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- Carlsson, A, et al.
(författare)
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Pseudomonas-induced lung damage in cystic fibrosis correlates to bactericidal-permeability increasing protein (BPI)-autoantibodies
- 2003
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Ingår i: Clinical and Experimental Rheumatology. - 1593-098X. ; 21:Suppl. 32, s. 95-100
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Tidskriftsartikel (refereegranskat)abstract
- 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 I 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.
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- Persson, Ulf, et al.
(författare)
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Patients with Goodpasture's disease have two normal COL4A3 alleles encoding the NC1 domain of the type IV collagen {alpha}3 chain.
- 2004
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Ingår i: Nephrology Dialysis Transplantation. - : Oxford University Press (OUP). - 1460-2385 .- 0931-0509. ; 19:8, s. 2030-2035
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Tidskriftsartikel (refereegranskat)abstract
- Background. Goodpasture's disease (GP) is a rare but severe disease characterized by anti-glomerular basement membrane antibodies, rapidly progressive glomerulonephritis and lung haemorrhage. The autoantibodies are restricted to a narrow epitope region on the NC1 domain of the alpha3 chain of type IV collagen. GP is strongly associated with major histocompatibility complex (MHC) allele HLA DRB1-15. Recent research, however, has failed to identify a T-cell epitope with molecular characteristics that explain the relationship between the MHC class II molecule and the autoantibody generation. We hypothesized that an as yet unidentified sequence variant in exons 48-52 of the COL4A3 gene that encodes the NC1 domain of the type IV collagen alpha3 chain could generate a new peptide sequence that, through interaction with specific MHC class II molecules, would increase the risk of developing GP. Methods. All patients previously treated for GP at the Lund and Malmo University Hospitals, who were alive at the time of the study, were asked to participate. DNA was extracted from leukocytes and subjected to genomic tissue typing and sequencing of the COL4A3 gene exons 48-52. Results. All 15 patients in the study had a nucleotide sequence in the COL4A3 gene encoding a protein identical to GenBank entry NM_000091. HLA D allele distribution was in line with previous publications, showing a strong positive association between HLA DRB1-15, HLA DQB1-6 and GP (P < 0.02). Of the 15 GP patients, 73% carried HLA DRB1-15 and 87% carried the HLA DQB1-6 antigen. Corresponding figures for the controls were 27 and 50%. Conclusion. This study effectively falsifies the hypothesis that a minor alteration in the COL4A3 gene could be a major factor in the aetiology of GP. Scandinavian GP patients have an MHC distribution similar to that which has been described previously for Anglo-Saxon patients.
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