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目的:通过检测异基因造血干细胞移植(allo-HSCT)患者泪液中IL-36(α、β、γ)的表达情况,研究其与眼表微环境的相关性,并进一步分析其表达与眼部移植物抗宿主病(oGVHD)的关系。方法:前瞻性研究。选取2020-01就诊于我院血液科,行allo-HSCT患者35例70眼,另选取年龄、性别相匹配的健康志愿者35例70眼做为正常对照组。allo-HSCT组受检者术后随访3次,每3mo 1次,对术后是否出现眼部症状的受检者分为oGVHD组和非oGVHD(Non-oGVHD)组。对受试者进行眼表疾病指数(OSDI)问卷调查、泪液分泌试验(Schirmer试验)、泪膜破裂时间(TBUT)、角膜荧光素钠染色(FL)、结膜印迹细胞学染色(CIC)评估眼表状况,并用ELISA检测受检者泪液中IL-36(α、β、γ)表达水平。结果:正常对照组中,IL-36(α、β、γ)表达水平分别为74.32±5.27、70.02±8.43、97.41±8.66pg/mL; allo-HSCT组中,IL-36(α、β、γ)基线表达水平分别为77.27±7.03、74.53±7.53、100.77±9.74pg/mL,两组比较无差异(t=1.648、1.954、1.262,均P>0.05)。Non-oGVHD组不同时点IL-36α、IL-36β、IL-36γ比较均无差异(P>0.05),oGVHD组不同时点IL-36α、IL-36β、IL-36γ比较均有差异(P<0.05)。与Non-oGVHD组相比,oGVHD组不同时点的IL-36α、IL-36β均明显升高(均P<0.05)。oGVHD组泪液中IL-36(α、β、γ)表达水平与OSDI评分、FL、CIC呈正相关,与TBUT、Schirmer试验呈负相关(均P<0.05)。结论:检测泪液中IL-36(α、β、γ)水平对allo-HSCT后oGVHD的诊断有重要意义; 在oGVHD患者眼部不适症状出现之前,IL-36(α、β、γ)已在oGVHD患者泪液中高表达,且与眼表参数存在相关性。
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[Abstract]
AIM: To detect the expression of interleukin(IL)-36(α, β, γ)in tears of patients undergoing allogeneic hematopoietic stem cell transplantation(allo-HSCT), investigate its correlation with ocular surface microenvironment, and further analyze the relationship between its expression and ocular graft-versus-host disease(oGVHD).METHODS: Prospective study. A total of 35 patients(70 eyes)underwent allo-HSCT in the hematology department of our hospital in January 2020 were selected, and 35 healthy volunteers(70 eyes)with appropriate age and gender were selected as normal control group. The patients in the allo-HSCT group were followed up 3 times after operation once every 3mo. The subjects with postoperative ocular symptoms were divided into oGVHD and Non-oGVHD group.Ocular surface disease index(OSDI)questionnaire, Schirmer test, tear break-up time(TBUT), corneal fluorescein staining(FL), and conjunctival impression cytology(CIC)was conducted in three groups. Furthermore, the expression levels of IL-36(α,β,γ)in tears were detected by ELISA.RESULTS: In the normal control group, IL-36(α, β, γ)expression levels were 74.32±5.27, 70.02±8.43, 97.41±8.66 pg/mL, respectively; in the allo-HSCT group, IL-36(α, β, γ)baseline expression levels were 77.27±7.03, 74.53±7.53, 100.77±9.74 pg/mL, with no statistically significant differences between the two groups(t=1.648, 1.954, 1.262, all P>0.05). There were no significant differences in IL-36α, IL-36β and IL-36γ in Non-oGVHD group at different time points(P>0.05), while there were significant differences in IL-36α, IL-36β and IL-36γ in oGVHD group at different time points(P<0.05). Compared with Non-oGVHD group, the levels of IL-36α and IL-36β at different time points were significantly increased in oGVHD group(all P<0.05).IL-36(α, β, γ)of oGVHD group was positively correlated with OSDI score, FL and CIC, while it was negatively correlated with TBUT and Schirmer test(all P<0.05).CONCLUSION: Evaluation of levels of tear IL-36(α, β, γ)can be of significance in diagnosing oGVHD after allo-HSCT. IL-36(α, β, γ)is highly expressed in the tears of oGVHD patients before the onset of ocular symptoms, and it is correlated with the ocular surface parameters.
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