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Biomedical subjects

C G Kallenberg

Publications and source records attributed to C G Kallenberg.

At least 127 records · Page 7Linked to original sources
PubMed1994

Serial nailfold capillary microscopy in primary Raynaud's phenomenon and scleroderma.

Eighty-four patients with long-standing Raynaud's phenomenon (RP) were evaluated by nailfold capillary microscopy (NCM) in a cross-sectional and longitudinal study. The patients were classified in five diagnostic groups: primary familial RP (n = 16), primary nonfamilial RP (n = 20), possible scleroderma (n = 27), scleroderma (n = 16), and the CREST (calcinosis, Raynaud's phenomenon, esophageal dysmotility, sclerodactyly, and telangiectasia) syndrome (n = 8). In the cross-sectional study, NCM showed gradually decreasing numbers of capillary loops and increasing numbers of widened and giant loops in the following order: primary RP, possible scleroderma, and scleroderma/CREST, suggesting that these diseases are part of a continuing spectrum of RP. In the longitudinal study there was a decrease in the total number of nailfold capillary loops in scleroderma/CREST but not in primary RP and possible scleroderma.

Adult↗
PubMed1994

Host-microflora interaction in systemic lupus erythematosus (SLE): colonization resistance of the indigenous bacteria of the intestinal tract.

Experimental data suggest a role for the microflora in Systemic Lupus Erythematosus (SLE). Anti-ds-DNA antibodies may be pathogenic in SLE by forming immune complexes with DNA. Foreign bacteria in the intestines could constitute the stimulus for anti-ds-DNA antibody production in SLE. Colonization Resistance (CR) is the defence capacity of the indigenous microflora against colonization of the intestines by foreign bacteria. A low CR implies increase of translocation of bacteria and a higher chance of subsequent, possibly DNA-cross-reacting antibacterial antibody production. We measured CR by a comprehensive biotyping technique in healthy individuals and patients with inactive and active SLE. CR tended to be lower in active SLE patients than in healthy individuals (P = 0.09, Wilcoxon one sided, with correction for ties). This could indicate that in SLE more and different bacteria translocate across the gut wall due to a lower CR. Some of these may serve as polyclonal B cell activators or as antigens cross-reacting with DNA.

Acute Disease↗
PubMed1994

Neutrophil activation in vitro and in vivo in Wegener's granulomatosis.

The mechanisms underlying glomerular capillary wall injury in Wegener's granulomatosis (WG) are not well understood. Anti-neutrophil cytoplasmic antibodies (ANCA), present in sera from patients with WG, are known to stimulate respiratory burst and degranulation of primed polymorphonuclear neutrophils (PMN) in vitro. Experimental studies have shown that oxygen radical production and lysosomal enzymes are important mediators of glomerular capillary wall injury. In the present study we investigated the presence of activated PMN and the extracellular localization of lysosomal enzymes in 28 consecutive renal biopsies from patients with WG. The presence of activated PMN within the renal biopsies was compared with the capacity of ANCA, isolated from simultaneously drawn serum samples, to activate primed PMN obtained from a normal donor. Both parameters were also related to renal function. Renal biopsies were obtained from newly diagnosed WG patients before therapy had started. Activation of PMN in the biopsies was assessed by measuring hydrogen peroxide production in situ. The number of activated PMN in the biopsy correlated with the extent of impairment of renal function. Proteinase 3, myeloperoxidase, and elastase, all targets of ANCA, were localized extracellularly in renal tissue and were also found within tubular epithelial cells. All ANCA positive samples were capable of activating primed PMN. The amount of activation correlated with the ANCA titer in those samples. No correlation, however, was found between the in vitro capacity of ANCA-positive IgG fractions to activate primed PMN and the number of activated PMN present in the renal biopsy. We conclude that activated PMN producing toxic oxygen metabolites and releasing lysosomal enzymes, are present in renal biopsies from patients with WG. The amount of activated PMN present within the kidney, and not the capacity of the corresponding ANCA to activate PMN, correlates with renal tissue damage as assessed by serum creatinine levels.

Antibodies, Antineutrophil Cytoplasmic↗
PubMed1994

Long-term follow-up of 46 patients with anti-(U1)snRNP antibodies.

The records of 46 patients with anti-(U1)snRNP antibodies and a minimal period of follow-up after first clinical presentation of at least 5 yr were examined with emphasis on symptoms contributing to established criteria of SLE, systemic sclerosis (SSc), RA or dermato- or polymyositis (DM/PM). At first clinical presentation 13 (28%) of the 46 patients studied fulfilled ARA-criteria for SLE (n = 10), RA (n = 2) and SSc (n = 1), and 33 (72%) were classified as mixed connective tissue disease (MCTD). During follow-up 18 patients initially classified as MCTD were now classified as SLE (n = 5), SSc (n = 7), RA (n = 3), or a combination of these disorders (n = 3). A transformation of MCTD towards these connective tissue diseases occurred 2.6 +/- 3 yr (mean +/- S.D.) after first clinical presentation. At the end of the follow-up period 67% of the patients fulfilled ARA criteria for SLE, SSc, RA or a combination of these diseases. The majority of patients with anti-(U1)snRNP antibodies have or will develop a classified connective tissue disease within 5 yr after clinical presentation. This undermines the concept of MCTD being a distinct clinical entity.

Adult↗
PubMed1994

Arteritis of both carotid arteries in a patient with focal, crescentic glomerulonephritis and anti-neutrophil cytoplasmic autoantibodies.

We report a 32-yr-old woman who suffered a stroke as a consequence of arteritis of both internal carotid arteries confirmed by selective carotid arteriography. Laryngeal inflammation and kidney biopsy proven focal crescentic glomerulonephritis were also present in this patient. Anti-neutrophil cytoplasmic autoantibodies with specificity for proteinase 3 were detected in high titre during the active phase of the disease. This overlap syndrome with features indicating both Takayasu's arteritis and Wegener's granulomatosis suggests a common pathogenesis for these diseases.

Adult↗
PubMed1994

Overlapping syndromes, undifferentiated connective tissue disease, and other fibrosing conditions.

Mixed connective disease is the prototype of an overlapping connective tissue disease. Based on the presence of a specific autoantibody directed against U1-snRNP (U1 small ribonucleoprotein), the syndrome has been considered a distinct disease entity. Patients with anti-U1-snRNP antibodies, however, do not present with a homogeneous clinical syndrome, and the majority develop a classified connective tissue disease within 5 years of presentation. Signs of scleroderma predominate in most patients. The immune response resulting in anti-U1-snRNP seems antigen driven and may result from molecular mimicry between U1-snRNP and certain viral proteins. Fibrotic conditions related to extrinsic factors have been described as human adjuvant disease. Case reports suggest that Swanson silastic joint prostheses can induce granulomatous reactions at a distance from the joints due to leaking of silicone from the implants. Much attention recently has been given to the possible induction of scleroderma-like syndromes in relation to silicone gel breast implants. However, the presently available data do not show convincing evidence that women with silicone gel breast implants are significantly at risk for developing a connective tissue disease.

Breast Implants↗
PubMed1994

T cell reactivity to proteinase 3 and myeloperoxidase in patients with Wegener's granulomatosis (WG).

T cell-mediated immunity is hypothesized to play an important role in the pathogenesis of granulomatous inflammation and vasculitis as found in patients with WG. The antigenic specificities of those T cells remain, however, unknown. Anti-neutrophil cytoplasmic antibodies (ANCA) present in patients with WG are directed to proteinase 3 (PR3) and myeloperoxidase (MPO). In the present study we investigated the proliferative capacity of peripheral blood mononuclear cells (PBMC) from patients with WG and age- and sex-matched controls in response to the WG autoantigens PR3 and MPO. Possible mitogenic effects of active PR3 and toxic effects of active MPO were excluded by using heat-inactivated PR3 and MPO. Antigen-specific stimulation induced by these autoantigens was studied by using processed PR3 and MPO in the lymphocyte stimulation test (LST). Proliferation induced by processed antigen correlated with that by heat-inactivated free antigen. The general capacity to proliferate in response to mitogens and recall antigens did not differ between patients and controls. However, patients with WG who were or had been positive for PR3-ANCA (n = 17) responded more strongly to PR3 than to MPO and showed higher responses to PR3 compared with controls (n = 13). Within the PR3-ANCA group T cell proliferation did not correlate with ANCA titre. In a small group of patients with MPO-ANCA (n = 5) no differences were observed compared with controls for MPO-specific proliferation. The data presented demonstrate that autoreactive PR3-specific T cells are present in patients with WG. Their fine specificity and possible role in the pathogenesis of WG have to be defined in further studies.

Adult↗
PubMed1994

Levels of soluble VCAM-1, soluble ICAM-1, and soluble E-selectin during disease exacerbations in patients with systemic lupus erythematosus (SLE); a long term prospective study.

Active SLE is characterized by immune deposits and subsequent vascular inflammation in many organs. Expression and up-regulation of adhesion molecules is basic to migration of inflammatory cells into the tissues. Recently, soluble isoforms of these molecules have been described which might be an expression of their up-regulation in the tissues and, as such, of disease activity. The purpose of this study was to evaluate whether changes in levels of soluble adhesion molecules reflect disease activity. We analysed serial sera in a 6-month period preceding 22 consecutive exacerbations of SLE for levels of soluble vascular cell adhesion molecule-1 (sVCAM-1), soluble intercellular adhesion molecule-1 (sICAM-1), and sE-selectin. Levels were related to clinical disease activity (SLEDAI), and levels of anti-dsDNA and complement. At the time of maximal disease activity, levels of sVCAM-1 in patients with SLE were higher than those in controls (P < 0.0001), levels in patients with renal involvement being higher than in those without (P < 0.02). Levels of sVCAM-1 correlated with SLEDAI scores (P < 0.05) and, inversely, with levels of C3 (P = 0.01). In addition, in the presence of anti-dsDNA, levels of sVCAM-1 tended to correlate with levels of these autoantibodies (P < 0.1). Levels of sICAM-1 were normal and sE-selectin levels even decreased compared with controls. Levels of sVCAM-1 were higher at the moment of relapse (P = 0.001) than at 6 months before this time point. This rise correlated with the rise in SLEDAI score (P < 0.02). Levels of sICAM-1 and sE-selectin did not rise, and remained in the normal range in all exacerbations studied. In conclusion, in contrast to sICAM-1 and sE-selectin, levels of sVCAM-1 are increased, rise parallel to disease activity during exacerbations in SLE, and are associated with decreasing levels of complement factors. This favours the hypothesis of immune deposit formation, activation of the complement cascade and activation of endothelial cells. Concurrent up-regulation of vascular adhesion molecules may thus result in transmigration of activated inflammatory cells inducing tissue damage.

Adult↗
PubMed1994

Activation of granulocytes by anti-neutrophil cytoplasmic antibodies (ANCA): a Fc gamma RII-dependent process.

ANCA have been demonstrated to induce the respiratory burst in primed neutrophils. In this study we have extended the investigations on neutrophil activation by ANCA directed against proteinase 3 (PR3), myeloperoxidase (MPO) and lactoferrin (LF), and we have analysed the underlying mechanisms. All three ANCA antigens were expressed on the cell surface of primed neutrophils. Superoxide production assayed by both cytochrome c reduction and oxidation of dihydrorhodamine 123, was induced by heterologous polyclonal anti-MPO and anti-LF antibodies, and ANCA-positive plasma samples. Induction of superoxide production was dose-dependent. F(ab')2 fragments did not induce the respiratory burst. Blockade of Fc receptors by specific MoAbs showed that anti-Fc gamma RII antibodies were able to turn off the ANCA-induced respiratory burst, whereas anti-Fc gamma RIII antibodies did not. Plasma samples that induced the respiratory burst did not differ from samples that did not induce superoxide production with respect to ANCA titre, but had higher levels of the IgG3 subclass of ANCA. Levels of the other subclasses of ANCA were comparable between those samples. We conclude that ANCA-induced activation of primed neutrophils is Fc gamma RII-dependent, and appears to be facilitated by antibodies of the IgG3 subclass.

Antibodies, Antineutrophil Cytoplasmic↗
PubMed1994

Podocyte expression of MHC class I and II and intercellular adhesion molecule-1 (ICAM-1) in experimental pauci-immune crescentic glomerulonephritis.

We examined immunopathological changes of podocytes in vivo which, based on in vitro studies, are thought to be relevant for the pathogenesis of renal diseases. We investigated the alterations of podocytes in local inflammation in a recently developed model of pauci-immune necrotizing crescentic glomerulonephritis (NCGN) in the rat. Frozen and plastic embedded kidney sections at different time points of the disease were incubated with antibodies directed to MHC class I, MHC class II, ICAM-1 and to relevant cytokines. Strong glomerular expression of MHC class I, II and ICAM-1 was found within 4 days, and plastic embedded sections clearly demonstrated increased cell membrane staining of podocytes. Increased glomerular interferon-gamma (IFN-gamma) was detected within 24 h of induction of NCGN, and IL-1 beta and tumour necrosis factor-alpha (TNF-alpha) were found from day 4. The potency of these cytokines to induce adhesion molecules on podocytes was investigated on rat glomerular epithelial cells in vitro. By using FACS analysis and electron microscopical techniques, we found that the in vivo expression of MHC class I, II and ICAM-1 by podocytes could in vitro be simulated by IFN-gamma. IFN-alpha weakly induced MHC class I, while IL-1 beta and TNF-alpha were ineffective. We hypothesize that podocytes in this in vivo model are important to maintain the local inflammatory process in the glomerulus by expression of relevant adhesion molecules and MHC molecules upon stimulation with specific cytokines.

Animals↗
PubMed1994

Anti-neutrophil cytoplasmic antibodies (ANCA) in inflammatory bowel disease: characterization and clinical correlates.

ANCA were detected by indirect immunofluorescence in 34 out of 67 patients with ulcerative colitis (UC, 51%) and in 14 out of 35 patients with Crohn's disease (CD, 40%). All but one ANCA-positive sera produced a perinuclear pattern of fluorescence (P-ANCA) on ethanol-fixed neutrophils. On paraformaldehyde-fixed neutrophils 76% of P-ANCA-positive sera in UC and 50% of P-ANCA-positive sera in CD produced cytoplasmic fluorescence, indicating that, indeed, cytoplasmic antigens are recognized by a considerable number of these sera. By Western blot analysis using whole neutrophil extract as a substrate 46% of sera from patients with UC and 32% of sera from patients with CD showed reactivity with either lactoferrin, polypeptides occurring as a doublet of 66/67 kD mol. wt, or polypeptides occurring as a doublet of 63/54 kD mol. wt, respectively. Identical patterns of reactivity have been observed among P-ANCA-positive sera from patients with autoimmune liver disease and rheumatoid arthritis. These data suggest that ANCA of restricted specificities are not specific for inflammatory bowel disease (IBD), but are present in diverse conditions characterized by chronic idiopathic inflammation.

Adolescent↗
PubMed1994

Changes in levels of soluble T-cell activation markers, sIL-2R, sCD4 and sCD8, in relation to disease exacerbations in patients with systemic lupus erythematosus: a prospective study.

OBJECTIVES: To assess serial activation of T-cell subsets in relation to auto-antibody production and the occurrence of disease exacerbations in patients with systemic lupus erythematosus (SLE). METHODS: To study the possible role of T-cells in the pathophysiology of the disease, 16 consecutive exacerbations were prospectively studied in a cohort of patients with SLE, and serial plasma levels of sIL-2R, sCD4, and sCD8 preceding and during these exacerbations were determined. Levels of these molecules were related to total IgM and IgG, and anti-dsDNA. RESULTS: During major disease exacerbations (n = 6), levels of sIL-2R increased significantly (p < 0.001). Levels of sCD4 were predominantly in the normal range, whereas levels of sCD8 were frequently increased. No change in levels of both molecules could be detected in the period before the exacerbation. During minor exacerbations (n = 10), levels of sIL-2R remained stable. Levels of sCD4, however, tended to drop, whereas levels of sCD8 tended to rise. No correlations were found between sIL-2R, sCD4 or sCD8 on the one hand, and total IgM, IgG, or anti-dsDNA on the other. CONCLUSIONS: Levels of sIL-2R are increased, and rise before major exacerbations of SLE. Levels of sCD4 and sCD8, however, are not related to levels of sIL-2R, and do not reflect B-cell activation, nor disease activity during exacerbations of SLE. Thus for the clinical follow up of SLE measurement of levels of sCD4 or sCD8 is of limited value.

Adult↗
PubMed1994

Anti-neutrophil cytoplasmic antibodies: a new class of autoantibodies in glomerulonephritis, vasculitis and other inflammatory disorders.

Anti-neutrophil cytoplasmic antibodies (ANCA) constitute a new group of antibodies that are directed against myeloid proteins. Several antigens recognized by ANCA have been described. Antibodies directed to proteinase 3, myeloperoxidase and/or elastase are closely associated with necrotizing systemic vasculitis and/or necrotizing and crescentic glomerulonephritis. Changes in levels of anti-proteinase 3 in generally reflect disease activity in Wegener's granulomatosis. The diagnostic significance of other or still unknown specificities has not yet been definitely established. Recent data from in vitro and in vivo models suggest a role for ANCA in the pathogenesis of systemic vasculitides and/or necrotising and crescentic glomerulonephritis.

Antibodies, Antineutrophil Cytoplasmic↗