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Judith Thijs

Wednesday 20 September 2017

Biomarkers in atopic dermatitis

Promotor: prof.dr. C.A.F.M. (Carla) Bruijnzeel - Koomen
Supervisor: dr. D.J. (Dirk Jan) Hijnen & dr. S. (Stefan) Nierkens
Date: 20 September 2017
Time: 12.45 h

Summary
Biomarkers for disease severity in atopic dermatitis
A meta-analysis including 222 studies showed that serum TARC level is the best biomarker for disease severity currently available (chapter 2).
Immunoglobulin free light chains have been shown to correlate with disease severity in paediatric AD. However, they do not correlate with disease severity in adult AD (chapter 6).
A pilot study in 17 AD patients showed that a combination of serum biomarkers is better in assessing disease severity than a single biomarker (chapter 3).
In a prospective cohort of 200 patients it was shown that combining serum TARC, IL-22 and sIL-2R levels in an algorithm accurately predicts clinically measured disease severity (predicted EASI) in 90% of AD patient treated with topical steroids (chapter 4).
The p-EASI also predicts disease severity in patients treated with cyclosporin A (chapter 5).
The p-EASI offers an objective outcome measure for disease severity in prospective AD studies (chapter 4 and 5).

Biomarkers enabling precision medicine in atopic dermatitis
High expression levels of circulating inflammatory biomarkers suggest that AD is a systemic disease. Recently described comorbidities may be the result of this systemic inflammation, and emphasize the need for a multidisciplinary approach for optimal management of AD and its comorbidities (chapter 9)
AD is a heterogeneous disease both clinically and biologically. We have identified four clusters of AD patients based on specific serum biomarker profiles, implying that each of these clusters is driven by a distinct underlying pathway and these clusters may represent different endotypes (chapter 7).
UGT1A9 polymorphisms can be used to identify patients with non-responsiveness to mycophenolic acid therapy, thereby showing the potential of pharmacodynamic biomarkers in AD (chapter 8).

Improving practical aspects of biomarker measurement
The biomarkers studied in this thesis are measured in serum. However, multiple other sources for biomarker measurement exist, for instance saliva and dried blood spots (chapter 10).
A disadvantage of the use of serum biomarkers is the need for a venipuncture. TARC levels measured in dried blood spots also highly correlate with disease severity and significantly decrease during effective treatment. Therefore, dried blood spots may offer a simple and minimally invasive method for measurement of biomarkers in AD (chapter 11).

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