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Biomedical subjects

R Jonsson

Publications and source records attributed to R Jonsson.

At least 109 records · Page 6Linked to original sources

Spontaneous gingival antibody production to Fusobacterium nucleatum outer membrane in patients with adult periodontitis.

The local antibody response to Fusobacterium nucleatum outer membrane (FnOM) was analyzed in patients with adult periodontitis (AP) at the single cell level. Furthermore, we analyzed whether periodontal hygienic treatment could alter the antibody response. The number of IgG- and IgM-producing cells were investigated in gingival samples collected from 20 patients with AP. The patients were divided into 2 groups, before (BT, n = 9) and after (AT, n = 11) periodontal hygienic treatment. Four healthy gingival samples were used as controls. The results obtained showed that local antibody production against FnOM occurred in gingiva of patients with AP, but not in healthy gingiva. The IgG anti-FnOM was the predominant isotype observed. However, there was no statistically significant difference between the BT and AT groups. These results indicate that periodontal hygienic treatment was not sufficient to alter significantly the number of IgG- and IgM-secreting cells present in gingival tissue of AP patients, but it promoted a reduction of IgG anti-FnOM secreting cells. The presence of anti-FnOM antibodies in AP but not in control patients indicates that this bacteria may play a role in the pathogenesis of periodontal disease.

Antibodies, Bacterial↗

Effects of calprotectin in avridine-induced arthritis.

Plasma levels of calprotectin correlate with disease activity and clinical assessments of arthritis in various rheumatic diseases, and high levels have been demonstrated in the synovial fluid of patients with rheumatoid arthritis. However, the role of calprotectin in rheumatic inflammation is unclear. The purpose of the present study was to investigate potential intra-articular effects of calprotectin. Calprotectin was injected into joints of healthy male Lewis rats and into joints of rats in the latency period before onset of avridine-induced arthritis. In addition, a group of animals had IgG antibodies to rat calprotectin injected into joints before onset of avridine-induced arthritis. Injection of 0.2 or 10 micrograms calprotectin into the ankles of healthy male Lewis rats resulted in histologically minor and reversible inflammatory changes, but without any circulating antibodies to calprotectin. Furthermore, animals with 40 micrograms calprotectin injected into ankles before the expected onset of avridine-induced arthritis had lower scores for cellular infiltration than were seen in control joints. This difference did not quite reach statistical significance in the two-sided test used. However, the induced arthritis increased in joints injected with IgG antibodies to calprotectin. These findings may indicate that increased local concentrations of calprotectin are partially protective against avridine-induced arthritis. In contrast, reduced local concentrations appear to exacerbate the severity of arthritis. Calprotectin may thus be involved in the regulation of inflammatory processes in joints.

Adjuvants, Immunologic↗

Recruitment of immunocompetent cells after dentinal injuries in innervated and denervated young rat molars: an immunohistochemical study.

The dental pulp represents a peripheral end-organ deprived of a collateral nerve supply. After inferior alveolar nerve (IAN) axotomy, rat molar pulp is denervated over a period of at least 6 days. Therefore, rat molar pulp was used as an experimental model to study the effect of sensory nerve fibers on influx of immunocompetent cells after dentinal injury. In the present study we performed a quantitative analysis of CD43+, CD4+, CD11b+, and I-A antigen-expressing cells subjacent to dentinal cavities in denervated and innervated first mandibular molars. For visualization of nerve fibers, antibodies to protein gene product (PGP) 9.5, the sensory neuropeptides substance P (SP) and calcitonin gene-related peptide (CGRP), and the sympathetic neuropeptide Y (NPY) were used. Immunohistochemistry was performed by the avidin-biotin-peroxidase method. In the innervated teeth, a correlation between increased sensory nerve density and influx of immunocompetent cells was found. Compared to the contralateral innervated molars, a significant reduction in recruitment of immunocompetent cells was found in the denervated pulp tissue subjacent to the dentinal cavities. The rat molar represents a unique model to illustrate the influence of sensory nerves and neuropeptides on inflammation and recruitment of immunocompetent cells.

Animals↗

Characterization of T cell receptor repertoire and anti-Ro/SSA autoantibodies in relation to sialadenitis of NOD mice.

Non-obese diabetic (NOD) mice develop sialadenitis which morphologically resembles the exocrinopathy in human Sjögren's syndrome (SS). The sialadenitis is characterized by focal infiltrates of inflammatory cells. Immunoenzyme staining (ABC-technique) and monoclonal antibodies defining CD4, CD8, CD11b, TCR alpha/beta, gamma/delta, V beta 2, V beta 4, V beta 6, V beta 7, V beta 8.1, 2, V beta 10b and V beta 11 were used to examine the infiltrating mononuclear cells (MNC) in salivary glands of NOD mice. TCR alpha beta + cells dominated clearly over TCR gamma delta + cells in the salivary glands. A predominance of CD4+ T-cells was identified, while a small population of CD8+ cells was found in the salivary gland infiltrates. CD11b+ mononuclear cells were sporadically seen within the salivary gland lesions. All different TCR V beta:s which were analysed appeared to be utilized at the site of MNC infiltration in salivary glands; although with various frequencies. The frequency pattern of V beta gene expression in salivary glands was V beta 8.1,2 (15%) > V beta 6 (12%) > V beta 4 (11%) > V beta 10b (5%) > V beta 11 (5%) = V beta 2 (5%) > V beta 7 (3%). Analysis of the TCR V beta utilization in corresponding lymph nodes revealed a quite similar frequency pattern as found in the salivary glands. Serum samples were also tested for anti-Ro52, Ro60 and anti-La antibodies with Western blot. Autoantibody production was limited to anti-Ro/SSA and 3/37 (8%) of the mice were found to produce anti-Ro52 kD antibodies. The degree of sialadenitis (focus score) appeared not to influence reactivity to the Ro52 kD protein.

Animals↗

Analysis of T-cell receptor expressing lymphocytes infiltrating squamous cell carcinomas of the upper aerodigestive tract.

T-lymphocytes expressing T-cell receptors (TCRs) of the gamma/delta type have been suggested to play an important role in mucosal defense against infection and neoplastic transformation. In this study, an immunohistochemical investigation was performed on the distribution of alpha/beta and gamma/delta TCRs among tumor-infiltrating lymphocytes. Thirteen patients with squamous cell carcinomas of the upper aerodigestive tract were studied, using monoclonal antibodies and an avidin-biotin-peroxidase technique. Most of the T-cells had an alpha/beta TCR. Only 1.6% of the T-cells within the cancer tissue and 1.2% of the T-cells in the parenchyma adjacent to the cancer tissue expressed gamma/delta TCRs. These results are consistent with the results of similar studies in bronchial and breast carcinomas. Biopsies from normal oral mucosa in nine healthy individuals showed that 1.3% of the T-cells within the epithelium and 1.0% of those in the lamina propria adjacent to the epithelium expressed gamma/delta TCRs. Quantitatively the results do not support the theory that gamma/delta T-cells play an important role in the immunological response against cancer tissue in the mucosa of the upper aerodigestive tract. The functional role of these cells in the mucosa and in response to carcinomas is, however, still uncertain.

Adult↗

Effects of human calprotectin (L1) on in vitro immunoglobulin synthesis.

Calprotectin (L1) is a major cytoplasmic protein of neutrophilic granulocytes and monocytes/macrophages which is released from leucocytes during activation or cell death. Apart from in vitro antimicrobial and antiproliferative activity little is known about the biological function of the protein. Since previous investigations have shown that calprotectin plasma levels are elevated in various inflammatory rheumatic diseases, we wanted to investigate if calprotectin has an effect on immune cell functions. Peripheral blood mononuclear cells, either unstimulated or polyclonally stimulated with mitogen, were incubated with calprotectin and effects were assessed by enumeration of immunoglobulin secreting cells (ELISPOT). The results indicate that incubation with high concentrations of calprotectin (> 64 micrograms/ml) inhibit the production of the three classes of immunoglobulins investigated (IgG, IgM and IgA), both for mitogen stimulated and unstimulated lymphocytes. Except for the highest concentration of calprotectin (500 micrograms/ml), it seems plausible that the observed inhibitory effect of calprotectin on Ig production is not a result of a direct toxic effect of calprotection on B lymphocytes. Altogether, these effects of high calprotectin levels might be of importance in the immunoregulation of inflammatory conditions.

Adult↗

Some microbiological, histopathological and immunohistochemical characteristics of progressive periodontal disease.

The aim of the present investigation was to study the local nature of human periodontal disease by assessing the microbiota and the composition of the tissue lesions at sites with progressive attachment loss in periodontitis susceptible subjects. 300 subjects with periodontal disease were monitored for 2 years without treatment. 8 subjects lost > 2 mm of attachment at > or = 3 sites during both the first and the second 12 month interval. These 8 subjects (progressive disease group; PD) were recalled for a microbiological and histopathological examination. A group of age- and sex-matched subjects were identified who during the 2 years of monitoring exhibited gingivitis and deep pockets, but no further attachment loss. This group of 11 subjects (non-progressive disease group; NPD) served as controls. From the 8 active disease subjects, > or = 1 interproximal site which had displayed disease activity (progressive disease active; PDA) and > or = 1 contralateral site without disease progression (progressive disease inactive; PDI) were sampled. From the 11 control subjects, 1 site/subject was sampled (NPD). The total number of viable micro-organisms (TVC) in the subgingival microbiota was estimated and a series of bacterial species were identified and enumerated. The gingival tissue of the sampling site was excised and the soft tissue prepared for morphometrical and immunohistochemical analyses. No differences were observed in the subgingival microbiota of the sample sites in the subjects who exhibited disease progression (PD) when compared with the subjects with periodontally diseased but stable conditions (NPD).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Sjögren's syndrome in inflammatory rheumatic diseases: analysis of the leukocyte protein calprotectin in plasma and saliva.

In a hospital population of 154 patients with a wide range of inflammatory rheumatic diseases, patients with sicca symptoms were subjected to objective ocular and oral tests to establish cases with Sjögren's syndrome (SS). The plasma level of the leukocyte protein calprotectin has been shown to be a good indicator of disease activity and inflammation in various rheumatic diseases. In the present study, calprotectin levels in plasma and whole saliva were analysed and evaluated as potential markers of SS and salivary gland disease activity. Plasma calprotectin levels did not differ significantly between patients with SS and patients with no sicca symptoms. However, salivary calprotectin levels correlated significantly with the plasma calprotectin levels and with several ocular variables, weakly with salivary flow and serum rheumatoid factor, but not with focal sialadenitis. In conclusion, this study shows that salivary calprotectin levels seem to be associated with several variables of SS glandular pathology, indicating the need for further and more comprehensive studies on calprotectin in various oral fluids and in lacrimal fluid in relation to SS glandular disease activity.

Blood↗

MRL/lpr mice produce anti-Ro 52,000 MW antibodies: detection, analysis of specificity and site of production.

MRL/lpr mice are studied as one of the animal models of the human autoimmune disease Sjögren's syndrome. The mice develop inflammatory exocrinopathy resembling that of patients with Sjögren's syndrome. To investigate if MRL/lpr mice produce the anti-Ro/SS-A and anti-La/SS-B autoantibodies common to Sjögren's syndrome patients, mouse sera were tested in ELISA and Western blot with recombinant Ro 60,000 MW, Ro 52,000 MW and La antigen. Thirty per cent of mice aged 4 months and 5% of mice aged 2 months produced antibodies to human Ro 52,000 MW. Antibodies to Ro 60,000 MW and La were found in a low percentage of the older mice but not at all in the younger mice. Immunohistological staining of mouse organ sections demonstrated anti-Ro 52,000 MW-producing cells in spleen, lymph nodes and salivary glands of seropositive animals. These findings provide further evidence for the usefulness of the MRL/lpr mouse as a model for Sjögren's syndrome.

Animals↗

Measurement of plasma calprotectin as an indicator of arthritis and disease activity in patients with inflammatory rheumatic diseases.

OBJECTIVE: To investigate if the plasma level of the granulocyte protein calprotectin is a useful indicator of severity of arthritis in patients with inflammatory rheumatic diseases, and to analyze which factors contribute to the raised plasma calprotectin levels. METHODS: Plasma calprotectin levels were measured by ELISA: In a cross sectional study of 154 patients with various inflammatory rheumatic diseases, calprotectin levels were correlated with laboratory and clinical variables. RESULTS: The plasma levels of calprotectin and C-reactive protein (CRP) correlated significantly with the clinical evaluation of swollen joints (r = 0.51, p < or = 0.01 and r = 0.29, p < or = 0.01, respectively). Calprotectin levels, but not CRP levels or erythrocyte sedimentation rate, were significantly lower in patients with no swollen joints than in patients with one or more swollen joints (2613.6 micrograms/l vs 6287.0 micrograms/l, p < 0.001). A significant correlation between calprotectin and number of neutrophils was demonstrated (r = 0.43, p < or = 0.01), indicating that circulating neutrophils contribute to plasma calprotectin levels. CONCLUSION: The plasma calprotectin level may be a useful indicator of arthritis in inflammatory rheumatic diseases.

Adolescent↗

Oligoclonality of T cells in salivary glands of autoimmune MRL/lpr mice.

The aim of this study was to obtain further information about exocrine glandular immunopathology and the potential of the MRL/lpr strain as a model of Sjögren's syndrome. Immunoenzyme staining (ABC technique) and monoclonal antibodies defining CD3 T-cell receptor (TcR) alpha beta, gamma delta and TcR V beta 2, V beta 4, V beta 6, V beta 7, V beta 8.1,2, V beta 10b and V beta 11 were used to identify the mononuclear cells (MNC) in salivary gland infiltrates and lymph nodes of 2- and 4-5-month-old female MRL/lpr mice. TcR alpha beta + cells dominated clearly over TcR gamma delta + cells in both salivary glands and lymph nodes. In addition, to be expressed on lymphocyte-like cells, TcR gamma delta + cells also had a dendritic appearance. The frequency pattern of TcR expression in early inflammation (2 months) was V beta 8.1, 2 > V beta 6 > V beta 4 > V beta 10b > V beta 2 > V beta 7 > V beta 11. Clear differences in frequencies could be found between salivary glands and lymph nodes in established sialadenitis (4-5 months). Particularly V beta 4, V beta 8.1,2 and V beta 10b showed expansion in salivary glands at > or = 4 months. In conclusion, this study shows a diverse repertoire of TcR at local sites of MNC infiltration in autoimmune MRL/lpr mice. However, with increasing age it also shows a preferential utilization of certain V beta gene products.

Animals↗

Progression of sialadenitis in Sjögren's syndrome.

An analysis of progression of sialadenitis in patients with primary and secondary SS has been performed. For this purpose patients were prospectively followed and evaluated with respect to stimulated whole salivary secretion and morphology of labial salivary gland biopsies. Twenty-one patients with primary SS and 18 with secondary SS were followed for a mean of 39 +/- 20 months (range 11-112 months). During this observation period the lymphocytic infiltration in minor salivary glands, measured as focus score, increased in 14/21 (67%) patients with primary SS and in 14/18 (78%) patients with secondary SS. Altogether there was a statistically significant increase in focus score in both primary and secondary SS, but no reduction in salivary production. Consequently, no correlation between changes in focus score and stimulated salivary secretion was found in either primary or secondary SS.

Adult↗

Estrogen accelerates immune complex glomerulonephritis but ameliorates T cell-mediated vasculitis and sialadenitis in autoimmune MRL lpr/lpr mice.

Estrogen is known to influence immune responses in healthy subjects in a dichotomous fashion. Thus, in number of previous studies we and others have demonstrated that B cell activities are augmented after exposure to estrogen whereas T cell reactivity is suppressed. Furthermore, it has been shown that this hormone has significant impact on the course of certain human and experimental autoimmune diseases. In this study we report that treatment with physiological doses of estradiol exerts dichotomous effects on different manifestations of the lupus disease in MRL/l mice. On one hand immune complex-mediated glomerulonephritis was significantly accelerated. This outcome was due to polyclonal B cell activation with increased production of antibodies to double-stranded DNA and formation of circulating immune complexes. In contrast, T cell-mediated lesions such as focal sialadenitis, renal vasculitis, and periarticular inflammation were all significantly ameliorated in MRL/l mice exposed to estrogen. Thus, we were able to demonstrate that, within one subject and even within one organ, administration of estrogen leads to differential outcome of SLE morbidity. We propose that the differential effect of estrogen on the manifestations of the autoimmune disease of MRL/l mice is due to its dichotomous effects on B and T cell-mediated immune responses.

Animals↗

Genetic, hormonal and behavioural influence on spontaneously developing arthritis in normal mice.

DBA/1 male mice develop arthritis spontaneously at the age of 4 months. The affected joints show cell-rich pannus formation without T cell infiltration and only limited MHC class II expression. Specific pathogen-free DBA/1 mice from different sources developed the same disease. Analyses of inbred mouse strains with various genetic backgrounds and F1 hybrids revealed that the disease is genetically dependent of DBA/1 recessive genes. However, F1 hybrids between DBA/1 and BXSB spontaneously developed arthritis with earlier onset than DBA/1 mice, suggesting that the BXSB autoimmune gene background had both permissive and contributing effects on the development of arthritis. The complete male preponderance for disease susceptibility was investigated by castration and testosterone treatment of DBA/1 males. No arthritis developed after castration and disease susceptibility was restored by testosterone treatment. Arthritis developed only where more than two males were kept in cages, suggesting an influence by aggressive behaviour. Thus, the spontaneous development of arthritis is dependent on hormonal and behavioural mediated effects and differs from experimental models for rheumatoid arthritis such as type II collagen-induced arthritis and pristane-induced arthritis. We conclude that the spontaneously developing arthritis in the normal DBA/1 strain may be more useful as a disease model for osteoarthritis than for rheumatoid arthritis.

Animals↗

Arthritis induced in rats with adjuvant oil is a genetically restricted, alpha beta T-cell dependent autoimmune disease.

Adjuvant arthritis in rats is usually induced by injection of mycobacterium tubercle cell walls suspended in various adjuvant oils such as Freund's incomplete adjuvant (FIA) or pristane. We have recently shown that injection of adjuvant oils without inclusion of mycobacterium tubercle cell walls triggers arthritis [oil adjuvant-induced arthritis (OIA)] in the DA rat strain. The OIA is a genetically restricted disease since only DA rats are susceptible while Lewis, DA-fostered Lewis and F1 (Lew x DA) rats are relatively resistant. Activated alpha beta T cells infiltrate the affected joints of adjuvant oil-injected DA rats and treatment with monoclonal antibodies to the alpha beta T-cell receptor abrogates development of arthritis. These findings show that alpha beta T-cell activation is a critical event in the development of OIA.

Animals↗