THE OFFICIAL NEWS SOURCE OF ACR CONVERGENCE 2022 • NOVEMBER 10-14



Kristina Clark, MD, MRCP: Blister fluid and plasma in systemic sclerosis

Kristina Clark, MD, MRCP
Kristina Clark, MD, MRCP

Poster presenter: Kristina Clark, MD, MRCP, University College London

Poster title: High-density Proteomic Analysis of Skin Blister Fluid and Plasma in Systemic Sclerosis Identifies Local and Systemic Differences for Key Proteins

Scheduled poster session day and time: Monday, Nov. 9, 9 – 11 a.m. EST

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What is your poster about?

Systemic sclerosis (SSc) is a severe rheumatic disease with high mortality from lung and heart disease, and major non-lethal clinical burden, including fibrosis of the skin. Sampling skin gives a unique opportunity to explore local disease mechanisms and better understand pathogenesis. This traditionally requires a surgical punch biopsy, but blister fluid can also be used to sample local environment non-invasively. Modern high-density proteomic analysis of skin blister fluid gives a unique opportunity to understand proteins in the local environment of the skin and to compare with in the circulating plasma. The analysis provides the opportunity to not only understand the difference in proteins between healthy controls and patients with SSc in the early aspects of the disease, but also the chance to compare these proteins between two environments in the same patients (blister and plasma). Substantially more proteins were identified in dermal blister fluid as being significantly different from healthy controls, thus providing clear evidence that this technique gives detailed information on the local pathologic processes. These proteins included key cytokines IL-7 and OSM, chemokines CCL18 and CCL7, and matricellular proteins osteopontin and CYR61. Key cytokines found elevated in both the plasma and blister fluid of early dcSSc patients include IL-6, MCP-1, and COMP. These proteins are dysregulated in both plasma and blister fluid of patients with SSc and likely reflect more systemic abnormalities rather than the local environment of the skin.

Why did you decide to investigate this topic?

This work is part of a much larger project trying to utilize multidimensional phenotyping to understand early diffuse SSc (dcSSc) in the context of the full scleroderma spectrum (the BIOPSY study). Having a well-characterized cohort of patients with SSc, we felt that work on gene expression in the skin and blood would be complemented by understanding what the differences in actual expressed proteins was between these patient subgroups, as well as between the different biological samples.

What excites you most about your work?

Not only does this work allow us to understand some of the local and systemic differences in large-scale proteomic analysis between interstitial blister fluid and plasma, but it also allows us to better understand altered gene expression between patients with SSc. In such a heterogenous disease, it is extremely exciting to further explore not only the genetic differences, but also the local environment of the skin, and then put that back into the clinical context of the patients to help develop better ways of assessing and treating this difficult disease.

What are you working on next related to this poster? 

Our work now focuses on integrating this work on proteomics, with the gene expression data obtained across the full disease spectrum (early dcSSc, established dcSSc, and limited cutaneous SSc). Next, I will explore the biological pathways and networks that are overexpressed in plasma and/or blister fluid in order to try to further understand the disease processes at both the local and systemic level.