原发性舍格伦综合征患者血清ADAM17表达水平及其与病情程度的相关性研究

Study on the Expression Level of Serum ADAM17 in Patients with PrimarySjogren’s Syndrome and Its Correlation with the Severity of the Disease

目的 探究原发性舍格伦综合征(primary Sjogren syndrome,PSS)患者中血清解聚素金属蛋白酶17(a disintegrin and metalloprotease 17,ADAM17)表达水平及其与病情程度的关系。方法 选取东莞市人民医院风湿科在2022年2月1日~10月1日收治的86例PSS患者(PSS组),分活动期组和稳定期组,选取同期健康体检者43例作为对照组。采用酶联免疫吸附法(enzyme-linked immumosorbent assay, ELISA)检测血清ADAM17水平;采用免疫双扩散法检测血清抗SSA抗体和抗SSB抗体;采用流式细胞法检测血清炎症因子;采用Logistic回归分析PSS的影响因素;采用Pearson法分析血清ADAM17与PSS患者生化指标的相关性;采用spearman分析血清ADAM17与舍格伦综合征疾病活动指数(Sjogren's syndrome disease activity index,SSDAI)评分的相关性;采用多元线性回归分析影响SSDAI评分的因素。结果 稳定期组和活动期组抗SSA抗体阳性率、抗SSB抗体阳性率、肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)、白细胞介素-6(interleukin-6,IL-6)、白细胞介素-17(interleukin-17,IL-17)和ADAM17表达水平均高于对照组,白细胞介素-10(interleukin-10;IL-10)表达水平低于对照组,差异均有统计学意义(χ^(2)=4.288~53.030,t=4.860~33.081,均P <0.05);PSS患者活动期组抗SSA抗体阳性率、抗SSB抗体阳性率、TNF-α,IL-6,IL-17,ADAM17和SSDAI评分高于稳定期组,IL-10表达水平低于稳定期组,差异均有统计学意义(χ^(2)=11.764,13.936,t=8.186,4.862,13.295,5.108,9.846,均P <0.05);Logistic多因素回归分析表明,高水平ADAM17,抗SSA抗体阳性、抗SSB抗体阳性、高水平TNF-α,高水平IL-6,低水平IL-10和高水平IL-17是影响PSS发生的危险因素(P<0.05);根据Pearson相关性分析得知,PSS患者血清ADAM17水平与TNF-α,IL-6,IL-17水平呈正相关(r=0.543,0.582,0.578,均P <0.05),与IL-10水平呈负相关(r=-0.572,P <0.05);根据spearman相关性分析得知,血清ADAM17水平与SSDAI评分呈正相关(r=0.603,P <0.05)。多元线性回归分析结果表明,高水平ADAM17,抗SSA抗体阳性、抗SSB抗体阳性、高水平TNF-α,高水平IL-6,低水平IL-10和高水平IL-17是影响SSDAI评分的危险因素(P <0.05)。结论 PSS患者血清ADAM17水平显著升高,其与患者的病情严重程度相关,其表达水平随着病情严重程度增加而增加。

Objective To investigate the expression level of serum a disintegrin and metalloprotease domain-17(ADAM17)in patients with Primary Sjogren syndrome(PSS)and its relationship with the degree of disease.Methods A total of 86 PSS patients(PSS group)admitted by the Department of Rhumatology of Dongguan People’s Hospital from February 1,2022 to October 1,2022 were divided into active and stable groups,and 43 healthy physicalexaminers during the same period were selected as the control group.Serum adam17 level was detected by enzyme-linked immunosorbent assay.Serum anti-SSA antibody and anti-SSB antibody were detected by immunodcuble diffusion method.Flow cytometry was used to detect serum inflammatory factors.Logistic regression was used to analyze the influencing factors of PSS.Pearson method was used to analyze the correlatiion between serum ADAM17 and biochemical indexes of PSS patients.Spearman was used to analyze the correlation between serum ADAM17 and Sjogren’s syndrome disease activity index(SSDAI)score.And multivariate antibody positivity rates,tumor necrosis factor-α(TNF-α),interleukin-6(IL-6),interleukin-17(IL-17),ADAM1 and in stable group and active groups expression level were higher than that of control group,but interleukin-10 expression level was lower than that of control group,and the differences were statistically significant(χ^(2)=4.288~53.030;t=4.860~33.081,all P<0.05).Positive rates of anti-SSA antibody,anti-SSB antibodies,and TNF-αin the active phase group of PSS patients-α,IL-6,IL-17,ADAM17 and SSDAI scores were higher in the stable phase group,while IL-10 epression levels were lower in the stable phase group,and the differences were statistically significant(χ^(2)=11.764,13.936;t=8.186,4.862,13.295,5.108,9.846,all P<0.05).Logistic regression analysis showed that high level of ADAM17,positive anti-SSA antibody,positive anti-SSB antibody,high level of TNF-α,high level of IL-6,low level of IL-10,and high level of IL-17 were risk factors for PSS(all P<0.05).According to Pearson correlation analysis,the level of serum ADAM17 in PSS patients was positively correlated with TNF-α,IL-6,IL-17 levels(r=0.543,0.582,0.578,all P<0.05),and negatively correlated with IL-10 level(r=-0.572,P<0.05).According to spearman correlation analysis,serum ADAM17 levels were positively correlated with SSDAI scores(r=0.603,P<0.05).The results of multiple linear regression analysis showed that high level of ADAM17,positive anti-SSA antibody,positive anti-SSB antibody,high level of TNF-α,high level of IL-6,low level of IL-10,and high level of IL-10 were the risk factors affecting the SSDAI score(all P<0.05).Conclusion Serum ADAM17 levels in patients with PSS are significantly elevated,which correlated with the severity of the patient’s condition,and its expression level increases with increasing severity.