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Reduced corticosteroid‐binding globulin cleavage in active rheumatoid arthritis
Author(s) -
Nenke Marni A.,
Lewis John G.,
Rankin Wayne,
McWilliams Leah,
Metcalf Robert G.,
Proudman Susanna M.,
Torpy David J.
Publication year - 2016
Publication title -
clinical endocrinology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.055
H-Index - 147
eISSN - 1365-2265
pISSN - 0300-0664
DOI - 10.1111/cen.13081
Subject(s) - transcortin , medicine , endocrinology , rheumatoid arthritis , rheumatology , glucocorticoid , globulin , glucocorticoid receptor , hydrocortisone , immunology
Summary Objective Corticosteroid‐binding globulin ( CBG ), the cortisol transport protein, is cleaved from high‐affinity (ha CBG ) to low‐affinity (la CBG ) 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 , ha CBG and la CBG , 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 ( DAS 28: range 1·2–6·4). la CBG 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 ha CBG 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 .