可溶性Axl和Tyro3受体酪氨酸激酶在系统性红斑狼疮中的临床意义

The clinical significance of soluble Axl and Tyro3 receptor tyrosine kinase in systemic lupus erythematosus

目的探讨可溶性Axl受体酪氨酸激酶（sAxlTK）和可溶性Tyro3受体酪氨酸激酶（sTyro3TK）在SLE患者血清中的表达情况及临床意义。方法采用ELISA法分别检测140例SLE患者、150例疾病对照组患者及100名健康对照组血清中sAxlTK和sTyr03TK的浓度，并分析与SLE患者临床表现、实验室指标及疾病活动度之间的相关性。采用单因素方差分析，Dunnett’s t检验、x2检验、Spearman相关分析法进行统计学数据分析。结果SLE患者血清中sAxITK[（56±18）ng／ml]和sTyro3TK[（3．9±1．6）ng/ml]水平明显高于疾病对照组患者[sAxlTK：（41±17）ng／ml；sTyro3TK：（2．6±1．2）ng／ml]和健康对照组[sAxlTK：（37±10）ng／ml；sTyro3TK：（2．1±0．7）ng／ml]。血清sAxlTK水平与SLE患者外周血淋巴细胞数（r=0．266，P=0．002）、血红蛋白（r=0．480，P〈0．01）、血小板计数（r=0．374，P〈0．01）、白蛋白水平（r=-0．465，P〈0．01）、估算肾小球滤过率（r=-0．230，P=0．006）、C3（r=-0．399，P〈0．01）和C4（r=-0．374，P〈0．01）水平呈负相关，但与D-二聚体（r=0．371，P〈0．01）、肌酐（r=0．278，P〈0．01）、尿蛋白定量（24h）（r=0．383，P〈0．01）、ESR（r=0．422，P〈0．01）、ANA滴度（r=0．271，P=0．002）、抗dsDNA抗体（r=0．299，P〈0．01）、抗核小体抗体（r=0．263，P=-0．013）以及抗心磷脂抗体（r=0．309，P〈0．01）呈正相关。此外，血清sAxlTK浓度也与SLE患者SLEDAI评分呈正相关（r=0．307，P〈0．01），疾病活动组患者血清中sAxlTK浓度明显高于疾病稳定组[（64±17）ng／ml和（52±16）ng／ml；t=-3．939，P〈0．01]。结论SLE患者血清sAxlTK和sTyr03TK水平明显升高，且sAxlTK水平与自身抗体产生、血液系统和。肾脏系统损害等相关，可能提示狼疮病情活动。

Objective To explore the expression and clinical significance of soluble Axl and Tyro3 receptor tyrosine kinase in systemic lupus erythematosus （SLE）. Methods Sandwich enzyme linked immunosorbent assay （ELISA） was used to detect sAxlTK and sTyro3TK in the serum of 140 SLE patients, 150 disease controls and 100 healthy controls （HC）. The relationships between the serum levels of sAxlTK/sTyro3TK and clinical manifestations, laboratory parameters, disease activity were analyzed in SLE patients. Analysis of variance, Dunnett＇s t-test, chi-square test and spearman＇s test were used for statistical analysis. Results The concentrations of sAxlTK [（56±18） ng/ml] and sTyro3TK [（3.9±1.6） ng/ml] were both elevated in serum of SLE patients, which were significantly higher than disease controls [sAxlTK： （41±17） ng/ml; sTyro3TK： （2.6± 1.2） ng/ml] and healthy controls [sAxlTK： （37±10） ng/ml; sTyro3TK： （2.1±0.7） ng/ml]. The SLE sAxlTK levels were negatively correlated with lymphocyte count （r=-0.266, P=0.002）, hemoglobin （r=-0.480, P〈0.01）, platelet count （r=-0.374, P〈0.01）, albumin （r=-0.465, P〈0.01）, estimated glomerular filtration rate （eGFR, r=-0.230, P=0.006）, complement C3 （r=-0.399, P〈0.01） and complement C4 （r=-0.374, P〈0.01）. However, the levels of sAxlTK in SLE patients were positively correlated with D-dimer （r=0.371, P〈0.01）, ereatinine （r=0.278, P〈0.01）, 24-hour urinary protein quantification （r=0.383, P〈0.01）, erythroeyte sedimentation rate （r=0.422, P〈0.01）, titre of anti-nuelear antibodies （r=0.271, P=0.002）, anti-dsDNA antibody （r=0.299, P〈0.01）, antinueleosome antibody （r=0.263, P=0.013） and anti-eardiolipin antibody （r=0.309, P〈0.01）. In addition, the levels of serum sAxlTK in SLE patients showed positive correlation with the seores of SLEDAI （r=0.307, P〈0.01）. Comparisons of sAxlTK levels between patients with high and low disease activity demonstrated a higher level of sAxlTK in the former [（64±17） ng/ml vs （52±16） ng/ml; t=-3.939, P〈0.01]. Conclusion The levels of sAxlTK and sTyro3TK are elevated in the serum of SLE patients. The eoneentration of sAxlTK is eorrelated with autoantibodies produetion, hematological and renal involvement in SLE, whieh may be a serolgical marker for disease activity.