All ETDs from UAB

Advisory Committee Chair

Alexander J Szalai

Advisory Committee Members

Scott Barnum

S L Bridges

David Briles

Chander Raman

Document Type

Dissertation

Date of Award

2012

Degree Name by School

Doctor of Philosophy (PhD) Heersink School of Medicine

Abstract

C-reactive protein (CRP) is an acute phase protein that is commonly used to evaluate systemic inflammation level. Blood CRP level also correlates very well with rheumatoid arthritis (RA) disease severity. However, CRP has many biological actions that lead one to suspect that it may be playing a role in the development or pathology of the disease. We have directly addressed whether this is the case by the use of novel mouse models (CRP deficiency or transgenic overexpression). We have shown that CRP positively affects collagen-induced arthritis development and progression. In order to thoroughly address the question, we have also reported a mechanism by which CRP may be exerting its influence on the system, through modulation of dendritic cells, which potently modulate T cell function. We have also shown that this is a split-paradigm; CRP's multiple biological functions and abilities are differentially influential. In line with this, we have shown that lowering CRP level in mice with established arthritis is therapeutic. Overall, we have thoroughly shown that CRP impacts arthritic disease and in doing so have discovered important new facts that will change the way that RA and its management are considered. We have set the stage for further examination of the relationship between CRP and RA and have contributed to the development of a novel therapy.

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