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Biomedical subjects

J Wieslander

Publications and source records attributed to J Wieslander.

132 records · Page 8Linked to original sources

Urinary excretion of the carboxy terminal domain of type IV collagen is associated with kidney size and function in IDDM.

We evaluated whether urinary excretion of the carboxy terminal domain (NC1) of Type IV collagen is associated with glomerular filtration rate and kidney size in Type I (insulin-dependent) diabetes mellitus (IDDM). Urinary excretion rate of NC1, glomerular filtration rate (GFR), and kidney size were measured in 16 men with Type I diabetes. Their mean age was 33.3 +/- 6.1 years with a duration of diabetes of 14.9 +/- 3.7 years (mean +/- SD). The urinary excretion rate of NC1 was higher in the diabetic patients than in 18 healthy control subjects. Urinary excretion of NC1 was associated with both kidney size, parenchymal width, and GFR (r = 0.73, p = 0.001; r = 0.63, p = 0.009; r = 0.53, p = 0.04, respectively). The exact relationship between these factors and basement membrane turnover/synthesis remains to be elucidated.

Adult↗

How and why should we detect ANCA?

Antineutrophil cytoplasmic antibodies (ANCA) have become an established tool for the diagnosis of systemic vasculitis. The major role for ANCA testing is in diagnosing renal insufficiency of unknown origin, where a positive test indicates whether the patient will benefit from immunosuppressive treatment or not. A negative test result almost completely rules out the presence of systemic vasculitis. In this clinical setting the major antigens for ANCA are proteinase 3 and myeloperoxidase, and antibodies to these antigens can best be tested by ELISA. In other clinical settings like inflammatory bowel disease, arthritis and so on, several other ANCA specificities have been described and the IIF test is preferred. However, the clinical value of these somewhat more esoteric specificities is doubtful. New developments in assay techniques and better knowledge of specific epitopes will lead to tools for the improved diagnosis as well as follow up of patients during treatment, as has already been seen with the capture assay for PR3-ANCA.

Antibodies, Antineutrophil Cytoplasmic↗

Antibodies against terminal galactosyl (alpha 1-3) galactose epitopes in systemic sclerosis (scleroderma).

Sera from 224 patients with systemic sclerosis (scleroderma) were analyzed for circulating antibodies against an antigenic determinant characterized by two molecules of galactose in alpha 1-3 linkage. About 45% of the patients were found to have values above the normal range. The mean antibody level was significantly higher than that found in normal subjects (p less than 0.001) or in patients with primary Raynaud's phenomenon who were included as controls. The mean level of anti-Gal antibodies correlated with the degree of skin and internal organ involvement, as well as with the presence of progression or inflammation. Furthermore, when patients with early onset disease were analyzed, high levels of anti-Gal antibodies were present in the subgroups characterized by evidence of progression or inflammation, whereas patients with stable disease did not differ from the controls. We conclude that humoral immunity against Gal alpha 1-3 Gal is an early feature of scleroderma, may be important for its pathogenesis, and may provide a more sensitive tool to detect disease activity.

Adolescent↗

Pseudomonas-induced lung damage in cystic fibrosis correlates to bactericidal-permeability increasing protein (BPI)-autoantibodies.

OBJECTIVE: Lung damage is the most common cause of death in cystic fibrosis (CF). It is induced by bacterial colonization and inflammatory activity perpetuates its course. Autoantibodies directed against BPI (bactericidal permeability increasing protein), called BPI-ANCA, have recently been associated with cystic fibrosis. Here we confirm this association and evaluate the relation between ANCA and total IgG level as they relate to bacterial colonization, pulmonary function, and musculoskeletal symptoms. METHODS: BPI-ANCA, MPO-ANCA, and PR3-ANCA were measured with ELISA in 46 adult patients with CF. Total IgG was determined by immunoturbidimetry. Results were correlated to bacterial colonization, lung function and musculoskeletal symptoms. RESULTS: BPI-ANCA was found in 33 patients. In the whole group, both BPI-ANCA and total IgG were inversely correlated to lung function, but in patients chronically colonized with Pseudomonas aeruginosa (P. aeruginosa), BPI-ANCA alone was correlated to lung damage (p = 0.01). Median lung function, measured as forced expiratory volume in 1 second, in P. aeruginosa colonized patients with high levels of BPI-ANCA was 43% of the predicted value. In BPI-ANCA negative, the corresponding figure was 83%. In patients not colonized with P. aeruginosa, this relation was less evident. No correlation between ANCA and musculoskeletal symptoms was seen. CONCLUSION: P. aeruginosa induced lung damage in CF patients is associated with the presence of BPI-ANCA. P. aeruginosa colonized patients without BPI-ANCA have almost normal lung function. We suggest that BPI-ANCA discriminate P. aeruginosa colonized CF patients with severe lung damage from those whose disease is less destructive. Vasculitis like symptoms in CF are not ANCA associated.

Adult↗

Characterization of monoclonal antibodies to proteinase-3 and application in the study of epitopes for classical anti-neutrophil cytoplasm antibodies.

Wegener's granulomatosis is associated with autoantibodies (classical antineutrophil cytoplasm antibodies, c-ANCAs) to a serine protease called proteinase-3. In this study three IgG class monoclonal antibodies, designated 4A3, 4A5 and 6A6, against proteinase-3 were generated to study the immune response of c-ANCA-positive patients. All monoclonal antibodies were tested by immunofluorescence staining of human granulocytes and gave a staining pattern identical to the pattern obtained with sera from patients with Wegener's granulomatosis. On protein transfer blots of neutrophil alpha-granule extract, all monoclonal antibodies stained a 29-kD protein band corresponding to proteinase-3. Also, in a direct binding ELISA with alpha-granule extract as antigen, binding of the monoclonal antibodies to the antigen could be completely inhibited by adding a pure preparation of proteinase-3. In the ELISA type of competition experiments, none of the monoclonal antibodies could substantially inhibit binding of any of the other antibodies to the antigen, indicating that all monoclonal antibodies recognize separate epitopes on the antigen. The same conclusion was reached from experiments by real-time competition analysis using a Pharmacia BIAcore system. The monoclonal antibodies were used to study whether some epitopes on proteinase-3 are preferred by patient autoantibodies. A total of 36 patients sera was tested by competing for autoantibody binding to proteinase-3 with the monoclonal antibodies in an ELISA. Autoantibody binding to proteinase-3 could be partially or completely inhibited by either the 4A5 (50% of the sera) or by the 6A6 antibody (11%). The 4A3 antibody could only partially inhibit 8 of the sera (22%).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗