Pedersen Susanne Juhl, Sørensen Inge Juul, Lambert Robert G W, Hermann Kay-Geert A, Garnero Patrick, Johansen Julia Sidenius, Madsen Ole Rintek, Hansen Annette, Hansen Michael Sejer, Thamsborg Gorm, Andersen Lis Smedegaard, Majgaard Ole, Loft Anne Gitte, Erlendsson Jon, Asmussen Karsten H, Jurik Anne Grethe, Møller Jakob, Hasselquist Maria, Mikkelsen Dorrit, Østergaard Mikkel
Department of Rheumatology C Post 535, Gentofte University Hospital, Copenhagen, Denmark.
Arthritis Rheum. 2011 Dec;63(12):3789-800. doi: 10.1002/art.30627.
To investigate the relationship of circulating biomarkers of inflammation (C-reactive protein [CRP], interleukin-6 [IL-6], and YKL-40), angiogenesis (vascular endothelial growth factor), cartilage turnover (C-terminal crosslinking telopeptide of type II collagen [CTX-II], total aggrecan, matrix metalloproteinase 3 [MMP-3], and cartilage oligomeric matrix protein [COMP]), and bone turnover (CTX-I and osteocalcin) to inflammation on magnetic resonance imaging (MRI) and radiographic progression in patients with axial spondylarthritis (SpA) beginning tumor necrosis factor α (TNFα) inhibitor therapy.
MRIs were evaluated according to the Berlin sacroiliac (SI) joint and spine inflammation scoring method at baseline, week 22, and week 46. Radiographs were evaluated using the modified Stoke Ankylosing Spondylitis Spine Score at baseline and week 46. Patients with new syndesmophytes were identified. Biomarker levels in patients were compared to levels in healthy subjects.
Higher pretreatment MRI inflammation scores for SI joints and/or lumbar spine were associated with higher baseline CTX-II levels, but not with higher levels of biomarkers of inflammation and bone turnover. During treatment with TNFα inhibitors, a decrease in MRI inflammation scores from baseline to week 22 was associated with larger percentage decreases in and a normalization of CRP and IL-6 levels as compared to an increase or no change in MRI scores. Development of new syndesmophytes was associated with larger percentage decreases in CRP and IL-6 levels and an increase in osteocalcin level, and with normalization of CRP and IL-6 levels from baseline to week 22. Persistent systemic inflammation was associated with radiographic nonprogression.
Our findings indicate that inflammation on baseline MRI is associated with higher CTX-II levels. Radiographic progression is associated with decreased systemic inflammation, as assessed by IL-6 and CRP levels and MRI, supporting the notion of a link between the resolution of inflammation and new bone formation in SpA patients during anti-TNFα therapy.
研究炎症循环生物标志物（C反应蛋白[CRP]、白细胞介素-6[IL-6]和YKL-40）、血管生成（血管内皮生长因子）、软骨周转（II型胶原C端交联末肽[CTX-II]、总聚集蛋白聚糖、基质金属蛋白酶3[MMP-3]和软骨寡聚基质蛋白[COMP]）以及骨周转（CTX-I和骨钙素）与开始肿瘤坏死因子α（TNFα）抑制剂治疗的中轴型脊柱关节炎（SpA）患者磁共振成像（MRI）炎症及放射学进展之间的关系。
根据柏林骶髂关节和脊柱炎症评分方法在基线、第22周和第46周对MRI进行评估。使用改良的斯托克强直性脊柱炎脊柱评分在基线和第46周对X线片进行评估。确定有新骨桥形成的患者。将患者的生物标志物水平与健康受试者的水平进行比较。
骶髂关节和/或腰椎较高的治疗前MRI炎症评分与较高的基线CTX-II水平相关，但与炎症和骨周转生物标志物的较高水平无关。在TNFα抑制剂治疗期间，与MRI评分增加或无变化相比，从基线到第22周MRI炎症评分降低与CRP和IL-6水平更大百分比的降低及恢复正常相关。新骨桥形成与CRP和IL-6水平更大百分比的降低及骨钙素水平升高相关，且与从基线到第22周CRP和IL-6水平恢复正常相关。持续性全身炎症与放射学无进展相关。
我们的研究结果表明，基线MRI炎症与较高的CTX-II水平相关。放射学进展与全身炎症减轻相关，通过IL-6和CRP水平及MRI评估，支持炎症消退与SpA患者抗TNFα治疗期间新骨形成之间存在联系的观点。
