Applicability of saliva as a diagnostic fluid in Sjögren's syndrome.
Explore the source record for details and available documents.
Adult↗
Biomedical subjects
C G Kallenberg
Publications and source records attributed to C G Kallenberg.
Antimyeloperoxidase-associated proliferative glomerulonephritis: an animal model.
To develop an animal model for antimyeloperoxidase (MPO)-associated necrotizing crescentic glomerulonephritis (NCGN), we immunized Brown Norway rats with MPO and localized a neutrophil lysosomal enzyme extract, primarily consisting of MPO and elastinolytic enzymes, plus H2O2, the substrate of MPO, to the glomerular basement membrane (GBM). Upon immunization rats developed antibodies and positive skin tests to MPO. After unilateral perfusion of the left kidney with the lysosomal enzyme extract and H2O2, MPO and immunoglobulin (Ig)G localized transiently along the GMB. At the time of maximal inflammation, at 4 and 10 d after perfusion, MPO, IgG, and C3 could not be detected anymore. MPO-immunized rats perfused with the lysosomal enzyme extract and H2O2, in contrast to control-immunized and/or control-perfused rats, developed a proliferative GN characterized by intra- and extracapillary cell proliferation, ruptured Bowman's capsule, periglomerular granulomatous inflammation, and formation of giant cells. Monocytes, polymorphonuclear leukocytes (PMN), and to a far lesser extent T cells were found in the glomeruli. Interstitial infiltrates consisted of monocytes, PMN, and T cells. Granulomatous vasculitis of small vessels was found at 10 d after perfusion. The proliferative NCGN in this rat model closely resembles human anti-MPO-associated pauci-immune NCGN, and enables the study of the pathophysiology of anti-MPO-associated NCGN.
Animals↗
Antineutrophil cytoplasmic antibodies in rheumatoid arthritis. Characterization and clinical correlations.
OBJECTIVE: To study the prevalence, interrelationships, and target antigens of antineutrophil cytoplasmic antibodies (ANCA) in rheumatoid arthritis (RA) and to relate their presence to disease duration and to the occurrence of extraarticular manifestations, including vasculitis. METHODS: Sera from 94 patients with RA (31 with recent-onset disease, 35 with longstanding disease but without extraarticular manifestations, and 28 with extraarticular disease) were studied for the presence of ANCA by indirect immunofluorescence. All sera were tested by enzyme-linked immunosorbent assay (ELISA) for the presence of antibodies to proteinase 3, myeloperoxidase (MPO), elastase, lactoferrin (LF), and cathepsin G (CG), and by Western blotting for antibodies to neutrophil proteins. RESULTS: Seventy percent of the 94 sera showed staining of the nuclei of ethanol-fixed neutrophils; 32% of the 94 were proven to have ANCA, as manifested by their cytoplasmic staining pattern on paraformaldehyde-fixed neutrophils. In the ELISA, 19 sera reacted with LF, 1 with MPO, and 1 with CG. By Western blotting, 21 sera reacted with LF, and 15 reacted with previously unknown polypeptides (7 sera with a 67/66-kd doublet and 8 with a 63/54-kd doublet). Neither of these antibodies was associated with a particular subset of the disease, but the prevalence of the antibodies tended to increase among patients with longstanding disease. CONCLUSION: ANCA in RA patients are directed toward diverse cytoplasmic antigens of the neutrophil, in particular, LF and other, not yet fully characterized polypeptides. The antibodies are not a marker for a disease subset, but are probably a corollary of chronic inflammation.
Adolescent↗
Induction of an humoral and cellular (auto) immune response to human and rat myeloperoxidase(MPO) in Brown-Norway(BN), Lewis and Wistar Kyoto(WKY) rat strains.
Anti-MPO and anti-proteinase 3 antibodies are strongly associated with certain forms of vasculitis and glomerulonephritis and a pathophysiological role for the antibodies has been hypothesized (Kallenberg et al. 1991). To test this hypothesis WKY, Lewis and BN rats were immunized with human MPO. BN rats developed a strong humoral response, cross reacting with autologous MPO, and Lewis rats a strong cellular response to human MPO.
Animals↗
Perinuclear antineutrophil cytoplasmic antibodies (p-ANCA): clinical significance and relation to antibodies against myeloid lysosomal enzymes.
In a prospective study of 27 months duration p-ANCA were found in 120 patients. 35% of these patients had vasculitis and/or glomerulonephritis. 28% of the p-ANCA positive sera reacted with myeloid lysosomal enzymes.
Antibodies, Antineutrophil Cytoplasmic↗
Anti-neutrophil cytoplasmic antibodies in giant cell arteritis and polymyalgia rheumatica.
Antineutrophil cytoplasmic antibodies (ANCA) were demonstrated in all sera from 11 patients with active giant cell arteritis (GCA) using indirect immunofluorescence on 9% paraformaldehyde(PF)-fixed neutrophils according to Pryzwanski (median titer 1:256, range 1:64 to 1:512). After treatment during inactive disease titers decreased in all sera. Eight out of 9 sera from patients with active polymyalgia rheumatica (PMR) produced a cytoplasmic staining on Pryzwanski-fixed neutrophils in low titers (median titer 1:16, range 0 to 1:32), as did 8 out of 25 sera from healthy blood donors. None of the sera were positive for antibodies to defined antigens, i.e. proteinase-3, human leucocyte elastase, myeloperoxidase and lactoferrin as detected by ELISA. GCA seems to be associated with ANCA of as yet unknown specificity.
Aged↗
Serum markers of T-cell activation in relapses of Wegener's granulomatosis.
Levels of soluble IL-2 receptor (sIL-2R), soluble CD4 (sCD4) and CD8 (sCD8) were measured by sandwich ELISA as markers for T-cell activation in serial serum samples drawn monthly from 16 patients showing 18 histologically proven relapses of Wegener's granulomatosis (WG). Levels of sIL-2R increased from 1162 U/ml (median, 95% CI 843 to 1814 U/ml) at three months before the relapse to 1684 U/ml (95% CI 1254 to 2202 U/ml) at the time of relapse for the whole group (P = 0.10). The 8 major relapses showed a profound rise in sIL-2R levels (P < 0.01). The level of sIL-2R at the moment of relapse correlated with the level of C-reactive protein (r = 0.547, P < 0.05) and with the disease activity score (r = 0.814, P < 0.001). There were no significant changes in levels of sCD4 or sCD8.
Antibodies, Antineutrophil Cytoplasmic↗
Antineutrophil antibodies in inflammatory bowel disease recognize different antigens.
Anti-neutrophil cytoplasmic antibodies (ANCA) were observed in 31 out of 68 sera (45%) from Ulcerative Colitis (UC) patients and in 13 out of 38 Crohn's Disease (CD) sera (34%). The presence of ANCA was not related to disease activity, nor to the localization of the disease manifestations. By Western Blotting ANCA showed reactivity with either lactoferrin, polypeptides occurring as a doublet of 66/67 kD MW, or polypeptides occurring as a doublet of 63/54 kD MW.
Antibodies, Antineutrophil Cytoplasmic↗
Anti-neutrophil cytoplasmic antibodies (ANCA) in autoimmune liver disease.
ANCA were detected in 67% of sera from patients with primary sclerosing cholangitis (n = 15), in 83% of sera from patients with autoimmune chronic active hepatitis (n = 18) and in 35% of sera from patients with primary biliary cirrhosis (n = 20). ANCA were not detected in non-autoimmune chronic liver diseases. Characterization studies of the antigens involved showed that ANCA in autoimmune liver disease are not directed against myeloperoxidase (mpo), proteinase 3 (pr3) or elastase (hle), but the ANCA in autoimmune liver disease show reactivity with lactoferrin, a 67/66 kD protein combination or a 63/54 kD protein combination on Western Blots.
Antibodies, Antineutrophil Cytoplasmic↗
Anti-myeloperoxidase antibodies in Churg-Strauss syndrome.
Explore the source record for details and available documents.
Autoantibodies↗
Neutrophil cytoplasmic autoantibodies after liver transplantation in patients with primary sclerosing cholangitis.
The immunopathogenic importance of neutrophil cytoplasmic autoantibodies in ulcerative colitis and primary sclerosing cholangitis is unknown. These autoantibodies were investigated before and after liver transplantation in 9 patients with primary sclerosing cholangitis. Sera from 10 patients transplanted for metabolic disorders or hemangioma served as controls. Before liver transplantation neutrophil cytoplasmic autoantibodies, producing a perinuclear pattern by indirect immunofluorescence on ethanol fixed neutrophils, were present in all patients with primary sclerosing cholangitis. A decline in titer was noted in the first months after liver transplantation. During long-term follow up, the autoantibodies remained present and most often the titer did not differ from before transplantation. They were not directed against proteinase 3, myeloperoxidase, elastase or lactoferrin. All but one of the control patients were negative for the autoantibody. No relation was seen, before or after transplantation, with ulcerative colitis or proctocolectomy. There was no recurrence of primary sclerosing cholangitis in any of the patients as judged by liver histology. We conclude that neutrophil cytoplasmic autoantibodies remain present after liver transplantation for primary sclerosing cholangitis and that its synthesis is not related to the presence of the diseased organ(s). The primary disease process in primary sclerosing cholangitis and ulcerative colitis may well be a disturbance of the immune system.
Adult↗
Overlapping syndromes, undifferentiated connective tissue disease, and other fibrosing conditions.
Connective tissue diseases (CTDs) frequently present as undifferentiated disorders that may or may not develop into one of the well defined CTDs. The natural evolution of the early undifferentiated CTDs is not well known. Some years ago a cooperative study was started on 410 patients with early CTD; within this group, 48 patients had early scleroderma. Raynaud's phenomenon has been recognized as an early sign of CTD. Several studies on Raynaud's phenomenon patients have shown that abnormal nailfold capillary patterns have prognostic significance for evolution to a CTD, particularly scleroderma. Mixed connective tissue disease (MCTD) is the prototype of an overlap syndrome. The relevance of defining MCTD as a separate disease entity has been challenged. Follow-up studies show that many patients originally diagnosed with MCTD develop a definite CTD, particularly scleroderma or systemic lupus erythematosus, within a few years. In patients with MCTD, primary pulmonary hypertension is an important cause of death. This condition seems to be associated with anticardiolipin antibodies. A number of case reports suggest that immunosuppressive treatment is of benefit in this almost always fatal condition. The main reason for describing MCTD as a separate entity is its association with antibodies to U1-RNP. Recent studies have suggested that the production of anti-U1-RNP is an antigen-driven process, but the nature of the trigger for its production has not been elucidated. Retroviral proteins do not appear to be involved. Antibodies to the protein part of the U1-RNP complex and antibodies to the RNA component have been described. Levels of anti-RNA antibodies seem to parallel disease activity in MCTD patients.(ABSTRACT TRUNCATED AT 250 WORDS)
Adolescent↗
Serum markers of T cell activation in relapses of Wegener's granulomatosis.
Levels of soluble IL-2 receptor (sIL-2R), soluble CD4 (sCD4) and CD8 (sCD8) were measured by sandwich ELISA as markers for T cell activation in serial serum samples from 16 patients showing 18 histologically proven relapses of Wegener's granulomatosis (WG). Levels of sIL-2R increased from 1065 U/ml (median, range 373-2345 U/ml) 6 months before the relapse to 1684 U/ml (median, range 486-3404 U/ml) at the moment of relapse for the whole group (P = 0.10). The eight major relapses showed a profound rise in sIL-2R levels, from 1008 U/ml (median, range 686-1553 U/ml) 6 months before the relapse, to 1994 U/ml (median, range 1469-3404 U/ml) at the moment of relapse (P < 0.01). The levels of sIL-2R at the moment of relapse were significantly higher at the eight major relapses than at the time of the 10 minor relapses (P < 0.05). Minor relapses were not accompanied by a significant rise in sIL-2R levels. Titres of antineutrophil cytoplasmic antibodies (ANCA) rose by two or more titresteps or from negative to positive in 15/18 patients during the 6 months period before the relapse. In all seven cases with both a rise of the ANCA titre and an at least 25% increase in sIL-2R levels, the rise in ANCA preceded the rise in sIL-2R by at least 1 month. The level of sIL-2R at the moment of relapse correlated with the level of C-reactive protein (r = 0.488, P < 0.05) and with the disease activity score (r = 0.824, P < 0.002). There were no significant changes in levels of sCD4 or sCD8, although the levels of sCD4 tended to be higher at the time of major relapses. We conclude that major relapses of Wegener's granulomatosis are accompanied by systemic T cell activation. T cell activation, however, does not appear to precede the rise in ANCA titre.
Antibodies, Antineutrophil Cytoplasmic↗
Bronchoalveolar lavage cell analysis and lung function impairment in patients with systemic lupus erythematosus (SLE).
We examined the relationship between peripheral blood and bronchoalveolar lavage (BAL) lymphocyte phenotypes and lung function in 19 patients with SLE, and evaluated their association with disease activity. Lung function assessment showed a mildly restrictive pattern with frequent impairment of transfer factor for carbon monoxide (T1,co) and diffusing capacity of the alveolocapillary membrane (Dm), of late-expiratory airflow rates and with a high prevalence of increased airway resistance. T1,co, Kco and Dm correlated inversely with the numbers of CD8+ cells and CD56+/CD16+/CD3- (NK) cells in BAL. Oxygen radical production, both by stimulated and unstimulated BAL cells and blood polymorphonuclear leucocytes (PMN) was significantly increased in SLE. In comparison with healthy controls, patients with SLE had a lower percentage of CD19+ B cells in the BAL versus an increased percentage of these cells in peripheral blood. HLA-DR expression on CD4+ and CD8+ lung lymphocytes was markedly increased in SLE. Current SLE disease activity was not associated with changes in BAL or peripheral blood lymphocyte phenotypes. Our data suggest that an ongoing cell-mediated immune response is present in the lungs in SLE, particularly involving activated CD8+ T cells and CD56+/CD16+/CD3- NK cells. It is associated with up-regulated local production of oxygen radicals and with impaired pulmonary diffusing capacity. This inflammatory process seems to be independent of general SLE disease activity.
Adult↗
Higher anti-heparan sulphate reactivity during systemic lupus erythematosus (SLE) disease exacerbations with renal manifestations; a long term prospective analysis.
Cross-reactive antibodies against heparan sulphate (HS) have been suggested to play a role in initiating renal disease in SLE. Recently, we found that HS-reactivity is mediated by anti-DNA antibodies complexed with DNA and histones. To evaluate the clinical significance of anti-HS reactivity, we studied prospectively a cohort of 72 consecutive SLE patients, of whom 22 experienced 40 exacerbations. In 20 of these exacerbations renal symptoms were present. In these 20 exacerbations significantly higher anti-DNA (median 1:160) and anti-HS (median 1:30) titres were detected compared with exacerbations without renal manifestations (median 1:60 for anti-DNA and negative for anti-HS). There were no correlations with other symptoms of SLE. Anti-HS titres showed a significant correlation with anti-DNA antibody titres (rs = 0.57, P < 0.05). Anti-HS without anti-DNA reactivity was never detected. Some SLE patients showed a high anti-DNA titre without anti-HS reactivity, suggesting that not all anti-DNA antibodies are able to bind to histone/DNA complexes and thus to exhibit anti-HS reactivity. Our findings indicate that anti-HS reactivity is correlated with renal disease in SLE.
Antibodies, Antinuclear↗
B cell activation in clinically quiescent systemic lupus erythematosus (SLE) is related to immunoglobulin levels, but not to levels of anti-dsDNA, nor to concurrent T cell activation.
In clinically quiescent SLE hypergammaglobulinaemia, presence of autoantibodies, and increased soluble IL-2 receptors (sIL-2R) have been reported, suggesting persistent B as well as T cell activation. In contrast, the primary immune response to test antigens is markedly decreased. To analyse these phenomena at a cellular level, we undertook a cross-sectional study on 13 non-active SLE patients and 15 controls. We determined the composition of lymphocyte subsets with special attention to activation markers (CD25, HLA-DR, CD38) and the presence of naive T cells (CD45RO-), and related those findings to serological parameters. In non-active SLE patients the expression of activation markers on B cells and T cells was higher than in normal controls (P < or = 0.02), but was not interrelated. Percentages of activated B cells in SLE were related to levels of total IgG (P < 0.02) and IgM (P < 0.02) but not to anti-dsDNA, suggesting a disordered immune system also in clinically quiescent SLE. Numbers of CD4+ cells (P < 0.001) and CD4+CD45RO- cells (P < 0.05) were decreased. The latter finding might explain the anergy to primary test antigens in clinically quiescent SLE.
Adult↗
Relevance of classic anti-neutrophil cytoplasmic autoantibody (C-ANCA)-mediated inhibition of proteinase 3-alpha 1-antitrypsin complexation to disease activity in Wegener's granulomatosis.
In the sera of patients with Wegener's granulomatosis (WG), C-ANCA can be detected that are directed against proteinase 3 (PR3). We have previously observed that C-ANCA interfere with PR3 proteolytic activity and with complexation of PR3 with its major physiologic inhibitor, alpha 1-antitrypsin (alpha 1AT). In the present study we investigated whether this inhibitory effect of C-ANCA on PR3-alpha 1AT complexation correlates with clinical activity of WG. Serial serum samples of eight consecutive patients with histologically proven relapses of WG were tested. At the moment of relapse all sera revealed inhibitory activity towards PR3-alpha 1AT complexation (median 22%, range 10-59%). Disease activity score (r = 0.87, P < 0.02) and C-reactive protein (CRP) levels (r = 0.66, P < 0.1) correlated with C-ANCA inhibition of PR3-alpha 1AT complexation, while they did not correlate with the C-ANCA titre detected by indirect immunofluorescence (IIF) nor with IgG anti-PR3 antibody level measured by ELISA. The inhibitory effect of C-ANCA on PR3-alpha 1AT complexation had risen significantly at the moment of relapse compared with values 3 months (P < 0.05) and 6 months (P < 0.01) before relapse. Eight patients with established WG and positive for C-ANCA but without clinical evidence of relapse served as controls. In this group no inhibitory effect of C-ANCA on PR3-alpha 1AT complexation was observed in 7/8 patients sera. Sera of one control patient contained moderate C-ANCA inhibitory activity towards PR3-alpha 1AT complexation, which remained at a constant level during the 6 months period of observation. Thus, disease activity in WG appears to be more closely related to C-ANCA inhibitory activity towards PR3-alpha 1AT complexation.
Adult↗
Hydroxychloroquine treatment for primary Sjögren's syndrome: a two year double blind crossover trial.
OBJECTIVES: In 1985 and 1988 a positive effect of treatment of primary Sjögren's syndrome with hydroxychloroquine was reported in two small open studies. To investigate further the clinical and laboratory effects of hydroxychloroquine in primary Sjögren's syndrome a two year study was performed. METHODS: The design of the study included a prospective, placebo controlled, two year double blind crossover trial in 19 patients. RESULTS: A significant decrease in IgG and IgM and a tendency for a decrease in the erythrocyte sedimentation rate (ESR) during treatment with hydroxychloroquine compared with treatment with placebo were found. No beneficial clinical effect of the use of hydroxychloroquine as expressed in preference for treatment with hydroxychloroquine or placebo with regard to symptoms and signs of primary Sjögren's syndrome could be shown, however, nor any relevant change in tear gland activity and sequelae of peripheral tear function deficiency, nor salivary gland scintigraphy. CONCLUSIONS: The use of hydroxychloroquine at a dose of 400 mg daily taken over a 12 month period does not have a worthwhile clinical benefit in patients with primary Sjögren's syndrome despite an improvement of hyperglobulinaemia and slight changes in the ESR and IgM.
Adult↗