Background Tuberculosis is considered to be a severe complication during biologic therapies in patients with rheumatoid arthritis (RA). Importantly, conventional inflammatory biomarkers such as C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) are often normalized by biologic therapies, particularly by IL-6 blockade, but an alternative biomarker for tuberculosis detection remains to be established. Previously, by proteomic approach using sera from RA patients, we identified leucine-rich alpha-2 glycoprotein (LRG) as a novel disease activity marker for RA. Interestingly, serum LRG levels are also elevated in other immune disorders such as Behcet's disease and inflammatory bowel diseases, suggesting that LRG is a biomarker for inflammation.
Objectives We investigated whether LRG is potentially useful for detecting tuberculosis during biologic therapies.
Methods Serum samples were harvested from tuberculosis patients (n=33) without biologic therapies before and after anti-tuberculosis treatment. Serum LRG levels were determined by ELISA. To recapitulate tuberculosis development during biologic therapies in RA patients, a murine model of mycobacterium (BCG) infection with or without anti-IL-6 receptor antibody treatment was used and sera were harvested for ELISA analysis of murine LRG.
Results In tuberculosis patients before anti-tuberculosis therapy, serum LRG levels were significantly elevated compared to those of healthy controls. In addition, serum LRG were significantly reduced 1 month after therapy and were further reduced 3 months after therapy. As in humans, serum LRG levels were elevated in mice with various inflammatory conditions including collagen-induced arthritis and mycobacterium infection. When mice were treated with anti-IL-6R antibody and were subjected to mycobacterial infection, serum LRG levels in these mice were similarly elevated as those in mice treated with control antibody.
Conclusions Our analysis of tuberculosis patients indicates that LRG can be a novel biomarker for tuberculosis. Our analysis of an experimental model suggests that LRG is useful for detecting mycobacterial infection even in the suppression of IL-6 by biologic therapies, although this must be confirmed in human studies. The measurement of serum LRG may thus be useful for the simultaneous monitoring of arthritis activity and tuberculosis infection.
TRAQ-based proteomic identification of leucine-rich alpha-2 glycoprotein as a novel inflammatory biomarker in autoimmune diseases. Ann Rheum Dis. 2010 Apr;69(4):770-4
Disclosure of Interest None declared