类风湿关节炎合并间质性肺病患者血清中转化生长因子-β骨形成蛋白-4检测及其意义

The significance of serum concentrations of transforming growth factor-β1 and bone morphogeneticprotein-4 in patients with rheumatoid arthritis and interstitial lung disease

目的探讨类风湿关节炎（RA）合并间质性肺病（ILD）患者的临床特点和转化生长因子（TGF）-β1、骨形成蛋白（BMP）-4在血清中的水平。方法入选28例RA-ILD患者、32例单纯RA患者和20名健康对照，RA-ILD组进一步分为早期组（16例）和中晚期组（12例），酶联免疫吸附试验（ELISA）法测定血清中TGF-β1、BMP-4水平，并分析血清TGF-β1、BMP-4水平与实验室指标的相关性。采用t检验、单因素方差分析及Spearman相关分析法进行数据分析。结果与单纯RA患者相比，RA-ILD组患者初次发生关节炎时年龄较大，关节功能优于单纯RA组患者，血清类风湿因子（RF）滴度高（P〈0．05，P〈0．05，P〈0．01），出现肺间质病变时间为2-6年，平均（3．0±1．2）年。TGF-β1水平在RA-ILD组稍增高，但3组相比差异无统计学意义（P〉0．05）。早期RA-ILD组患者TGF-β1血清水平明显增高，与中晚期RA．ILD组及单纯RA组、健康对照组相比较差异均有统计学意义（P＜0．01）。RA-ILD组患者BMP-4水平低于单纯RA组及健康对照组，差异有统计学意义（P〈0．05），且早期RA-ILD组患者BMP-4水平显著下降，与中晚期RA-ILD组及单纯RA组、健康对照组相比较差异均有统计学意义（P〈0．05）。血清BMP-4水平与TGF-β1水平之间无相关性（p〉0．05），血清TGF-β1、BMP-4水平与实验室指标红细胞沉降率、C反应蛋白、RF、抗环瓜氨酸肽（CCP）抗体等均无明显相关性（P均〉O．05）。结论在早期RA-ILD患者中血清TGF-β1水平增高，BMP-4水平减低，二者可能参与了RA患者ILD的发生。

Objective To compare the serum levels of transforming growth factor （TGF）-beta 1, bone morphogenetic protein （BMP）-4 in patients with rheumatoid arthritis （RA） and RA with interstitial lung disease （RA-ILD）. Methods Twenty-eight RA-ILD patients, 32 patients with RA but without ILD and 20 normal controls were enrolled. The RA-ILD group was further divided into early group and late group. All the observed subjects were analyzed using enzyme linked immunosorbent assay （ELISA） for the determination of serum TGF-β1 and BMP-4 levels. The relationship between the serum levels of TGF-β1, BMP-4 and laboratory examinations were investigated. Comparisions between groups were tested by one-way ANOVA analysis and ttest. Correlation of indexs were observed by Spearman method. Results Patients in the RA-ILD group were older than RA group in disease onset age, in addition, patients with ILD had better joint function and higher serum rheumatoid factor titers. The occurrence time of interstitial lung disease was 2-6 years after the onset of arthritis, with an average time of （3.0±1.2） years. The TGF-β1 levels in the RA-ILD group were slightly higher, but not statistically significant than other groups （P〉0.05）. The TGF-β1 serum levels in the early RA-ILD patients were significantly increased than those of the late RA-ILD group and the RA group. BMP-4 levels in patients with RA-ILD group were less than RA without ILD group and healthy control group, and the differ- ence was statistically significant （P〈0.05）. BMP-4 level in early RA-ILD group was significantly decreased than those of the late RA-ILD group and RA group. No correlation between the serum BMP-4, TGF-β1 level （P〉0.05） no assay result correlated with laboratory parameters including ESR, CRP, RF and anti-CCPantibodies （P〉0.05）. Conclusion TGF-β1 serum levels are increased and BMP-4 levels are decreased in early RA-ILD patients. The serum levels of TGF-β1 and BMP-4 may be indicatior for asymptomatic ILD and reflect disease progression.