The systemic vasculitides are a group of otherwise diverse diseases that share the characteristic of inflammatory destruction of blood vessels, with high risk of organ damage or death if untreated. With aggressive immune-suppressive treatment, most patients survive, but subsequent disease course is variable, relapse is common, and long-term morbidity from vasculitis or its treatment is expected. There is a significant need for markers of disease activity, risk of relapse, and long-term damage. For most of the vasculitides, pathophysiology is poorly understood. Thus, biological specimens can and should also be studied to identify disease-specific features, such as autoantibodies or novel microbes. The discovery of ANCA antibodies two decades ago shows the great value that such investigations can have in improving diagnostic testing and developing new treatments. The VCRC Longitudinal Studies (see Project 1 of this overall application) include collection of biological specimens at every clinical visit, so that a large repository has been created. The value of the VCRC Biospecimen Repository is evident from the interest that both VCRC and non-VCRC investigators have expressed in performing studies using this resource.
The Specific Aims of this project are to: 1) continue and expand the VCRC Biomarker Discovery Program to identify novel markers of disease activity, response to treatment, and predictors of remission and relapse, in seven forms of vasculitis;2) continue to encourage investigators inside and outside the VCRC to perform studies using VCRC clinical data and biospecimens, using well-established and streamlined procedures for review and approval of proposals and for selection and delivery of samples. 3) expand the sample collection protocol of the VCRC Longitudinal Studies to include collection of whole blood RNA and peripheral blood mononuclear cells in selected patients, to create additional opportunities to discover biomarkers, including novel microbes that may be associated with particular vasculitides or with vasculitis disease activity.

Public Health Relevance

The Vasculitis Clinical Research Consortium (VCRC) is an extensive infrastructure that allows for experts in multiple centers to collaborate on research in vasculitis, a group of rare and serious diseases that feature inflammatory destruction of blood vessels. There is a need for improved blood and urine tests (

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Specialized Center--Cooperative Agreements (U54)
Project #
2U54AR057319-12
Application #
8909279
Study Section
Special Emphasis Panel (ZTR1-CI-8 (01))
Program Officer
Wang, Yan Z
Project Start
2014-09-01
Project End
2019-08-31
Budget Start
2014-09-01
Budget End
2015-08-31
Support Year
12
Fiscal Year
2014
Total Cost
$118,206
Indirect Cost
$13,429
Name
University of Pennsylvania
Department
Type
DUNS #
042250712
City
Philadelphia
State
PA
Country
United States
Zip Code
19104
Bingham 3rd, Clifton O; Bartlett, Susan J; Merkel, Peter A et al. (2016) Using patient-reported outcomes and PROMIS in research and clinical applications: experiences from the PCORI pilot projects. Qual Life Res 25:2109-16
Kermani, Tanaz A; Cuthbertson, David; Carette, Simon et al. (2016) The Birmingham Vasculitis Activity Score as a Measure of Disease Activity in Patients with Giant Cell Arteritis. J Rheumatol 43:1078-84
Sy, Alice; Khalidi, Nader; Dehghan, Natasha et al. (2016) Vasculitis in patients with inflammatory bowel diseases: A study of 32 patients and systematic review of the literature. Semin Arthritis Rheum 45:475-82
Merkel, Peter A; Manion, Michele; Gopal-Srivastava, Rashmi et al. (2016) The partnership of patient advocacy groups and clinical investigators in the rare diseases clinical research network. Orphanet J Rare Dis 11:66
Tamura, Roy N; Krischer, Jeffrey P; Pagnoux, Christian et al. (2016) A small n sequential multiple assignment randomized trial design for use in rare disease research. Contemp Clin Trials 46:48-51
Pagnoux, C; Carette, S; Khalidi, N A et al. (2015) Comparability of patients with ANCA-associated vasculitis enrolled in clinical trials or in observational cohorts. Clin Exp Rheumatol 33:S-77-83
Kermani, Tanaz A; Warrington, Kenneth J; Cuthbertson, David et al. (2015) Disease Relapses among Patients with Giant Cell Arteritis: A Prospective, Longitudinal Cohort Study. J Rheumatol 42:1213-7
Hatemi, Gulen; Ozguler, Yesim; Direskeneli, Haner et al. (2015) Current Status, Goals, and Research Agenda for Outcome Measures Development in Behçet Syndrome: Report from OMERACT 2014. J Rheumatol 42:2436-41
Aydin, Sibel Zehra; Direskeneli, Haner; Sreih, Antoine et al. (2015) Update on Outcome Measure Development for Large Vessel Vasculitis: Report from OMERACT 12. J Rheumatol 42:2465-9
Dejaco, Christian; Oppl, Bastian; Monach, Paul et al. (2015) Serum biomarkers in patients with relapsing eosinophilic granulomatosis with polyangiitis (Churg-Strauss). PLoS One 10:e0121737

Showing the most recent 10 out of 59 publications