Celiac Disease and Infections

Celiac Disease and Infections

Anna Röckert Tjernberg

Akademisk avhandling

Avhandling för medicine doktorsexamen i medicinsk vetenskap, som kommer att försvaras offentligt

fredagen den 22 mars 2019 kl. 13.00, Hörsal C1, Campus USÖ, Örebro Universitet

Opponent: Professor Carolina Ciacci Universitet i Salerno

Salerno, Italien

Örebro universitet

Institutionen för Medicinska vetenskaper Campus USÖ

Abstract

Anna Röckert Tjernberg (2019): Celiac Disease and Infections. Örebro Studies in Medicine 188.

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 ge-netically predisposed individuals but additional factors (e.g. infections) are required for the disease to develop. CD also seems to be associated with infectious complica-tions.

Aim: The main objective of this thesis was to increase the knowledge about the

asso-ciations 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 in-flammation 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% con-fidence interval (CI)=1.02-2.07). CD did not seem to influence survival in sepsis (ad-justed 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 respon-sible for the excess IPD risk in CD.

Keywords: celiac disease, small intestinal, infection, respiratory syncytial virus, sepsis, streptococcus pneumoniae, complement, cohort, register

Anna Röckert Tjernberg, School of Medical Sciences