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Brief Report: Leucine‐Rich α 2 ‐Glycoprotein as a Potential Biomarker for Joint Inflammation During Anti–Interleukin‐6 Biologic Therapy in Rheumatoid Arthritis
Author(s) -
Fujimoto Minoru,
Serada Satoshi,
Suzuki Katsuya,
Nishikawa Ayumi,
Ogata Atsushi,
Nanki Toshihiro,
Hattori Kunihiro,
Kohsaka Hitoshi,
Miyasaka Nobuyuki,
Takeuchi Tsutomu,
Naka Tetsuji
Publication year - 2015
Publication title -
arthritis and rheumatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.106
H-Index - 314
eISSN - 2326-5205
pISSN - 2326-5191
DOI - 10.1002/art.39164
Subject(s) - tocilizumab , medicine , rheumatoid arthritis , biomarker , erythrocyte sedimentation rate , arthritis , immunology , inflammation , interleukin 6 , gastroenterology , biology , biochemistry
Objective To investigate whether leucine‐rich α 2 ‐glycoprotein (LRG) could be a biomarker for disease activity during interleukin‐6 (IL‐6) blockade treatment of rheumatoid arthritis (RA). Methods In 59 RA patients who were treated with tocilizumab for 24 weeks, serum LRG levels were determined by enzyme‐linked immunosorbent assay. RA disease activity was evaluated by the Clinical Disease Activity Index (CDAI). Receiver operating characteristic (ROC) curve analysis was used to examine the diagnostic performance of LRG and other biomarkers. In monkeys with experimental autoimmune arthritis, swollen joint counts, joint pathologic changes, and blood levels of C‐reactive protein (CRP) and LRG were evaluated after treatment with anti–IL‐6 receptor antibody. Results Among tocilizumab‐treated RA patients, those with active disease (CDAI >2.8) had significantly higher serum LRG levels compared to those whose disease was in remission. ROC curve analysis suggested that the LRG level was more useful than the CRP or matrix metalloproteinase 3 level or the erythrocyte sedimentation rate in discriminating between remission and active disease during therapy with tocilizumab. In monkeys treated with IL‐6 blockade, joint scores were more closely correlated with LRG levels than with CRP levels. Histologic analysis of joints revealed that LRG levels correlated significantly with granulomatous tissue formation, cartilage degeneration, and bone destruction in IL‐6 blockade–treated monkeys with low levels of CRP. Conclusion Under conditions of IL‐6 inhibition, LRG was more useful than other biomarkers in discriminating between active and inactive disease in human RA and in detecting joint inflammation in experimental arthritis. LRG may serve as a convenient biomarker for RA disease activity during IL‐6 blockade treatment.