Immunological aspects on cystic fibrosis lung disease

Malin Carlsson

Immunological aspects on cystic fibrosis lung disease

Malin Carlsson

Nephrology

Research output: Thesis › Doctoral Thesis (compilation)

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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 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.

Original language	English
Qualification	Doctor
Awarding Institution	Division of Microbiology, Immunology and Glycobiology - MIG
Supervisors/Advisors	Segelmark, Mårten, Supervisor
Award date	2007 Mar 2
Publisher	Lund University
ISBN (Print)	978-91-85559-06-0
Publication status	Published - 2007

Bibliographical note

Defence details

Date: 2007-03-02
Time: 09:00
Place: Segerfalksalen, Wallenberg Neurocentrum, BMC, Lund

External reviewer(s)

Name: Wold, Agnes
Title: Associate professor
Affiliation: University of Gothenburg

---

<div class="article_info">Malin Carlsson, Leif Eriksson, Inger Erwander, Jörgen Wieslander and Mårten Segelmark. <span class="article_issue_date">2003</span>. <span class="article_title">Pseudomonas-induced lung damage in cystic fibrosis correlates to bactericidal-permeability increasing protein (BPI)-autoantibodies</span> <span class="journal_series_title">Clinical and Experimental Rheumathology</span>, <span class="journal_volume">vol 21</span> <span class="journal_pages">pp S95-S100</span>.</div>
<div class="article_info">Malin Carlsson, Leif Eriksson, Tania Pressler, Ragnhild Kornfält, Lena Mared, Peter Meyer, Allan Wiik, Jörgen Wieslander and Mårten Segelmark. <span class="article_issue_date">2007</span>. <span class="article_title">Autoantibody responses to BPI predict disease severity and outcome in cystic fibrosis</span> <span class="journal_series_title">Journal of Cystic Fibrosis</span>, <span class="journal_distributor">Elsevier</span> (inpress)</div>
<div class="article_info">Malin Carlsson, Anders Sjöholm, Leif Eriksson, Steffen Thiel, Jens C. Jensenius, Mårten Segelmark and Lennart Truedsson. <span class="article_issue_date">2004</span>. <span class="article_title">Deficiency of the mannan-binding lectin pathway of complement and poor outcome in cystic fibrosis: bacterial colonization may be decisive for a relationship</span> <span class="journal_series_title">Clinical and Experimental Immunology</span>, <span class="journal_volume">vol 139</span> <span class="journal_pages">pp 306-313</span>. <span class="journal_distributor">Blackwell</span></div>
<div class="article_info">Malin Carlsson, Ann-Cathrine Petersson, Catarina Andersson, Leif Eriksson, Mårten Segelmark and Thomas Hellmark. <span class="article_issue_date"></span>. <span class="article_title">Pseudomonas aeruginosa in cystic fibrosis: Pyocyanin negative strains are associated with BPI-ANCA and progressive lung disease</span> (manuscript)</div>

Subject classification (UKÄ)

Immunology in the Medical Area (including Cell and Immunotherapy)
Microbiology in the Medical Area

Free keywords

transplantation
Immunology
serology
pyocyanin
mannan binding lectin
Pseudomonas aeruginosa
ANCA
Cystic fibrosis
bactericidal/permeability increasing protein
Immunologi
serologi

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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e_Ram_MCarlsson

Cite this

@phdthesis{d3700d7095ea458f9d11a3245cd2d05a,

title = "Immunological aspects on cystic fibrosis lung disease",

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 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.",

keywords = "transplantation, Immunology, serology, pyocyanin, mannan binding lectin, Pseudomonas aeruginosa, ANCA, Cystic fibrosis, bactericidal/permeability increasing protein, Immunologi, serologi",

author = "Malin Carlsson",

note = "Defence details Date: 2007-03-02 Time: 09:00 Place: Segerfalksalen, Wallenberg Neurocentrum, BMC, Lund External reviewer(s) Name: Wold, Agnes Title: Associate professor Affiliation: University of Gothenburg --- <div class={"}article_info{"}>Malin Carlsson, Leif Eriksson, Inger Erwander, J{\"o}rgen Wieslander and M{\aa}rten Segelmark. <span class={"}article_issue_date{"}>2003</span>. <span class={"}article_title{"}>Pseudomonas-induced lung damage in cystic fibrosis correlates to bactericidal-permeability increasing protein (BPI)-autoantibodies</span> <span class={"}journal_series_title{"}>Clinical and Experimental Rheumathology</span>, <span class={"}journal_volume{"}>vol 21</span> <span class={"}journal_pages{"}>pp S95-S100</span>.</div> <div class={"}article_info{"}>Malin Carlsson, Leif Eriksson, Tania Pressler, Ragnhild Kornf{\"a}lt, Lena Mared, Peter Meyer, Allan Wiik, J{\"o}rgen Wieslander and M{\aa}rten Segelmark. <span class={"}article_issue_date{"}>2007</span>. <span class={"}article_title{"}>Autoantibody responses to BPI predict disease severity and outcome in cystic fibrosis</span> <span class={"}journal_series_title{"}>Journal of Cystic Fibrosis</span>, <span class={"}journal_distributor{"}>Elsevier</span> (inpress)</div> <div class={"}article_info{"}>Malin Carlsson, Anders Sj{\"o}holm, Leif Eriksson, Steffen Thiel, Jens C. Jensenius, M{\aa}rten Segelmark and Lennart Truedsson. <span class={"}article_issue_date{"}>2004</span>. <span class={"}article_title{"}>Deficiency of the mannan-binding lectin pathway of complement and poor outcome in cystic fibrosis: bacterial colonization may be decisive for a relationship</span> <span class={"}journal_series_title{"}>Clinical and Experimental Immunology</span>, <span class={"}journal_volume{"}>vol 139</span> <span class={"}journal_pages{"}>pp 306-313</span>. <span class={"}journal_distributor{"}>Blackwell</span></div> <div class={"}article_info{"}>Malin Carlsson, Ann-Cathrine Petersson, Catarina Andersson, Leif Eriksson, M{\aa}rten Segelmark and Thomas Hellmark. <span class={"}article_issue_date{"}></span>. <span class={"}article_title{"}>Pseudomonas aeruginosa in cystic fibrosis: Pyocyanin negative strains are associated with BPI-ANCA and progressive lung disease</span> (manuscript)</div>",

year = "2007",

language = "English",

isbn = "978-91-85559-06-0",

publisher = "Lund University",

type = "Doctoral Thesis (compilation)",

school = "Division of Microbiology, Immunology and Glycobiology - MIG",

}

TY - THES

T1 - Immunological aspects on cystic fibrosis lung disease

AU - Carlsson, Malin

N1 - Defence details Date: 2007-03-02 Time: 09:00 Place: Segerfalksalen, Wallenberg Neurocentrum, BMC, Lund External reviewer(s) Name: Wold, Agnes Title: Associate professor Affiliation: University of Gothenburg --- <div class="article_info">Malin Carlsson, Leif Eriksson, Inger Erwander, Jörgen Wieslander and Mårten Segelmark. <span class="article_issue_date">2003</span>. <span class="article_title">Pseudomonas-induced lung damage in cystic fibrosis correlates to bactericidal-permeability increasing protein (BPI)-autoantibodies</span> <span class="journal_series_title">Clinical and Experimental Rheumathology</span>, <span class="journal_volume">vol 21</span> <span class="journal_pages">pp S95-S100</span>.</div> <div class="article_info">Malin Carlsson, Leif Eriksson, Tania Pressler, Ragnhild Kornfält, Lena Mared, Peter Meyer, Allan Wiik, Jörgen Wieslander and Mårten Segelmark. <span class="article_issue_date">2007</span>. <span class="article_title">Autoantibody responses to BPI predict disease severity and outcome in cystic fibrosis</span> <span class="journal_series_title">Journal of Cystic Fibrosis</span>, <span class="journal_distributor">Elsevier</span> (inpress)</div> <div class="article_info">Malin Carlsson, Anders Sjöholm, Leif Eriksson, Steffen Thiel, Jens C. Jensenius, Mårten Segelmark and Lennart Truedsson. <span class="article_issue_date">2004</span>. <span class="article_title">Deficiency of the mannan-binding lectin pathway of complement and poor outcome in cystic fibrosis: bacterial colonization may be decisive for a relationship</span> <span class="journal_series_title">Clinical and Experimental Immunology</span>, <span class="journal_volume">vol 139</span> <span class="journal_pages">pp 306-313</span>. <span class="journal_distributor">Blackwell</span></div> <div class="article_info">Malin Carlsson, Ann-Cathrine Petersson, Catarina Andersson, Leif Eriksson, Mårten Segelmark and Thomas Hellmark. <span class="article_issue_date"></span>. <span class="article_title">Pseudomonas aeruginosa in cystic fibrosis: Pyocyanin negative strains are associated with BPI-ANCA and progressive lung disease</span> (manuscript)</div>

PY - 2007

Y1 - 2007

N2 - 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.

AB - 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.

KW - transplantation

KW - Immunology

KW - serology

KW - pyocyanin

KW - mannan binding lectin

KW - Pseudomonas aeruginosa

KW - ANCA

KW - Cystic fibrosis

KW - bactericidal/permeability increasing protein

KW - Immunologi

KW - serologi

M3 - Doctoral Thesis (compilation)

SN - 978-91-85559-06-0

PB - Lund University

ER -

Immunological aspects on cystic fibrosis lung disease

Abstract

Bibliographical note

Subject classification (UKÄ)

Free keywords

UN SDGs

Access to Document

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Cite this