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C G Kallenberg

Publications and source records attributed to C G Kallenberg.

At least 91 records · Page 5Linked to original sources
PubMed1997

The predictive value of fluctuations in IgM and IgG class anti-dsDNA antibodies for relapses in systemic lupus erythematosus. A prospective long-term observation.

OBJECTIVE: This study investigated the predictive value of rises in IgM class antibodies against double stranded DNA (anti-dsDNA) for ensuing relapses in systemic lupus erythematosus (SLE) in comparison with rises in IgG class antibodies. In addition, it was analysed whether rises in IgM class anti-dsDNA were associated with specific clinical manifestations of SLE. METHODS: Thirty four of a cohort of 72 SLE patients who were positive for IgM class anti-dsDNA at the start of the study or at the time of a relapse were analysed monthly for class specific anti-dsDNA levels during a median observation period of 19.6 months. Disease activity was scored according to the SLE Disease Activity Index. Anti-dsDNA were measured by IgM and IgG class enzyme linked immunosorbent assay (ELISA) and by Farr assay. RESULTS: During the study 18 of 34 patients experienced 26 relapses. Twenty two (85%) of the relapses were accompanied by a positive test for IgM class anti-dsDNA by ELISA, 23 (89%) were positive for IgG class anti-dsDNA by ELISA, and 25 (96%) were positive by Farr assay. Patients with rises in IgG class anti-dsDNA by ELISA or in anti-dsDNA by Farr assay had a significantly higher cumulative risk for relapses than patients without those increases (p = 0.04 and p = 0.03, respectively). This was not the case for rises in IgM class anti-dsDNA (p = 0.16). Moreover, a rise in IgM class anti-dsDNA before a relapse was not associated, expressed in terms of odds ratios, with specific clinical manifestations of SLE. CONCLUSION: Relapses of SLE are frequently accompanied by IgM class anti-dsDNA. Rises of IgM class anti-dsDNA, in contrast with rises in IgG class anti-dsDNA, are not a sensitive tool for predicting a relapse and are not associated with specific clinical manifestations of SLE.

Adolescent↗
PubMed1997

[Sjögren's syndrome. Consequences for oral health].

Sjögren's syndrome is an auto-immune disease involving exocrine glands causing amongst others xerostomia and dry eyes. Many other tissues may be affected as well. Early recognition of this disease may help to alleviate signs and symptoms and is, thus, important. The aim of this paper is to provide the dentist with knowledge to enable him to timely diagnose the oral component of Sjögren's syndrome as well as to give guidelines for the treatment.

Diagnosis, Differential↗
PubMed1997

Systemic injection of products of activated neutrophils and H2O2 in myeloperoxidase-immunized rats leads to necrotizing vasculitis in the lungs and gut.

The strong association of anti-neutrophil cytoplasmic antibodies with various forms of systemic vasculitis suggests a role for these autoantibodies in the pathophysiology of systemic vasculitis. In the present study, we tested the hypothesis that release of neutrophil lysosomal enzymes in the presence of an anti-myeloperoxidase (anti-MPO) immune response may underlie the development of systemic vasculitis. Brown Norway rats were immunized with MPO in complete Freund's adjuvant or complete Freund's adjuvant alone. Two weeks after immunization, rats bad developed antibodies to human and rat MPO as measured by enzyme-linked immunosorbent assay. Next, rats were intravenously infused with 400 micrograms of a human neutrophil lysosomal extract containing 200 micrograms of MPO followed by 0.5 ml of a 1 mmol/L solution of H2O2 through a cannula inserted into the right jugular vein. Rats were sacrificed at 4 hours, 24 hours, 7 days, or 14 days, and several organs (lungs, heart, liver, spleen, gut, and kidneys) were examined for vasculitic lesions and inflammatory cell infiltrates. Macroscopically, patchy hemorrhagic spots were observed in the lungs and gut of MPO-immunized rats at days 7 and 14 after systemic infection of the neutrophil lysosomal extract and H2O2. Such changes were not observed at earlier time points or in control immunized rats. Histologically, the lungs of MPO-immunized rats sacrificed at days 7 and 14 showed patchy inflammatory cell infiltrates associated with vasculitis, granuloma formation, giant cells, and foci of hemorrhage. At 14 days, early signs of fibrosis were found with deposition of collagen and proliferation of fibroblasts. Furthermore, a prominent leukocytoclastic vasculitis was found in the small intestine of these rats characterized by fibrinoid necrosis and an extensive neutrophilic infiltrate. No inflammatory changes were found in the other organs studied (heart, liver, spleen, and kidneys). Control immunized rats, sacrificed at days 7 and 14 showed only some small foci of inflammatory infiltrates in the lungs whereas no inflammatory changes were found in the gastrointestinal tract. These studies show that release of products from activated neutrophils in the presence of anti-MPO autoantibodies may be relevant to the pathogenesis of anti-MPO-associated vasculitides.

Animals↗
PubMed1996

Development and standardization of solid phase assays for the detection of anti-neutrophil cytoplasmic antibodies (ANCA). A report on the second phase of an international cooperative study on the standardization of ANCA assays.

Anti-neutrophil cytoplasmic antibodies (ANCA) are diagnostic markers for systemic vasculitis. They are classically detected by an indirect immunofluorescence test using normal donor neutrophils as substrate. This assay lacks antigenic specificity and is not quantitative. The 'EC/BCR Project for ANCA Assay Standardization' is an international collaboration study with the aim to develop and standardize solid phase assays for ANCA detection. In this part of the study the isolation and characterization of proteinase-3 and myeloperoxidase, the two main target molecules for ANCA, and the development and standardization of ELISAs with these antigens are described. Six laboratories successfully isolated purified proteinase-3 preparations that could be used. Three of these preparations, together with one myeloperoxidase preparation, were subsequently used for ANCA testing by ELISA. The ELISA technique was standardized in two rounds of testing in the 14 participating laboratories. The coefficient of variation of these new assays decreased from values of approx. 50% in the first round to approx. 20% in the second round. We conclude that purified proteinase-3 and myeloperoxidase can be used in standardized ELISAs for ANCA detection. Whether such procedures offer advantages over the IIF test will be determined in a prospective clinical study.

Antibodies, Antineutrophil Cytoplasmic↗
PubMed1996

Trimethoprim-sulfamethoxazole (co-trimoxazole) for the prevention of relapses of Wegener's granulomatosis. Dutch Co-Trimoxazole Wegener Study Group.

BACKGROUND: Respiratory tract infections may trigger relapses in patients with Wegener's granulomatosis in remission. Uncontrolled data have suggested that treatment with trimethoprim-sulfamethoxazole (co-trimoxazole) may be beneficial. METHODS: We conducted a prospective, randomized, placebo-controlled study of the efficacy of co-trimoxazole (800 mg of sulfamethoxazole and 160 mg of trimethoprim) given twice daily for 24 months in preventing relapses in patients with Wegener's granulomatosis in remission during or after treatment with cyclophosphamide and prednisolone. Relapses and infections were assessed with predefined criteria based on clinical, laboratory, and histopathological findings. Patients were evaluated at least once every three months for signs of disease activity, compliance with the treatment regimen, side effects of the therapy, and evidence of infections. Titers of serum antineutrophil cytoplasmic antibodies were measured serially. RESULTS: Forty-one patients were assigned to receive co-trimoxazole, and 40 to receive placebo. In 8 of the 41 patients in the co-trimoxazole group (20 percent), the drug had to be stopped because of side effects. According to life-table analysis, 82 percent of the patients remained in remission at 24 months, as compared with 60 percent of the patients in the placebo group (relative risk of relapse, 0.40; 95 percent confidence interval, 0.17 to 0.98). There were fewer respiratory tract infections (P = 0.005) and non-respiratory tract infections (P = 0.05) in the co-trimoxazole group than in the placebo group. There were no significant differences in antineutrophil cytoplasmic antibody titers at any time. Proportional-hazards regression analysis identified treatment with co-trimoxazole as an independent factor associated with prolonged disease-free survival and a positive antineutrophil cytoplasmic antibody test at the start of treatment as a risk factor for relapse. CONCLUSIONS: Treatment with co-trimoxazole reduces the incidence of relapses in patients with Wegener's granulomatosis in remission.

Adult↗
PubMed1996

Anti-dsDNA production coincides with concurrent B and T cell activation during development of active disease in systemic lupus erythematosus (SLE).

The objective was to serially analyse T and B cell activation in relation to autoantibody production during the development of relapses in SLE. In a prospective study we serially analysed, by flow cytometry, T cell activation in relation to B cell activation and anti-dsDNA production in quiescent SLE and during the development of a clinical relapse. In addition, we related changes in T and B cell activation to changes in levels of anti-dsDNA and total IgG. During periods with clinically quiescent disease, the expression of activation markers on T cells (IL-2R and HLA-DR) and B cells (CD38) was persistently higher in SLE than in healthy controls (P < 0.001). Percentages of CD20+ CD38+ B cells were related to levels of total IgG (P < 0.02), but not to levels of anti-dsDNA. Development of disease activity was paralleled by an increase in the percentages of CD4+ T cells (P < 0.005) and CD20+ CD38+ B cells (P < 0.001), which were interrelated. Increases in B cell activation were related to increases in levels of anti-dsDNA (P < 0.005), but not to changes in total IgG levels. B cells expressing high levels of CD38 spontaneously produced IgG class anti-dsDNA in vitro. Persistence of activated B cells during periods with clinically quiescent disease in SLE seems to underly hypergammaglobulinaemia but not anti-dsDNA production. Prior to clinical disease activity, further activation of T and B cells occurs, which is paralleled by rises of anti-dsDNA but not of total IgG. This suggests that the production of anti-dsDNA is a T cell-dependent antigen-driven process, which is independent of the polyclonal activation of the immune system inherent to the disease.

ADP-ribosyl Cyclase↗
PubMed1996

Elastase, but not proteinase 3 (PR3), induces proteinuria associated with loss of glomerular basement membrane heparan sulphate after in vivo renal perfusion in rats.

Elastase, but not PR3, induces proteinuria associated with loss of glomerular basement membrane (GBM) heparan sulphate after in vivo renal perfusion in rats. PR3 and elastase are cationic neutral serine proteinases present in the azurophilic granules of polymorphonuclear leucocytes. Release of these proteolytic enzymes along the glomerular capillary wall may induce glomerular injury. Here, we investigated the effects of PR3 and elastase on the induction of proteinuria and glomerular injury after renal perfusion of these enzymes in Brown-Norway rats. Perfusion of active elastase induced a dose-dependent proteinuria 24h after perfusion, while inactivated elastase did not. Perfusion of comparable amounts of active PR3 did not induce proteinuria. Light and electron microscopy showed no morphological abnormalities in any experimental group. However, immunohistology revealed that proteinuria occurring after perfusion of active elastase was associated with a strong reduction in intraglomerular expression of the heparan sulphate side chain and, to a lesser extent, of the protein core of heparan sulphate proteoglycans (HSPG). In vitro, both elastase and PR3 digested HSPG. However, PR3 bound to a lesser extent to HSPG than elastase. We conclude that elastase, but not PR3, induces proteinuria after in vivo renal perfusion. This differential effect probably relates to different binding to the GBM of those enzymes due to differences in their isoelectric points. Degradation of heparan sulfate proteoglycans, leading to the disappearance of their side chains that contribute to the polyanionic structure of the GBM, appears to be involved in the induction of proteinuria after perfusion of elastase.

Animals↗
PubMed1996

Antineutrophil cytoplasmic antibodies in systemic lupus erythematosus.

Antineutrophil cytoplasmic antibodies (ANCA) with specificity for proteinase-3 (PR3) are associated with Wegener's granulomatosis, and ANCA directed to myeloperoxidase (MPO) with other idiopathic vasculitides. Inflammation of small-sized blood vessels is a hallmark of systemic lupus erythematosus (SLE). We evaluated the prevalence of ANCA in SLE, their antigenic specificities, and their possible relation to clinical disease patterns and activity. Plasma samples from 84 patients with SLE were tested for ANCA during remission. Plasma samples from the 25 patients who relapsed during a follow-up of 32 months were serially analysed for ANCA in a 6 month period preceding and including the relapse. The presence of ANCA was assessed by indirect immunofluorescence (IIF) and ELISA for antibodies to PR3, MPO, lactoferrin (LF), elastase (HLE) and cathepsin-G (CG). We related the presence of ANCA to disease patterns, activity and duration. ANCA by IIF were difficult to interpret dut to the presence of antinuclear antibodies (ANA). By ELISA, we found no anti-PR3 or anti-HLE. Anti-MPO (n = 7), anti-LF (n = 13) and anti-CG (n = 10) were detected, generally in low titres. The presence of ANCA of defined specificity was not associated with specific clinical subsets. The prevalence of ANCA was higher in patients who developed relapses than in those who did not (P < 0.01). However, levels of ANCA did not fluctuate in the period preceding the relapse. ANCA of various specificities occur in SLE. Their presence is not associated with specific clinical disease entities. The higher frequency of ANCA in relapsing patients compared to those who do not relapse may suggest that ANCA are involved in disease expression. Their diagnostic significance is limited.

Adult↗
PubMed1996

Anti-double stranded DNA antibodies in systemic lupus erythematosus: detection and clinical relevance of IgM-class antibodies.

We determined the discriminative value of the Farr assay in comparison to ELISA and Crithidia luciliae immunofluorescence assay (IFT) for detecting anti-dsDNA antibodies as a diagnostic tool for systemic lupus erythematosus (SLE). Special attention was paid to the diagnostic significance of IgM-class anti-dsDNA. Sera were analyzed from 74 patients with SLE, 257 patients with other auto-immune diseases, and 50 healthy controls. All sera were tested for anti-dsDNA using the IFT (anti-total immunoglobulin conjugate), ELISA (anti-IgG and anti-IgM conjugates), and the 125I Farr assay. Specificity and sensitivity for a diagnosis of SLE appeared to be highest for the Farr. All SLE sera with IgM-class anti-dsDNA without IgG-class anti-dsDNA as detected by ELISA, were positive when tested by the Farr assay. In contrast, most of the sera with IgM-class anti-dsDNA as detected by ELISA from patients with diseases other than SLE were negative when tested by Farr assay.

Adolescent↗
PubMed1996

Autoantibodies to myeloperoxidase aggravate mild anti-glomerular-basement-membrane-mediated glomerular injury in the rat.

Autoantibodies to myeloperoxidase (MPO) are present in sera from patients with various forms of vasculitis-associated glomerulonephritis. Evidence for a pathogenic role of anti-MPO antibodies has been provided mainly by in vitro studies. We studied the pathogenic role of autoantibodies to MPO in a rat model of mild immune-mediated glomerular injury. Brown Norway rats were immunized with human MPO in complete Freund's adjuvant or with complete Freund's adjuvant alone. At 2 weeks after immunization, rats had developed antibodies to human and rat MPO as detected by indirect immunofluorescence, enzyme-linked immunosorbent assay, and immunoprecipitation. At this time point, rats were intravenously injected with a subnephritogenic dose of 150 micrograms of rabbit anti-rat GBM. Rats were sacrificed at 4 hours, 24 hours, 4 days, and 10 days after antibody administration. Control immunized rats developed mild glomerulonephritis characterized by slight proteinuria at day 10 (14.8 +/- 8.1 mg/24 hours) and moderate intraglomerular accumulation of ED1+ macrophages. Crescent formation, tuft necrosis, and tubular atrophy were not observed in those rats. In contrast, rats immunized with MPO developed severe glomerulonephritis characterized by the early occurrence of severe hematuria, marked proteinuria at day 10 (76.2 +/- 18.2 mg/24 hours), and massive glomerular deposition of fibrin. Complement and rat IgG were present in insudative lesions, but no linear pattern along the glomerular capillary wall was observed. By light microscopy, severe glomerular lesions were found at day 10 consisting of crescent formation and fibrinoid necrosis of capillary loops. In the interstitium, tubular necrosis and atrophy and marked interstitial mononuclear infiltration were found in conclusion, autoantibodies to MPO severely aggravate subclinical anti-GBM disease demonstrating their in vivo pathogenic potential.

Animals↗
PubMed1995

Skewed distribution of IgG Fc receptor IIa (CD32) polymorphism is associated with renal disease in systemic lupus erythematosus patients.

OBJECTIVE: Fc gamma receptors of class IIa (Fc gamma RIIa) occur in 2 allelic forms, with either a low (IIa-R131) or a high (IIa-H131) affinity for complexed IgG2 and IgG3. This polymorphism might have implications for the handling of immune complexes. Therefore, we determined the distribution of the Fc gamma RIIa allotypes in patients with systemic lupus erythematosus (SLE), with or without a history of lupus nephritis. METHODS: We studied 95 unrelated white European patients with SLE, as defined by the American College of Rheumatology criteria, 50 of whom had a history of lupus nephritis, and 69 healthy white European control subjects. Fc gamma RIIa allotypes were determined by immunophenotyping of blood monocytes. RESULTS: It was found that lupus nephritis was significantly associated with the "low affinity" Fc gamma RIIa R/R131 allotype and with the R131 allele, compared with healthy controls. No significant association was found upon comparison of groups with and without nephritis. CONCLUSION: SLE patients with a history of lupus nephritis have an abnormal distribution of Fc gamma RIIa allotypes. Fc gamma RIIa may well play a role in the pathogenesis of lupus nephritis, since IIa-R/R131 SLE patients seem to have a higher incidence of developing this complication.

Adult↗