Biomarkers and phenotype concepts in sarcoidosis care

Abstract

Sarcoidosis is a heterogeneous disease with an unpredictable disease course, which makes clinical management challenging. Better understanding of classic and potential new biomarkers and phenotypes could help clinicians to guide patients with sarcoidosis regarding diagnosing, prognostication, initiation of treatment and its evaluation. This thesis further elucidated the role of existing biomarkers as well as identified new biomarkers in different phenotypes of patients with sarcoidosis in order to improve clinical care in this heterogeneous complex disease. The results in our thesis demonstrated that the serological biomarker soluble interleukin 2 receptor (sIL-2R) is useful for prognostication. However, as diagnostic biomarker sIL-2R is limited due to a low specificity. In bronchoalveolar lave (BAL) fluid, the percentage lymphocytes and the CD4+/CD8+ ratio are useful to predict prognosis. Our findings suggest that a phenotype indicative of favourable disease is characterised by a low lymphocyte percentage and a high CD4+/CD8+ ratio. We have found that the tag single nucleotide polymporphisms (SNPs) for HLA-DRB1*0301 and HLA-DRB1*1501 can be used as genetic markers for prognostication. In addition, we demonstrated that the SNPs tagging HLA-DRB1*0301 and HLA-DRB1*1501 associate with BAL cell characteristics. We also conducted research on radiological markers in sarcoidosis. The presence of a usual interstitial pneumonia (UIP)-like pattern on a high-resolution computed tomography is a predictor of worse outcome. Positron emission tomography is used in sarcoidosis to assess inflammation. The PET-measures maximum standardised uptake value (SUVmax) and total lung glycolysis are equal in determining and predicting lung function response after treatment. Furthermore, this thesis described novel insights in the progressive fibrosing phenotype (PF-ILD) in sarcoidosis. We have demonstrated that PF-ILD is a relatively rare but lethal phenotype in sarcoidosis. PF-ILD, alongside pulmonary hypertension and a UIP-like pattern, has been shown to be a significant predictor of mortality. In addition to our research into biomarkers and phenotypes in sarcoidosis, we conducted research on infliximab biosimilar Inflectra® in patients with refractory sarcoidosis, revealing Inflectra® to be safe and effective as third-line treatment option in sarcoidosis. This thesis provides new perspectives regarding the use of current as well as novel biomarkers in the management of patients with various phenotypes of sarcoidosis. It will hopefully stimulate further research into the role of these biomarkers, helping the field to take another step into personalised medicine in patients with this multifaceted disease.