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Immunological aspects on cystic fibrosis lung disease

Carlsson, Malin LU (2007)
Abstract
In cystic fibrosis (CF) colonization of the airways with Pseudomonas aeruginosa is a major cause of deterioration and death. Host defence fails to clear the invading bacteria, which results in a chronic destructive inflammatory process. This thesis deals with factors in the interaction between bacteria and host defence that determine the extent of tissue damage caused by the bacteria.



(I) Autoantibodies against bactericidal/permeability increasing protein (BPI-ANCA) were measured in 46 CF patients and were found in a prevalence of 72 %. We found a strong correlation between BPI-ANCA concentration and lung damage, especially in P. aeruginosa colonized patients.



(II) Precence of BPI-ANCA was found to... (More)
In cystic fibrosis (CF) colonization of the airways with Pseudomonas aeruginosa is a major cause of deterioration and death. Host defence fails to clear the invading bacteria, which results in a chronic destructive inflammatory process. This thesis deals with factors in the interaction between bacteria and host defence that determine the extent of tissue damage caused by the bacteria.



(I) Autoantibodies against bactericidal/permeability increasing protein (BPI-ANCA) were measured in 46 CF patients and were found in a prevalence of 72 %. We found a strong correlation between BPI-ANCA concentration and lung damage, especially in P. aeruginosa colonized patients.



(II) Precence of BPI-ANCA was found to predict severe adverse outcome in the 46 adult patients after 5-7 years. BPI-ANCA was measured in 366 patients. The patients were followed prospectively and we found that the BPI-ANCA response occurred following colonization with P. aeruginosa. In all patients who were lung transplanted, the BPI-ANCA levels decreased. In patients who were colonized with P. aeruginosa and had no BPI-ANCA, median lung function was normal.



(III) Binding of mannan-binding lectin (MBL) may activate complement. About 10% of the population are MBL-deficient. When investigating 114 CF patients we found no correlation between MBL pathway deficiencies and severe lung disease. The levels of MBL in serum were found to be higher in CF patients than in controls.



(IV) Isolates of P.aeruginosa from CF patients were collected and their interactions with human cells were investigated. We found that isolates from patients with positive BPI-ANCA had white phenotypes and evoked mild inflammatory responses.



Conclusions: We suggest that P. aeruginosa is a risk factor for severe lung damage in CF particularly if accompanied by a rise in BPI-ANCA in serum. The BPI-ANCA response was secondary to colonization with P. aeruginosa, BPI-ANCA associated strains of P. aeruginosa evoked a mild inflammatory response. We speculate that inadequate inflammation impairs host defence, and thus allows bacterial proliferation, which apparently is a disadvantage to the host. MBL-deficiency was not a risk factor for severe lung disease in the studied cohort. (Less)
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author
supervisor
opponent
  • Associate professor Wold, Agnes, University of Gothenburg
organization
publishing date
type
Thesis
publication status
published
subject
keywords
transplantation, Immunology, serology, pyocyanin, mannan binding lectin, Pseudomonas aeruginosa, ANCA, Cystic fibrosis, bactericidal/permeability increasing protein, Immunologi, serologi
pages
108 pages
publisher
Lund University
defense location
Segerfalksalen, Wallenberg Neurocentrum, BMC, Lund
defense date
2007-03-02 09:00
ISSN
1652-8220
ISBN
978-91-85559-06-0
language
English
LU publication?
yes
id
d3700d70-95ea-458f-9d11-a3245cd2d05a (old id 548062)
date added to LUP
2007-09-10 14:29:19
date last changed
2016-09-19 08:44:58
@phdthesis{d3700d70-95ea-458f-9d11-a3245cd2d05a,
  abstract     = {In cystic fibrosis (CF) colonization of the airways with Pseudomonas aeruginosa is a major cause of deterioration and death. Host defence fails to clear the invading bacteria, which results in a chronic destructive inflammatory process. This thesis deals with factors in the interaction between bacteria and host defence that determine the extent of tissue damage caused by the bacteria.<br/><br>
<br/><br>
(I) Autoantibodies against bactericidal/permeability increasing protein (BPI-ANCA) were measured in 46 CF patients and were found in a prevalence of 72 %. We found a strong correlation between BPI-ANCA concentration and lung damage, especially in P. aeruginosa colonized patients.<br/><br>
<br/><br>
(II) Precence of BPI-ANCA was found to predict severe adverse outcome in the 46 adult patients after 5-7 years. BPI-ANCA was measured in 366 patients. The patients were followed prospectively and we found that the BPI-ANCA response occurred following colonization with P. aeruginosa. In all patients who were lung transplanted, the BPI-ANCA levels decreased. In patients who were colonized with P. aeruginosa and had no BPI-ANCA, median lung function was normal.<br/><br>
<br/><br>
(III) Binding of mannan-binding lectin (MBL) may activate complement. About 10% of the population are MBL-deficient. When investigating 114 CF patients we found no correlation between MBL pathway deficiencies and severe lung disease. The levels of MBL in serum were found to be higher in CF patients than in controls.<br/><br>
<br/><br>
(IV) Isolates of P.aeruginosa from CF patients were collected and their interactions with human cells were investigated. We found that isolates from patients with positive BPI-ANCA had white phenotypes and evoked mild inflammatory responses.<br/><br>
<br/><br>
Conclusions: We suggest that P. aeruginosa is a risk factor for severe lung damage in CF particularly if accompanied by a rise in BPI-ANCA in serum. The BPI-ANCA response was secondary to colonization with P. aeruginosa, BPI-ANCA associated strains of P. aeruginosa evoked a mild inflammatory response. We speculate that inadequate inflammation impairs host defence, and thus allows bacterial proliferation, which apparently is a disadvantage to the host. MBL-deficiency was not a risk factor for severe lung disease in the studied cohort.},
  author       = {Carlsson, Malin},
  isbn         = {978-91-85559-06-0},
  issn         = {1652-8220},
  keyword      = {transplantation,Immunology,serology,pyocyanin,mannan binding lectin,Pseudomonas aeruginosa,ANCA,Cystic fibrosis,bactericidal/permeability increasing protein,Immunologi,serologi},
  language     = {eng},
  pages        = {108},
  publisher    = {Lund University},
  school       = {Lund University},
  title        = {Immunological aspects on cystic fibrosis lung disease},
  year         = {2007},
}