Background:

An anterior cruciate ligament (ACL) rupture results in an increased risk of developing knee osteoarthritis (OA) at an early age. Before clinical signs become apparent, the OA process has already been initiated. Therefore, it is important to look at the cascade of changes, such as the activity of cytokines and proteases, which might be associated with the later development of OA.

Purpose:

To compare biomarker levels in patients with a recent ACL rupture with those in controls with a healthy knee and to monitor biomarker levels over 2 years after an ACL rupture.

Study Design:

Descriptive laboratory study.

Methods:

Patients were enrolled after an ACL tear was identified. Serum and urine samples were collected at the time of enrollment in the study (3-25 weeks after the injury) and then at 14 and 27 months after the injury between January 2009 and November 2010. Reference samples were obtained from participants with healthy knees. The following biomarkers were measured with immunological assays: aggrecan ARGS neoepitope (ARGS-aggrecan), tumor necrosis factor–α (TNF-α), interferon-γ, interleukin (IL)–8, IL-10, IL-13, N-terminal cross-linked telopeptide of type I collagen (NTX-I), and C-terminal cross-linked telopeptide of type II collagen (CTX-II).

Results:

Samples were collected from 152 patients with an acute ACL rupture, who had a median age of 25 years (interquartile range [IQR], 21-32 years). There were 62 urine reference samples (median age, 25 years [IQR, 22-36 years]) and 26 serum reference samples (median age, 35 years [IQR, 24-39 years]). At a median of 11 weeks (IQR, 7-17 weeks) after trauma, serum levels of both ARGS-aggrecan and TNF-α were elevated 1.5-fold (P < .001) compared with reference samples and showed a time-dependent decrease during follow-up. Urine NTX-I and CTX-II concentrations were elevated in an early phase after trauma (1.3-fold [P < .001] and 3.7-fold [P < .001], respectively) compared with reference samples, and CTX-II levels remained elevated compared with reference samples at 2-year follow-up. Strong correlations were found between serum ARGS-aggrecan, urinary NTX-I, and urinary CTX-II (r_s = 0.57-0.68).

Conclusion:

In the first few months after an ACL injury, there was a measurable increase in serum levels of ARGS-aggrecan and TNF-α as well as urine levels of NTX-I and CTX-II. These markers remained high compared with those of controls with healthy knees at 2-year follow-up.

中文翻译：

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前交叉韧带断裂增加了尿液 I 型胶原蛋白 N 端交联端肽、II 型胶原蛋白 C 端交联端肽、血清聚集蛋白聚糖 ARGS 新表位和血清肿瘤坏死因子 -α 的水平

背景：

前交叉韧带 (ACL) 断裂会导致在幼年时患膝骨关节炎 (OA) 的风险增加。在临床症状变得明显之前，OA 过程已经启动。因此，重要的是观察一系列变化，例如细胞因子和蛋白酶的活性，这可能与 OA 的后期发展有关。

目的：

比较近期 ACL 断裂患者与健康膝关节对照组的生物标志物水平，并在 ACL 断裂后 2 年内监测生物标志物水平。

学习规划：

描述性实验室研究。

方法：

患者在发现 ACL 撕裂后入组。在参加研究时（受伤后 3-25 周）以及受伤后 14 和 27 个月（2009 年 1 月至 2010 年 11 月）收集血清和尿液样本。参考样本来自膝关节健康的参与者。使用免疫学分析测量了以下生物标志物：聚集蛋白聚糖 ARGS 新表位 (ARGS-聚集蛋白聚糖)、肿瘤坏死因子-α (TNF-α)、干扰素-γ、白细胞介素 (IL)-8、IL-10、IL-13、N- I型胶原的末端交联端肽（NTX-I）和II型胶原的C-末端交联端肽（CTX-II）。

结果：

样本来自 152 名急性 ACL 断裂患者，他们的中位年龄为 25 岁（四分位距 [IQR]，21-32 岁）。有 62 个尿液参考样本（中位年龄，25 岁​​ [IQR，22-36 岁]）和 26 个血清参考样本（中位年龄，35 岁 [IQR，24-39 岁]）。在创伤后 11 周（IQR，7-17 周）的中位数，ARGS-聚集蛋白聚糖和 TNF-α 的血清水平与参考样本相比升高了 1.5 倍（P < .001），并显示出时间依赖性降低随访期间。尿 NTX-I 和 CTX-II 浓度在创伤后早期升高（1.3 倍 [ P < .001] 和 3.7 倍 [ P< .001]）与参考样本相比，在 2 年的随访中，CTX-II 水平与参考样本相比仍然升高。发现血清 ARGS-蛋白聚糖、尿 NTX-I 和尿 CTX-II 之间存在强相关性 ( r _s = 0.57-0.68)。

结论：

在 ACL 损伤后的最初几个月，ARGS-聚集蛋白聚糖和 TNF-α 的血清水平以及 NTX-I 和 CTX-II 的尿液水平显着升高。在 2 年的随访中，这些标志物与膝关节健康的对照组相比仍然很高。