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Type: Journal article
Title: Reduced corticosteroid-binding globulin cleavage in active rheumatoid arthritis
Author: Nenke, M.
Lewis, J.
Rankin, W.
McWilliams, L.
Metcalf, R.
Proudman, S.
Torpy, D.
Citation: Clinical Endocrinology, 2016; 85(3):369-377
Publisher: Wiley
Issue Date: 2016
ISSN: 0300-0664
Statement of
Marni A. Nenke, John G. Lewis, Wayne Rankin, Leah McWilliams, Robert G. Metcalf, Susanna M. Proudman and David J. Torpy
Abstract: Objective: Corticosteroid-binding globulin (CBG), the cortisol transport protein, is cleaved from high-affinity (haCBG) to low-affinity (laCBG) CBG at sites of inflammation releasing bioavailable, anti-inflammatory cortisol. Rheumatoid arthritis (RA) is a glucocorticoid-responsive disorder, with paradoxically normal cortisol levels despite elevated inflammatory mediators. Our objective was to determine whether CBG cleavage relates to RA disease activity. We hypothesized that impaired CBG cleavage may limit delivery of free cortisol to inflamed joints in RA. Design: Prospective, cross-sectional observational study. Setting and Participants: Fifty-three patients with RA recruited from a Rheumatology outpatient clinic at a tertiary referral centre in Adelaide, Australia, and 73 healthy controls. Measurements: Total CBG, haCBG and laCBG, total, free and salivary cortisol, inflammatory markers including interleukin-6 soluble receptor (IL-6sR) and macrophage migration inhibitory factor and clinical measures of disease activity. Results: Among patients with RA, a wide range of disease activity scores was observed (DAS28: range 1·2-6·4). laCBG was lower in patients with RA (mean ± SEM); 153 ± 9, compared with healthy controls; 191 ± 8 nmol/l, P = 0·003. Levels of total and haCBG were higher in patients with more severe RA disease activity. Free and total cortisol, free cortisol:IL-6sR ratio and total cortisol:IL-6sR ratio correlated negatively with disease activity. Conclusions: These results suggest that patients with RA have reduced CBG cleavage compared to healthy controls and that cleavage is reduced further with higher RA disease activity. Hence, impaired CBG-mediated delivery of endogenous cortisol may perpetuate chronic inflammation in RA.
Keywords: Pituitary-Adrenal System
Hypothalamo-Hypophyseal System
Arthritis, Rheumatoid
Receptors, Interleukin-6
Severity of Illness Index
Case-Control Studies
Prospective Studies
Cross-Sectional Studies
Aged, 80 and over
Middle Aged
Rights: © 2016 John Wiley & Sons Ltd
DOI: 10.1111/cen.13081
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