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Predictors and early biomarkers in Giant Cell Arteritis

Wadström, Karin LU (2022) In Lund University, Faculty of Medicine Doctoral Dissertation Series
Abstract
Abstract
Giant Cell Arteritis (GCA) is the most common vasculitis in adults among people in the western world. The pathogenesis and etiology are not fully understood.
In Study I, we investigated potential predictors for developing GCA, i.e. Body Mass Index (BMI), smoking and hormone-related factors, in a nested case control study. We identified cases and matched controls (4/case) who previously had participated in two health surveys performed in Malmö, Sweden, between 1974 and 1996, the Malmö Preventive Medicine Program (MPMP) and the Malmö Diet and Cancer Study (MDCS). We found a significant association between a higher BMI and reduced risk of subsequent development of GCA (Odds ratio 0.91 per kg/m2; 95 % confidence interval... (More)
Abstract
Giant Cell Arteritis (GCA) is the most common vasculitis in adults among people in the western world. The pathogenesis and etiology are not fully understood.
In Study I, we investigated potential predictors for developing GCA, i.e. Body Mass Index (BMI), smoking and hormone-related factors, in a nested case control study. We identified cases and matched controls (4/case) who previously had participated in two health surveys performed in Malmö, Sweden, between 1974 and 1996, the Malmö Preventive Medicine Program (MPMP) and the Malmö Diet and Cancer Study (MDCS). We found a significant association between a higher BMI and reduced risk of subsequent development of GCA (Odds ratio 0.91 per kg/m2; 95 % confidence interval 0.84-0.98).
In Study II the objective was to investigate how duration of glucocorticosteroid treatment affects TAB findings. Previous studies have shown conflicting results regarding the effect of treatment prior to biopsy. We found that biopsies taken 1-4 weeks after initiating of treatment still yield clinically useful information for the diagnosis of GCA.
Study III aimed to investigate the role of metabolic factors as predictors of GCA. Validated cases from the MPMP cohort were compared with matched controls. We found that cases had significantly lower fasting blood glucose, total cholesterol levels and triglyceride levels a median of 20.7 years before diagnosis of GCA compared to controls.
In Study IV we investigated the relation between inflammatory biomarkers and subsequent development of GCA. With cases and controls from the MDCS cohort and a median time from screening to diagnosis at 11.9 years. Our results showed that IFN-γ levels were elevated years before onset of GCA, in particular among those sampled closer to diagnosis. In addition, several other T-cell related proteins were also elevated prior to diagnosis, suggesting that activation of the adaptive immune system may precede the clinical onset of GCA.
In conclusion a lower BMI and better metabolic control were identified as predictors of GCA. Our results suggest that features of cellular inflammation may be detected years before disease onset. TABs seem to yield useful information when taken 1-4 weeks after treatment initiation with glucocorticoids. (Less)
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author
supervisor
opponent
  • Associate Professor Mackie, Sarah L., Vascular Rheumatology at University of Leeds. Honorary Consultant Rheumatologist at Leeds Teaching Hospital NHS Trust
organization
publishing date
type
Thesis
publication status
published
subject
keywords
Giant Cell Arteritis, Epidemiology, Biomarkers
in
Lund University, Faculty of Medicine Doctoral Dissertation Series
issue
2022:34
pages
108 pages
publisher
Lund University, Faculty of Medicine
defense location
Reumatologiska klinikens föreläsningssal, Lottasalen, Universitetssjukhuset i Lund. Join by Zoom: https://lu-se.zoom.us/j/63962880631
defense date
2022-03-18 09:00:00
ISSN
1652-8220
ISBN
978-91-8021-195-6
language
English
LU publication?
yes
id
a82c4355-7d3f-402c-9804-bb706093c081
date added to LUP
2022-02-24 12:46:53
date last changed
2022-03-01 11:28:50
@phdthesis{a82c4355-7d3f-402c-9804-bb706093c081,
  abstract     = {{Abstract<br/>Giant Cell Arteritis (GCA) is the most common vasculitis in adults among people in the western world. The pathogenesis and etiology are not fully understood.<br/>In Study I, we investigated potential predictors for developing GCA, i.e. Body Mass Index (BMI), smoking and hormone-related factors, in a nested case control study. We identified cases and matched controls (4/case) who previously had participated in two health surveys performed in Malmö, Sweden, between 1974 and 1996, the Malmö Preventive Medicine Program (MPMP) and the Malmö Diet and Cancer Study (MDCS). We found a significant association between a higher BMI and reduced risk of subsequent development of GCA (Odds ratio 0.91 per kg/m2; 95 % confidence interval 0.84-0.98).<br/>In Study II the objective was to investigate how duration of glucocorticosteroid treatment affects TAB findings. Previous studies have shown conflicting results regarding the effect of treatment prior to biopsy. We found that biopsies taken 1-4 weeks after initiating of treatment still yield clinically useful information for the diagnosis of GCA.<br/>Study III aimed to investigate the role of metabolic factors as predictors of GCA. Validated cases from the MPMP cohort were compared with matched controls. We found that cases had significantly lower fasting blood glucose, total cholesterol levels and triglyceride levels a median of 20.7 years before diagnosis of GCA compared to controls.<br/>In Study IV we investigated the relation between inflammatory biomarkers and subsequent development of GCA. With cases and controls from the MDCS cohort and a median time from screening to diagnosis at 11.9 years. Our results showed that IFN-γ levels were elevated years before onset of GCA, in particular among those sampled closer to diagnosis. In addition, several other T-cell related proteins were also elevated prior to diagnosis, suggesting that activation of the adaptive immune system may precede the clinical onset of GCA.<br/>In conclusion a lower BMI and better metabolic control were identified as predictors of GCA. Our results suggest that features of cellular inflammation may be detected years before disease onset. TABs seem to yield useful information when taken 1-4 weeks after treatment initiation with glucocorticoids.}},
  author       = {{Wadström, Karin}},
  isbn         = {{978-91-8021-195-6}},
  issn         = {{1652-8220}},
  keywords     = {{Giant Cell Arteritis; Epidemiology; Biomarkers}},
  language     = {{eng}},
  number       = {{2022:34}},
  publisher    = {{Lund University, Faculty of Medicine}},
  school       = {{Lund University}},
  series       = {{Lund University, Faculty of Medicine Doctoral Dissertation Series}},
  title        = {{Predictors and early biomarkers in Giant Cell Arteritis}},
  url          = {{https://lup.lub.lu.se/search/files/114533393/ThesisKarinWadstr_m.pdf}},
  year         = {{2022}},
}