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Celiac disease and Infections
Örebro University, School of Medical Sciences.ORCID iD: 0000-0001-8126-9738
2019 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Background: Celiac disease (CD) is a chronic immune-mediated enteropathy affecting about 1% of the population worldwide. CD is triggered by ingestion of gluten in genetically predisposed individuals but additional factors (e.g. infections) are required for the disease to develop. CD also seems to be associated with infectious complications.

Aim: The main objective of this thesis was to increase the knowledge about the associations between CD and infections.

Methods: Epidemiological and laboratory approaches. Studies I-III used a data set consisting of small intestinal biopsy reports. The biopsies were taken in 1969-2008 and collected in 2006-2008. A total of 29,096 individuals with CD, 13,306 with inflammation and 3,719 with potential CD were identified. Each individual was matched with up to 5 controls from the general population (n= 228,632). Through linkage of the data to the Patient Register study I examined the risk of hospital visits due to respiratory syncytial virus (RSV) in children <2 years prior to onset of CD. Study II used the Patient Register and Cause of Death Register to assess whether CD affects the outcome in sepsis. Study III linked the data to microbiological data bases and the Public Health Agency to estimate risk of invasive pneumococcal disease (IPD) in CD. In study IV children with CD and controls were recruited from Kalmar County Hospital. Complement activation (C3a and sC5b-9) in plasma were analysed after incubation with pneumococci.

Results: Study I found that children with CD were more likely than controls to have attended hospital due to RSV infection prior to diagnosis (odds ratio 1.46; 95% confidence interval (CI)=1.02-2.07). CD did not seem to influence survival in sepsis (adjusted hazard ratio (HR) 1.10 95%CI=0.72-1.69) (study II). Study III indicated a 46% risk increase for individuals with CD to acquire IPD (HR 1.46; 95%CI=1.05-2.03) but study IV did not reveal any differences in complement response in regard to CD status (p=0.497and p=0.724), explaining this excess risk.

Conclusion: This thesis supports associations between CD and infections preceding and complicating diagnosis. However, CD does not seem to influence the outcome in a severe infection like sepsis and altered complement function is unlikely to be responsible for the excess IPD risk in CD.

Place, publisher, year, edition, pages
Örebro: Örebro University , 2019. , p. 97
Series
Örebro Studies in Medicine, ISSN 1652-4063 ; 188
Keywords [en]
Celiac disease, small intestinal, infection, respiratory syncytial virus, sepsis, streptococcus pneumoniae, complement, cohort, register
National Category
General Practice
Research subject
Medicine
Identifiers
URN: urn:nbn:se:oru:diva-71643ISBN: 978-91-7529-278-6 (print)OAI: oai:DiVA.org:oru-71643DiVA, id: diva2:1281301
Public defence
2019-03-22, Örebro universitet, Campus USÖ, hörsal C1, Södra Grev Rosengatan 32, Örebro, 13:00 (English)
Opponent
Supervisors
Available from: 2019-01-22 Created: 2019-01-22 Last updated: 2019-04-10Bibliographically approved
List of papers
1. Children with celiac disease are more likely to have attended hospital for prior respiratory syncytial virus infection
Open this publication in new window or tab >>Children with celiac disease are more likely to have attended hospital for prior respiratory syncytial virus infection
2014 (English)In: Digestive Diseases and Sciences, ISSN 0163-2116, E-ISSN 1573-2568, Vol. 59, no 7, p. 1502-1508Article in journal (Refereed) Published
Abstract [en]

Background and Aim: The purpose of this study was to examine the association between celiac disease (CD) and prior respiratory syncytial virus (RSV) infection or any viral bronchiolitis.

Methods: This was a retrospective case–control study. During 2006–2008 small intestinal biopsy data were collected from Sweden’s 28 pathology departments. We identified 3,835 children diagnosed with CD (villous atrophy, Marsh stage 3) before the age of 2 years in 1987 or later. Using conditional logistic regression we calculated odds ratios (ORs) for having a prior diagnosis of respiratory syncytial virus or other viral bronchiolitis compared to 19,102 age- and sex-matched controls.

Results: Of the 3,835 children with CD, 36 (0.9 %) had a prior diagnosis of RSV compared to 117/19,102 (0.6 %) matched controls. This corresponded to an OR of 1.46 (95 % CI 1.03–2.07). ORs were similar in girls and boys. The highest ORs were seen in children developing early CD (before 1 year of age (OR 1.82; 95 % CI 0.91–3.62). Prior record of any type of viral bronchiolitis was found in 3.4 % (132/3,835) of individuals with CD and in 2.0 % (390/19,102) of the matched controls corresponding to an OR of 1.60 (95 % CI 1.33–1.92).

Conclusions: Children with CD diagnosed\2 years of age were more likely to have attended hospital for a prior RSV infection or any viral bronchiolitis than other children.

Place, publisher, year, edition, pages
Dordrecht, Netherlands: Springer, 2014
Keywords
Autoimmunity, bronchiolitis, child, coeliac, infant, inflammation, respiratory syncytial virus
National Category
Gastroenterology and Hepatology
Identifiers
urn:nbn:se:oru:diva-44857 (URN)10.1007/s10620-014-3046-1 (DOI)000338344500024 ()24510390 (PubMedID)2-s2.0-84903546143 (Scopus ID)
Funder
Swedish Society of Medicine
Note

Funding Agencies:

Kalmar County Council

Swedish Research Council-Medicine  522-2A09-195

Swedish Celiac Society

Fulbright Commission

Available from: 2015-06-08 Created: 2015-06-08 Last updated: 2019-02-27Bibliographically approved
2. Does celiac disease influence survival in sepsis?: A nationwide longitudinal study
Open this publication in new window or tab >>Does celiac disease influence survival in sepsis?: A nationwide longitudinal study
2016 (English)In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 11, no 4, article id e0154663Article in journal (Refereed) Published
Abstract [en]

Background: Individuals with celiac disease (CD) are at increased risk of sepsis. The aim of this study was to examine whether CD influences survival in sepsis of bacterial origin.

Methods: Nationwide longitudinal registry-based study. Through data on small intestinal biopsies from Sweden's 28 pathology departments, we identified 29,096 individuals with CD (villous atrophy, Marsh stage III). Each individual with CD was matched with five population-based controls. Among these, 5,470 had a record of sepsis according to the Swedish Patient Register (1,432 celiac individuals and 4,038 controls). Finally we retrieved data on mortality in sepsis patients through the Swedish Cause of Death Registry.

Results: CD was associated with a 19% increase in overall mortality after sepsis (95% confidence interval (CI) = 1.09-1.29), with the highest relative risk occurring in children (adjusted hazard ratio (aHR) = 1.62; 95%CI = 0.67-3.91). However, aHR for death from sepsis was lower (aHR = 1.10) and failed to reach statistical significance (95%CI = 0.72-1.69). CD did not influence survival within 28 days after sepsis (aHR = 0.98; 95%CI = 0.80-1.19).

Conclusions: Although individuals with CD seem to be at an increased risk of overall death after sepsis, that excess risk does not differ from the general excess mortality previously seen in celiac patients in Sweden. CD as such does not seem to influence short-term or sepsis-specific survival in individuals with sepsis and therefore is not an independent risk factor for poor prognosis in sepsis.

Place, publisher, year, edition, pages
San Francisco, USA: Public Library of Science, 2016
National Category
Immunology
Identifiers
urn:nbn:se:oru:diva-50105 (URN)10.1371/journal.pone.0154663 (DOI)000375211700121 ()27124735 (PubMedID)2-s2.0-84964859397 (Scopus ID)
Funder
Swedish Research Council
Note

Funding Agency:

Kalmar County Council

Available from: 2016-05-03 Created: 2016-05-03 Last updated: 2019-03-22Bibliographically approved
3. Coeliac disease and invasive pneumococcal disease: a population-based cohort study
Open this publication in new window or tab >>Coeliac disease and invasive pneumococcal disease: a population-based cohort study
Show others...
2017 (English)In: Epidemiology and Infection, ISSN 0950-2688, E-ISSN 1469-4409, Vol. 145, no 6, p. 1203-1209Article in journal (Refereed) Published
Abstract [en]

Severe infections are recognized complications of coeliac disease (CD). In the present study we aimed to examine whether individuals with CD are at increased risk of invasive pneumococcal disease (IPD). To do so, we performed a population-based cohort study including 29 012 individuals with biopsy-proven CD identified through biopsy reports from all pathology departments in Sweden. Each individual with CD was matched with up to five controls (n = 144 257). IPD events were identified through regional and national microbiological databases, including the National Surveillance System for Infectious Diseases. We used Cox regression analyses to estimate hazard ratios (HRs) for diagnosed IPD. A total of 207 individuals had a record of IPD whereas 45/29 012 had CD (0.15%) and 162/144 257 were controls (0.11%). This corresponded to a 46% increased risk for IPD [HR 1.46, 95% confidence interval (CI) 1.05-2.03]. The risk estimate was similar after adjustment for socioeconomic status, educational level and comorbidities, but then failed to attain statistical significance (adjusted HR 1.40, 95% CI 0.99-1.97). Nonetheless, our study shows a trend towards an increased risk for IPD in CD patients. The findings support results seen in earlier research and taking that into consideration individuals with CD may be considered for pneumococcal vaccination.

Place, publisher, year, edition, pages
Cambridge University Press, 2017
Keywords
Coeliac disease, pneumococcal infection, pneumococci, septicaemia
National Category
Public Health, Global Health, Social Medicine and Epidemiology Infectious Medicine
Identifiers
urn:nbn:se:oru:diva-57618 (URN)10.1017/S0950268816003204 (DOI)000398972000012 ()2-s2.0-85010858898 (Scopus ID)
Funder
The Swedish Medical AssociationSwedish Research Council
Note

Funding Agencies:

Public Health Agency of Sweden  

Kalmar County Council  

Swedish Coeliac Society  

Stockholm County Council 

Available from: 2017-05-10 Created: 2017-05-10 Last updated: 2019-02-27Bibliographically approved
4. Celiac disease and complement activation in response to Streptococcus pneumoniae
Open this publication in new window or tab >>Celiac disease and complement activation in response to Streptococcus pneumoniae
Show others...
(English)Manuscript (preprint) (Other academic)
National Category
General Practice
Identifiers
urn:nbn:se:oru:diva-72810 (URN)
Available from: 2019-02-26 Created: 2019-02-26 Last updated: 2019-02-27Bibliographically approved

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