Systemic sclerosis (SSc; scleroderma) is a chronic multisystem autoimmune disease that includes prominent skin involvement in all patients and is characterized by fibrosis, inflammation, and microvascular injury of the skin and internal organs. Clinical trial design for patients with systemic sclerosis (SSc) has been confounded by the heterogeneity of disease progression and lack of objective outcome measures. This has hampered identification of therapies for patients who have frequently fatal fibrotic complications. Direct pulmonary complications are the leading cause of death in SSc. For clinical trials in patients with diffuse cutaneous SSc, identification of a pharmacodynamic biomarker associated with clinical improvement would allow for alternative approaches to trial design. Furthermore, identification of a diagnostic biomarker for SSc complicated by pulmonary arterial hypertension (SSc-PAH) would provide a reliable non-invasive method for diagnosis of pulmonary arterial hypertension.
Through the combination of high throughput technologies and clinical information we have identified three preliminary biomarkers for SSc: i) Two pharmacodynamic biomarkers for diffuse skin disease (dcSSc), one in using mRNA from skin biopsies and one using proteomic profiles from sera; ii) a serum based proteomic classifier for the screening and diagnostic evaluation of pulmonary arterial hypertension in systemic sclerosis.
We show these biomarkers can be applied to assess changes in skin disease in dSSc patients over time and with further development could be used to supplement or replace the physical examination assessment (Modified Rodnan Skin Score, MRSS) as an outcome measure in clinical trials for dcSSc patients. Routine use of these biomarkers in SSc clinical trial design could expand treatment options for a patient population that currently has few if any treatment options that slow progression of disease.
Furthermore we identified a serum biomarker for the major SSc pulmonary complication, SSc-PAH. This diagnostic SSc-PAH biomarker has the potential to be used as a screening tool in order to reduce the need for unnecessary invasive diagnostic procedures. This non-invasive screening method could lead to early diagnosis thus improving patient survival and aid in clinical management of a complication for which there are several treatments but which is still frequently fatal. / 2018-06-15T00:00:00Z
| Identifer | oai:union.ndltd.org:bu.edu/oai:open.bu.edu:2144/16736 |
| Date | 15 June 2016 |
| Creators | Rice, Lisa |
| Source Sets | Boston University |
| Language | en_US |
| Detected Language | English |
| Type | Thesis/Dissertation |
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