Related Experiment Video
Updated: Mar 15, 2026
11:07
Visualizing and Quantifying Pharmaceutical Compounds within Skin using Coherent Raman Scattering Imaging
Published on: November 24, 2021
3.4K
A Proteome-Derived Longitudinal Pharmacodynamic Biomarker for Diffuse Systemic Sclerosis Skin.
Lisa M Rice1, Julio C Mantero1, Giuseppina Stifano1
1Boston University School of Medicine, Boston, Massachusetts, USA.
The Journal of Investigative Dermatology
|September 19, 2016
Summary
This study identified key serum proteins in diffuse cutaneous systemic sclerosis (dcSSc) that reflect disease severity. Two proteins, ST2 and Spondin-1, can serve as a reliable biomarker for tracking skin disease progression in clinical trials.
Area of Science:
- Immunology
- Proteomics
- Rheumatology
Background:
- Diffuse cutaneous systemic sclerosis (dcSSc) is a severe autoimmune disease characterized by ত্বক fibrosis.
- Current biomarkers for dcSSc lack sensitivity in reflecting disease activity and progression.
- Understanding the serum proteome in dcSSc is crucial for identifying novel diagnostic and therapeutic targets.
Purpose of the Study:
- To systematically investigate alterations in the serum proteome of dcSSc patients.
- To identify differentially expressed proteins correlating with disease severity (modified Rodnan skin score).
- To develop a longitudinal pharmacodynamic biomarker for skin disease extent.
Main Methods:
- SOMAscan aptamer technology was used to analyze serum proteomes from dcSSc patients and controls.
- Differentially expressed proteins were identified and correlated with the modified Rodnan skin score.
- Enzyme-linked immunosorbent assay (ELISA) and linear mixed models were employed to validate potential biomarkers.
- Independent cohorts were used for validation of the developed biomarker model.
Main Results:
- 16% of analyzed serum proteins were differentially regulated in dcSSc patients compared to controls and correlated with disease severity.
- Tumor necrosis factor-α, IFN-γ, transforming growth factor-β, and IL-13 were identified as potential upstream regulators.
- ST2 and Spondin-1 were identified as the best analytes to describe longitudinal changes in the modified Rodnan skin score.
- The biomarker model using ST2 and Spondin-1 was successfully validated in three independent cohorts.
Conclusions:
- This study identified novel serum proteins associated with dcSSc pathogenesis and potential therapeutic targets.
- ST2 and Spondin-1 can be combined to form a robust longitudinal biomarker for assessing skin disease progression in dcSSc.
- This biomarker holds promise for use in clinical trials to monitor treatment efficacy and disease changes over time.
Related Concept Videos
01:29Pharmacogenetic Phenotypes: Alterations in Pharmacokinetics, Drug Targets and Biologic Milieu
93
Genetic variations significantly influence drug response through pharmacokinetics, receptor interactions, and biologic milieu modifications. Pharmacokinetic alterations impact drug metabolism and clearance, affecting efficacy and toxicity. Variants in drug-metabolizing enzymes, such as CYP2C9 and CYP2C19, alter drug activation and elimination. For example, CYP2C9 loss-of-function variants require lower warfarin doses to prevent excessive bleeding, while CYP2C19 variants reduce clopidogrel...
93
01:20Measurement of Bioavailability: Pharmacodynamic Methods
937
Pharmacodynamic methods provide insights into a drug's effects on physiological processes over time and play a crucial role in understanding bioavailability and therapeutic efficacy. These methods can be broadly classified into acute pharmacological and therapeutic response approaches, each with distinct mechanisms and applications.The acute pharmacological response method directly correlates a drug's physiological effects, such as ECG or pupil diameter changes, to its time course in the body.
937