS-2616 (day -1--stop) to CsA (10 mg/kg) resulted in a dose-dependent antagonism of the immunosuppressive effect of CsA with daily doses of 2.5-160 mg/kg. Furthermore, the results were similar, irrespective of whether LS-2616 treatment (160 mg/kg) was started on day -7, -1, +1, +3, or +5. LS-2616 (160 mg/kg) pretreatment of the recipient for 7 days before transplantation was considerably less effective. CsA (20 mg/kg) for 14 days after a PVG to DA transplantation resulted in permanent graft survival. This was not abrogated by LS-2616. Neither was rejection induced in long-term surviving grafts of RT1.C incompatible Lewis recipients. Our data suggest that LS-2616 activates already stimulated and sensitized T cells that are otherwise controlled by CsA.

Animals↗

Use of chicken antibodies in enzyme immunoassays to avoid interference by rheumatoid factors.

Rheumatoid factor (RF) is a major source of interference in many immunoassays. Most immunoassays use mammalian polyclonal or monoclonal antibodies, and RF can react with IgG from mammalian species, thus causing false-positive results. In this work we have studied RF interference in a sandwich ELISA, where RF in the sample may react with both the capture antibody and the detection antibody to give a false-positive reaction. We show that rheumatoid factors do not react with chicken IgY; if the capture antibody or detection antibody (or both) is of avian origin, the interference of RF or other anti-IgG antibodies in sandwich ELISA can be avoided.

Animals↗

Autoantibodies to epithelial cells in patients on long-term therapy with leucocyte-derived interferon-alpha (IFN-alpha).

During routine screening for anti-nuclear antibodies, using rat liver tissue as substrate, a reactivity against bile duct epithelium was observed in sera from carcinoid tumour patients given human leucocyte-derived IFN-alpha (HuLe IFN-alpha). In a retrospective study, initiated by this observation, the development of serum antibodies to bile duct epithelium was observed in nine out of 12 patients with carcinoid tumours and in three out of 14 patients with hairy-cell leukaemia during their treatment with HuLe IFN-alpha. However, no bile duct reactivity was observed in sera from carcinoid or hairy-cell leukaemia in patients given recombinant IFN-alpha. When analysing the reactivity of positive sera against a panel of rat and human tissues, a uniform reactivity was observed against simple epithelial cells lining the gastrointestinal tract, pancreatic secretory ducts, fallopian tube, kidney tubuli, mesothelium and also against carcinoid tumour cells. The mechanisms promoting autoreactivity against this simple epithelial cell autoantigen is so far unknown. The cytoplasmic as well as the restricted staining pattern of simple epithelial cells may indicate autoreactivity against certain cytoskeletal intermediate filaments, such as cytokeratin 19, 18 and 8, known to be exclusively present in simple epithelial cells and tumours derived from them.

Animals↗

Presence of human 65 kD heat shock protein (hsp) in inflamed joints and subcutaneous nodules of RA patients.

Monoclonal antibodies to the human homologue of the bacterial 65 kD heat shock protein (hsp) were used to investigate the tissue distribution of endogenous hsp 65 in normal versus rheumatoid synovial tissue, in subcutaneous nodules of patients with rheumatoid arthritis (RA) and in several instances of non-rheumatoid inflammation. A strong reactivity of the anti-hsp antibody was found in the cartilage-pannus junction in rheumatoid joints and in rheumatoid nodules, but not in normal joints or in normal or inflamed kidney or liver (irreversible graft rejection, chronic glomerulonephritis or primary biliary cirrhosis). The findings provide a new hypothetical explanation for a role of T cells reactive with the 65 kD hsp in the generation of both articular and extra-articular lesions in chronic rheumatoid arthritis.

Antibodies, Monoclonal↗

The anti-Leu4 (CD3) monoclonal antibody reacts with proximal tubular cells of the human kidney.

A recent observation that certain kidney tubular cells, especially those in the normal kidney, were positively stained with the anti-Leu4 monoclonal antibody (MoAb) led us to investigate systematically the reactivity of three different anti-CD3 MoAb with a panel of normal human kidneys. Using immunohistochemical and immunofluorescence staining techniques, the anti-Leu4 MoAb was found to react with proximal tubular cells in all eight examined kidneys, while no tubular-cell reactivity was observed with the OKT3 or DAKO-T3 MoAb. In each kidney, however, all three antibodies reacted with a similar number of occasionally encountered T cells. The G11 MoAb, which has been reported to react with a calcium receptor-associated molecule, and the anti-Leu4 MoAb showed almost identical patterns of tubular-cell reactivity. The observed co-distribution of Leu4-expressing structures with a putative Ca2+ sensor in the kidney and the fact that binding of anti-Leu4 to T cells induces Ca2+-mediated signal transduction, warrant further studies on a potential role of Leu4-expressing structures in Ca2+ regulation of proximal tubular cells.

Antibodies, Monoclonal↗

Circulating class II transplantation antigen-expressing T lymphocytes in children with insulin-dependent diabetes mellitus at diagnosis.

The occurrence of circulating class II antigen-expressing T lymphocytes was examined in 25 children with insulin-dependent diabetes mellitus using an indirect double immunofluorescence assay on prefixed cell samples. In order to exclude sensitization to heterologous insulin as a possible factor affecting the results, the patients were investigated at the day of clinical onset, before receiving insulin. An increased percentage of T cells (CD3+ cells) expressing class II antigens was seen in 19 out of 25 patients and class II expression was observed on cells within both the CD4+ and CD8+ T cell subsets. No correlation was found between the levels of class II expressing T cells and the individual degree of metabolic derangement or indicators of recent infection. Re-testing of 16 patients after one year on insulin treatment revealed a significant decrease of class II expressing T cell levels. Our data suggest that the increased levels of class II expressing T cells seen in IDDM of recent onset directly reflects immune reactions that are related to the disease process.

Adolescent↗

Phenotypes of peripheral blood lymphoid cells in patients with asbestos-related pleural lesions.

Asbestos-related parietal pleural plaques develop slowly and are of little clinical significance. Other asbestos-related pleural reactions, for example acute exudative pleurisy and progressive pleural fibrosis, are of clinical importance. The pathogenesis of these reactions is unknown, but one hypothesis is that immunological disturbances are involved. To investigate this hypothesis a phenotypic characterization of lymphoid cells was performed in the peripheral blood of 45 patients with asbestos-related pleural lesions; 20 with pleural plaques (PP), 15 with diffuse pleural fibrosis (DPF), and 10 with benign asbestos pleural effusion (BAPE). Twenty-four healthy blood donors were used as controls. All asbestos groups together had a significantly higher percentage of B-cells than the controls. The percentage number of "helper/inducer" T-cells was significantly lower in the BAPE and DPF groups than in the control and PP groups. Thus, significant aberrations in peripheral blood lymphoid cells were found in patients with DPF and BAPE. This differed from patients with PP only who were similar to normals.

Aged↗

Immunological effects of ciclosporin in primary biliary cirrhosis: suppression of activated T cells and autoantibody levels.

The effects of ciclosporin (CS) on liver immunohistology and peripheral blood T lymphocyte distribution were studied in 5 patients with primary biliary cirrhosis (PBC) receiving CS treatment for 6 months. Several significant immunological changes were seen during the course of treatment: the numbers of infiltrating T cells (Leu4+) and HLA-DR+ cells (mainly macrophage/dendritic-like) within the lobule parenchyma decreased; the total circulating T cell numbers increased and the percentage of activated, HLA-DR-expressing Leu2a+ ('suppressor/cytotoxic') T cells and Leu3a+ ('helper/inducer') T cells decreased. Moreover, using a highly sensitive enzyme immunoassay for antimitochondrial antibody (AMA), a selective decrease of IgM-type (but not IgG-type) AMA levels was observed in 4 patients. A reversal towards pretreatment values was observed for all these immunological parameters 3-6 months after withdrawal of therapy. We conclude that CS may inhibit both cell-mediated and antibody-mediated autoimmune mechanisms operating in PBC.

Autoantibodies↗

HLA-DR antigen expression on T cells from cerebrospinal fluid in multiple sclerosis and aseptic meningo-encephalitis.

HLA-DR expression on T lymphocytes in cerebrospinal fluid (CSF) from patients with multiple sclerosis (MS) and acute aseptic meningo-encephalitis (AM), and from blood only from healthy controls was examined by a new double-immunofluorescence labelling assay using species-specific second layers on prefixed cell samples. Thirteen of 16 patients with AM (81%) had an elevated percentage of DR positive T cells in CSF against only two of 20 patients with MS (10%). Our data indicate that AM, an acute infection of the central nervous system (CNS), is accompanied by accumulation in CSF of activated, DR positive T cells as a reflection of actively involved cellular immunity within the CNS, while this accumulation of DR positive T cells is not seen in MS, a chronic inflammatory CNS disease, despite some of the patients being examined during clinical exacerbations.

Acute Disease↗