Biomedical subjects

R Jonsson

Publications and source records attributed to R Jonsson.

At least 37 records · Page 2Linked to original sources

PubMed2000

Isotype distribution of anti-Ro/SS-A and anti-La/SS-B antibodies in plasma and saliva of patients with Sjögren's syndrome.

In this study an ELISA assay was used to quantify the levels of antibodies against the recombinant Ro 52 kD, Ro 60 kD, and La 48 kD proteins in plasma and saliva of 17 Sjögren's syndrome patients. The levels of total IgG, IgA, and IgM were also quantified. About one third of the patients had salivary enrichment of IgA and IgM against the Ro 52 kD, Ro 60 kD, and La 48 kD antigens and IgG against La 48 kD, while no enrichment of IgG against Ro 52 kD and Ro 60 kD was found. Most correlations between plasma and saliva levels of antigen specific antibodies were highly significant, as were most correlations between focus score and levels of antigen specific antibodies in plasma and saliva. In total, the results support the hypothesis that autoantibodies are produced in the salivary glands. The strong correlation between focus score and plasma and saliva levels of autoantibodies, indicates that the local autoantibody production is a consequence of local inflammation.

Adult↗

PubMed2000

Monozygotic twins with primary Sjögren's syndrome.

Sjögren's syndrome (SS) is a chronic autoimmune disease mainly characterized by dry mouth and dry eyes due to an inflammatory process in the exocrine glands. We describe a pair of Caucasian monozygotic twin sisters and their mother, all having primary SS. The twins had very similar clinical presentation and almost identical serological data, and histological examination of lower labial salivary glands gave a focus score of 3 in both twins. We also present their family medical history, which shows aggregation of immunological disorders among family members, although the twins and their mother were the only individuals with primary SS.

Adult↗

PubMed2000

Fas and Fas ligand gene polymorphisms in primary Sjögren's syndrome.

OBJECTIVE: To screen for polymorphisms in the apoptosis regulating Fas and Fas ligand (FasL) genes in patients with primary Sjögren's syndrome (SS), and to explore associations with susceptibility to the disease. METHODS: Polymorphisms in Fas and FasL of 70 patients with primary SS and 72 controls were determined by polymerase chain reaction combined with the restriction enzyme fingerprinting single strand conformation polymorphism technique, verified by automatic sequencing and natural or amplification created restriction site tests. RESULTS: Polymorphisms were found in both Fas and FasL, but only some of the Fas polymorphisms were found in statistically significant differences between patients and controls. Patients displayed a higher frequency of the G/G genotype at position -671 than the controls, and the -671 G allele frequency for primary SS was increased compared to controls. A higher frequency of the C allele at position IVS2nt176 and IVS5nt82 was also found. Of note, the nucleotide variants in intron 2 and intron 5 were associated. CONCLUSION: We describe the positions and frequencies of several polymorphisms in the genes encoding Fas and FasL in patients with primary SS. None caused any amino acid change. Three Fas alleles, of which one is located in the promoter area, showed significant although modest differences between patients and controls.

Adult↗

PubMed1999

Immunoglobulin variable genes and epitope recognition of human monoclonal anti-Ro 52-kd in primary Sjögren's syndrome.

OBJECTIVE: To clone and characterize human anti-Ro/SSA autoantibodies from a patient with primary Sjögren's syndrome (pSS). METHODS: Monoclonal antibodies (mAb) were raised from the peripheral blood of a patient with pSS using Epstein-Barr virus transformation and a hybridoma technique. Specificity was determined using cell extracts, recombinant Ro 52-kd, Ro 60-kd, and La proteins as well as Ro 52-kd peptides in enzyme-linked immunosorbent assay (ELISA) and Western blot. The immunofluorescence pattern was analyzed using cultured human and mouse cell lines. Complementary DNA was amplified by polymerase chain reaction, and Ig variable (V)-region genes were directly sequenced. RESULTS: Two human anti-Ro 52-kd mAb of IgM isotype, denoted SG1 and SG3, were cloned from the peripheral blood of a patient with pSS. The 2 mAb reacted with the Ro 52-kd antigen in cell extracts of human cell lines and mouse cell lines, and with purified human recombinant Ro 52-kd protein in ELISA and Western blot. SG1 reacted specifically with 1 peptide, amino acids 136-156, of the Ro 52-kd protein, and SG3 was mapped to react with a recombinant fragment representing amino acids 136-292. Immunofluorescence studies revealed cytoplasmic staining with both mAb. Both were encoded by V(H)3-family genes. SG1 was highly homologous to the DP-77 germ-line gene, with 2 replacement mutations and 1 silent. It utilized the DPL-11 germ-line gene from the Vlambda2-family gene, with 1 silent mutation. SG3 was 100% homologous to the DP-47 germ-line gene, combined with a Vkappa1-family gene that was 100% homologous to the A30 germ-line gene. CONCLUSION: Two human mAb were demonstrated to be specific for the Ro 52-kd protein and to be directed against 2 different epitopes, 1 linear and 1 conformation-dependent, within a region previously described to be immunodominant. Somatic hypermutation appeared to be of minor importance in generating these 2 specificities.

Antibodies, Monoclonal↗

PubMed1999

Oral squamous cell carcinoma is associated with decreased bcl-2/bax expression ratio and increased apoptosis.

Expression of bcl-2 and bax and apoptosis were studied in fresh frozen samples of normal oral epithelium (OE, n = 7) and oral squamous cell carcinomas (OSCC, n = 16) by immunohistochemistry and the TUNEL method. In OE, bcl-2 was expressed in both basal (96.6% +/- 2.3% [mean +/- SD]) and suprabasal (91.8% +/- 6.2%) compartments. In OSCC, compared with OE, there was a marked reduction of bcl-2-positive cells in the basal part, and in the central parts of well-differentiated (33.0% +/- 19.7%, P < .001) and moderately differentiated (6.1% +/- 4.6%, P < .001) and also in poorly differentiated (1.9% +/- 0.2%, P < .001) tumors. More cells expressed bax in the suprabasal layer of OE (65.6% +/- 9.9%) and central parts of OSCC than in the basal layer of OE (19.1% +/- 4.1%) and basal parts of OSCC. A higher proportion of cells expressed bax in the central part of well-differentiated OSCC (74.3% +/- 8.2%) than in poorly differentiated OSCC (24.9% +/- 9.7%, P < .001). Apoptotic cell death was more pronounced in OSCC (1.5% +/- 0.9%) than in OE (0.4% +/- 0.1%, P < .05). We conclude that, in OSCC, compared with OE, there is a decreased bcl-2 expression, a lowered bcl-2/bax ratio and increased apoptosis. The expression of bax correlates with histological tumor grading in oral squamous cell carcinoma.

Antibody Specificity↗

PubMed1999

Elevated levels of human salivary epidermal growth factor after oral and juxtaoral surgery.

PURPOSE: Saliva provides a natural reservoir of growth factors whose purposes have remained elusive. Animal studies suggest that saliva-derived growth factors play a role in systemic and oral wound healing. In the current study, salivary concentrations of epidermal growth factor (EGF) were monitored in patients before and after oral and juxtaoral surgery. PATIENTS AND METHODS: Whole resting saliva was collected from a group of patients with parotid gland tumors requiring surgical resection. Another group of patients a history of periodontal disease requiring surgical intervention also provided whole salivary samples. Healthy age- and sex-matched persons served as controls. RESULTS: Salivary EGF levels were elevated in both groups of patients within 24 hours after surgery. In the periodontitis patients, a second smaller peak was assayed noted between 36 and 48 hours. After this, EGF concentrations returned to levels comparable to healthy controls in both experimental groups. CONCLUSIONS: Although the local cells have the ability to synthesize and secrete growth factors at a site of injury, these results suggest that surgery stimulates increased synthesis and secretion of growth factors in the saliva as well. This increased level of saliva-derived growth factor may also aid in promoting wound healing.

Adult↗

PubMed1999

Increased expression of Fas ligand on Mycobacterium tuberculosis infected macrophages: a potential novel mechanism of immune evasion by Mycobacterium tuberculosis?

We have studied the location and mechanism of apoptosis within the granulomas in the lungs at various stages of slowly progressive primary murine Mycobacterium tuberculosis infection. Parallel sections were analyzed for detection of mycobacterial antigens, Fas, and Fas ligand (FasL) by immunohistochemistry, and for apoptotic cells by terminal deoxynucleotidyl-transferase-mediated dUTP-digoxigenin nick end labeling (TUNEL) method. The frequency of apoptosis was high in the macrophage aggregates as compared to the lymphocyte aggregates and at the interface between them. Five to seven percent of the vacuolated macrophages in the granulomas expressed FasL intensely. These cells contained large amounts of mycobacterial antigens. These findings suggest that M. tuberculosis infection can induce increased expression of FasL in a population of infected macrophages. As a consequence the infected macrophages will be protected from the attack of cytotoxic T cells and activation of bactericidal mechanisms by Th1 type lymphocytes. This constitutes a novel evasion mechanism for M. tuberculosis possibly explaining the chronic course of infection.

Animals↗

PubMed1999

Ro/SS-A-reactive B lymphocytes in salivary glands and peripheral blood of patients with Sjögren's syndrome.

The aim of this study was to investigate the production of anti-Ro/SS-A antibodies in labial salivary glands (LSG) and peripheral blood (PB) of Sjögren's syndrome (SS) patients. The ELISPOT method was performed to quantify the frequency of LSG lymphocytes and PB lymphocytes spontaneously secreting anti-Ro/SS-A antibodies. The total number of IgG-, IgA- and IgM-producing cells was also quantified. The bovine Ro 60-kD protein was used as target antigen. Six of six primary SS patients had LSG B cells producing anti-bovine Ro 60 kD of the IgG isotype, and two of two primary SS patients had in addition PB lymphocytes producing anti-bovine Ro 60 kD of the IgG isotype. The six patients who had IgG antibodies against the Ro/SS-A antigen in LSG all had focus scores of >/= 7 in biopsies of LSG. The results indicate that SS patients with a high degree of local inflammation in LSG have B cells producing anti-Ro/SS-A antibodies in both LSG and PB. Thus, the anti-Ro/SS-A antibodies may have pathogenic importance in the progression of the exocrinopathy of SS.

Animals↗

PubMed1999

Ro/SS-A- and La/SS-B-reactive B lymphocytes in peripheral blood of patients with Sjögren's syndrome.

The aim of this study was to investigate the production of anti-Ro/SS-A and anti-La/SS-B antibodies in peripheral blood (PB) of patients with Sjögren's syndrome (SS). The ELISPOT method was performed to quantify the frequency of PB lymphocytes spontaneously secreting anti-Ro/SS-A and/or anti-La/SS-B antibodies. The total number of IgG-, IgA- and IgM-producing cells was also quantified. The recombinant Ro 52-kD, Ro 60-kD and La 48-kD proteins were used as target antigens. Three of 18 SS patients had PB lymphocytes secreting IgG antibodies against the recombinant Ro 52-kD protein. The same three patients had high serum titres of anti-Ro 52-kD antibodies. In addition, these patients were classified as having severe disease, and all three had focus scores of >/= 8 in biopsies of the labial salivary glands (LSG). The correlation between the number of PB cells producing IgG antibodies against the recombinant Ro 52-kD protein and the focus score was significant (P < 0.01). The results indicate that only SS patients with severe disease and high degree of local inflammation in LSG have B cells producing anti-Ro/SS-A antibodies in PB. Thus, most of the spontaneous autoantibody production must take place in other body compartments, e.g. in exocrine glands and probably also in the lymphoid organs and/or other mucosal sites.

Adult↗

PubMed1999

Rheumatoid factors in primary Sjögren's syndrome (pSS) use diverse VH region genes, the majority of which show no evidence of somatic hypermutation.

Rheumatoid factor (RF) is the most common autoantibody found in patients with Sjögren's syndrome (SS). To study the genetic origin and the mechanisms acting behind its generation we have characterized and sequenced the immunoglobulin VH genes used by 10 IgM RF MoAbs derived from peripheral blood of six female patients with pSS. We compared the structure of the RF immunoglobulin VH genes with those obtained previously from rheumatoid arthritis (RA) patients and healthy immunized donors (HID). VH1 and VH4 were each used by four RF clones, one clone was encoded by VH3 family gene and one by VH2 family gene. This distribution frequency was different from that observed in RA, where VH3 was the dominant family, followed by VH1. Eight different germ-line (GL) genes encoded the clones and all of these genes were seen previously in RA and/or HID RF. Five clones rearranged to JH6, four rearranged to JH4 and one to JH5, in contrast to RF from RA and HID, where JH4 was most frequently used. D segment use and CDR3 structure were diverse. Interestingly, three out of four VH4 clones used the GL gene DP-79 that was seen frequently in RA RF. The degree of somatic mutation in the pSS RF was very much lower than seen in RA and HID RF. All the pSS RF clones except three were in or very close to GL configuration. This indicates that there is little role for somatic hypermutation and a germinal centre reaction in the generation of RF from peripheral blood in pSS.

Adult↗

PubMed1999

An alternative perspective to the immune response in autoimmune exocrinopathy: induction of functional quiescence rather than destructive autoaggression.

Sjögren's syndrome is characterized by dryness of the eyes and the mouth due to mononuclear cell infiltration of the lacrimal and salivary glands. The aetiology is unknown but autoimmunity is considered to play a significant role in the pathogenesis. Recent studies have focused on the fact that tear and salivary flow involves an entire functional system that includes the mucosal surfaces with adnexes (the site of inflammation), efferent nerve signals sent to the midbrain (lacrimal and salivary response region), and afferent neural signals from the brain to the acinar/ductal epithelial structures in the gland. Mononuclear cell infiltration in exocrine glands can lead to glandular destruction, suggested to be mediated through apoptosis. However, the functional impairment of exocrine glands could be regulated by cytokines and/or antibodies against the muscarinic M3 receptor by inhibiting the neural stimulation of the residual glands. This review discusses the possibility that the pathogenesis of Sjögren's syndrome comprises aberrant immune-mediated neuro-hormonal events.

Animals↗

PubMed1999

Increased frequency of cells secreting interleukin-6 and interleukin-10 in peripheral blood of patients with primary Sjögren's syndrome.

Sjögren's syndrome (SS) is a chronic autoimmune disease of exocrine glands. There is increasing evidence that interferon-gamma (IFN-gamma) plays a role in the pathogenesis of SS. It has also been suggested that other type 1 cytokines, as well as interleukin-6 (IL-6), IL-10 and transforming growth factor-beta, are important in the induction and/or maintenance of SS. The aim of this study was to investigate the type 1/type 2 cytokine pattern in peripheral blood of primary SS patients. The enzyme-linked immunospot (ELISPOT) assay was performed to quantify the number of mononuclear cells (MNC) secreting IFN-gamma, IL-6 and IL-10 in peripheral blood samples from 33 patients with primary SS and 12 healthy controls. The mean number of cells secreting IFN-gamma was 9/105 MNC in the SS patient group, and 4/105 MNC in the control group (P = 0.73). Fifteen of the SS patients had anti-Ro 52 kDa antibodies in serum. In this patient group the mean number of cells secreting IFN-gamma was 4/105 MNC, while in the patient group without such antibodies the mean number of cells secreting IFN-gamma was 14/105 MNC (P = 0.04). The mean number of cells secreting IL-6 was 12 000/105 MNC in the SS patient group, and 5000/105 MNC in the control group (P = 0.01). The mean number of cells secreting IL-10 was 270/105 MNC in the SS patient group, and 180/105 MNC in the control group (P = 0.04). The SS patients had a significantly higher number of cells secreting IL-6 and IL-10 in peripheral blood than the healthy controls, which may facilitate B-cell activation and production of autoantibodies.

Adult↗

PubMed1999

Changes in T-lymphocyte subsets in lungs and spleens of mice with slowly progressive primary mycobacterium tuberculosis infection: involvement of unconventional T-cell subsets.

Our previous study showed that the cell-activation responses and cytokine-secretion patterns were different in lungs and spleens of mice with slowly progressive primary Mycobacterium tuberculosis infection. The aim of the present study was to characterize the T-cell subsets in lungs and spleens of mice with a similar infection. The percentages of T-cell subsets were determined by flow cytometry and the absolute numbers were calculated. Spleens of infected mice showed a threefold expansion of CD4+ cells but no change in CD8+ cells, whereas lungs had a threefold increase of both subsets. A significant expansion of CD4-CD8-alphabeta+ [double negative (DN)alphabeta+] subsets was observed in the lungs of infected mice compared with uninfected mice. This was not the case in the spleens of infected mice. In infected mice the CD4-CD8- (DN) population preferentially expressed alphabeta-T-cell receptors (TCR) in the lungs but gammadelta-TCR in the spleens. The percentages of many T-cell subsets were significantly higher in the lungs than in the spleens of both uninfected and infected mice. However, the percentages of CD4+ and CD4-CD8+TCR- subsets in the lungs were significantly lower than in the spleens of infected mice. We also observed some previously unreported T-cell subsets: double positive-TCR- (DPTCR-), DPalphabeta+ and DPgammadelta+. So far their functions are unknown.

Animals↗

PubMed1999

A mouse model for slowly progressive primary tuberculosis.

The progression from primary Mycobacterium tuberculosis infection to disease is usually slow in humans. The aim of this study was to develop and characterize a mouse model for slowly progressive primary tuberculosis, using the intraperitoneal (i.p.) route of infection, and to compare it with our previously described model of latent M. tuberculosis infection. B6D2F1 hybrid mice inoculated with 1.5 x 106 colony-forming units (CFUs) of M. tuberculosis H37Rv were followed-up for 70 weeks. Lungs, livers and spleens were examined for bacillary growth, histopathological changes and mycobacterial antigens (MPT64, ManLAM and multiple antigens of M. tuberculosis), by immunohistochemical staining. The infection was found to pass through three distinctive phases. During phase 1, mice were healthy despite development of small granulomas and an increasing number of bacilli in the lungs. During phase 2, mice were unwell but mortality was low. The count of M. tuberculosis and the granuloma size stabilized. The granulomas contained an increasing population of large, vacuolated macrophages. During phase 3, mice became moribund and died rapidly, but the M. tuberculosis count remained relatively stable. The inflammatory infiltrates filled approximately 80% of the lung parenchyma and the lesions were not well demarcated. Rapidly progressing inflammation, rather than an increase in the M. tuberculosis count, seems to contribute more to mortality.

Animals↗

PubMed1999

Improvement of subjective work performance among obstructive sleep apnea patients after treatment with continuous positive airway pressure.

Obstructive sleep apnea syndrome (OSAS) is a significant problem for some patients presenting with snoring and excessive daytime sleepiness. The 'golden standard' therapy in OSAS is considered to be nasal continuous positive airway pressure (CPAP). The effects of CPAP on work performance in sleep apnoics has not been studied previously. One hundred and fifty-two patients with OSAS participated in an open label study. The patients were diagnosed as suffering from severe OSAS after they underwent overnight polysomnography showing that their apnea indexes were at least 20. The participants answered four questions concerning self-perceived work performance prior to and after using CPAP during 6 months. There were highly statistically significant decreases (P < 0.000001) in work performance difficulties as graded by the patient. The results of this study indicate that CPAP treatment improves subjective work performance in patients suffering from OSAS.

Adult↗

PubMed1999

The influence of age on disease manifestations and serological characteristics in primary Sjögren's syndrome.

We have studied the influences of age on clinical manifestations and serological abnormalities in primary Sjögren's syndrome (pSS). The 67 patients included were diagnosed according to the preliminary European classification criteria for pSS, and disease manifestations were assessed according to a newly developed quantitative and qualitative classification model. We found that the age at diagnosis correlated to the presence of autoantibodies anti-SSA/SSB (r=-0.31, <0.02), rheumatoid factor (RF) (r=-0.33, p<0.01) and serum levels of IgG (r=-0.27, p<0.05). Young patients diagnosed before 45 years of age had the highest positivity of the autoantibodies anti-SSA/SSB (62.5%), RF (62.5%) and high levels of s-IgG (68.8%), while the corresponding values for old patients diagnosed after 60 years of age were anti-SSA/SSB: 20.8%, RF: 20.8%, and high s-IgG: 29.2%. None of these parameters correlated to age at onset nor disease duration. By applying a model for evaluating disease manifestations, no correlation between the global index nor the indices for subgroups of disease manifestations was found to age at onset, age at diagnosis, nor disease duration. We conclude that there is a significant influence of age on serological abnormalities in pSS, but not on disease manifestations.

Adult↗

PubMed1999

Suppression of Fas receptor and negative correlation of Fas ligand with differentiation and apoptosis in oral squamous cell carcinoma.

Apoptosis and the expression of Fas receptor (Fas) and Fas ligand (FasL) were studied in 8 samples of normal oral mucosa (OM) and in 19 oral squamous cell carcinomas (OSCC) by immunohistochemistry and the TUNEL method. Fas was detected in less than 2% of cells in OSCC compared with 84.3+/-9.0% of cells in the basal layer in OM. FasL was found to be highly expressed in poorly differentiated lesions (90.9+/-3.6%), and in cells of both the basal (88.3+/-4.3%) and central (85.3+/-5.7%) parts of moderately differentiated lesions, whereas in well-differentiated (WD) lesions expression was considerably lower in both basal (42.7+/-4.1%) and central (11.5+/-2.4%) parts. In normal OM FasL was primarily detected in cells of the basal layer, but in a high proportion of cells (84.9+/-4.3%). Apoptotic cell death was greater in OSCC (1.6+/-0.6%) than in OM (0.6+/-0.2%, P<0.05) and was most pronounced in the central part of WD OSCC (2.3+/-0.5%). Our results show that Fas is expressed in low quantities in OSCC and that FasL expression correlates negatively with degree of differentiation and apoptosis in OSCC.

Apoptosis↗

PubMed1999

Delayed recruitment of immunocompetent cells in denervated rat periodontal ligament following experimental tooth movement.

It has previously been shown that the number of mononuclear phagocytic cells in the periodontal ligament (PDL) of orthodontically moved rat molars is significantly increased (p < or = 0.05) at 3, 7, and 14 days compared with the controls. Since these changes coincide with increased density of peptidergic nerve fibers, it was of particular interest to investigate a possible relation between the immunocompetent cells and sensory nerve fibers in the PDL of experimentally moved and denervated rat molars. Twenty-two young animals had the first right mandibular molar moved mesially, 7, 14, and 21 days after ipsilateral inferior alveolar nerve axotomy. The left side served as unoperated control. An immunohistochemical procedure was carried out on alternate, serial, cryostat sections with antibodies against CDllb (macrophages, dendritic cells) and class II major histocompatibility complex (MHC) molecules (RT1B). At 7 and 14 days, the number of CD11b+- and RT1B-expressing cells in the denervated PDL showed no significant difference compared with the contralateral side. However, at 21 days, when periodontal tissue re-innervation is established, the number of the investigated immunocompetent cells in the PDL of the denervated and experimentally moved mandibular molars demonstrated a significant difference compared with the contralateral and control molars (p < or = 0.05). It can be concluded that axotomy of the inferior alveolar nerve delays the recruitment of macrophage-like and class II MHC molecule-expressing cells in the PDL of orthodontically moved rat molars. The results further indicate that sensory nerve fibers interact with immunocompetent cells and participate in their mobilization to locally inflamed tissues.

Animals↗