血清白细胞介素36亚家族作为狼疮肾炎疾病进展生物标志物的探索性研究

刘超; 余晓洋; 王志刚; 赵灿

doi:10.3969/j.issn.1671-2390.2023.10.002

血清白细胞介素36亚家族作为狼疮肾炎疾病进展生物标志物的探索性研究

Exploratory study of serum IL-36 subfamily as biomarkers of disease progression in lupus nephritis

摘要

摘要:
目的探讨血清白细胞介素（interleukin，IL）36亚家族是否可以作为狼疮肾炎（lupus nephritis，LN）疾病进展的生物标志物。
方法选取2017年3月至2020年4月期间西安交通大学第一附属医院肾脏内科收治的103例系统性红斑狼疮（systemic lupus erythematosus，SLE）患者作为研究对象，其中30例患有LN被纳入LN组，而肾功能正常的73例SLE患者纳入非LN组，另招募83名同期体检健康且无任何肾脏疾病史的志愿者作为健康对照组。采用酶联免疫吸附试验法测定血清IL-36α、IL-36β、IL-36γ、IL-36Ra、IL-17水平。
结果与健康对照组相比，非LN组和LN组患者血清IL-36α13.12（9.01，17.95）ng/L、21.24（11.41，26.37）ng/L比10.06（6.80，12.34）ng/L和IL-1744.18（32.78，66.95）ng/L、49.73（33.26，91.08）ng/L比33.14（20.67，43.07）ng/L水平均升高，且LN组较非LN组升高更显著（P＜0.05）。LN组患者血清IL-36β25.67（11.52，48.52）ng/L比8.60（4.59，13.68）ng/L、11.44（6.45，26.91）ng/L水平亦高于健康对照组和非LN组，同时血清IL-36Ra32.88（17.47，51.69）ng/L比98.17（45.93，161.80）ng/L、49.11（26.40，92.52）ng/L水平低于健康对照组和非LN组（P＜0.05）。在正向逐步法中，观察到较高水平的IL-36α增加了SLE患者蛋白尿的风险（OR=1.346，95%CI：1.134～1.596，P=0.001）。此外，LN患者血清IL-36α与SLE疾病活动度评分（disease activity index，DAI）、肾脏SLEDAI、系统性狼疮国际临床协作组和美国风湿病学学会损伤指数评分、血清IL-17均呈显著正相关（P＜0.05），与IL-36Ra、补体C3水平呈负相关（P＜0.05）。糖皮质激素联合或不联合免疫抑制剂治疗可降低SLE患者血清IL-36α水平（P＜0.05）。
结论 IL-36α可能是与SLE蛋白尿相关的生物标志物，且独立于其他混杂因素，其作用机制可能是参与辅助性T细胞（T helper cells，Th）17细胞因子的调节。

Abstract:
Objective To explore whether or not serum interleukin (IL)-36 subfamily may serve as biomarkers for disease progression in lupus nephritis (LN).
Methods From March 2017 to April 2020, 103 patients hospitalized with systemic lupus erythematosus (SLE) at Department of Nephrology, First Affiliated Hospital of Xi'an Jiaotong University were selected as research subjects. They were assigned into two groups of LN (n=30) and non-LN (n=73). In addition, 83 healthy volunteers without a history of kidney disease were recruited as healthy control group. Serum levels of IL-36α、IL-36β、IL-36γ、IL-36Ra and IL-17 were measured by enzyme-linked immunosorbent assay (ELISA).
Results Compared with healthy control group, serum levels of IL-36α 13.12(9.01, 17.95)ng/L, 21.24(11.41, 26.37)ng/L vs 10.06 (6.80, 12.34)ng/L and IL-17 44.18(32.78, 66.95)ng/L, 49.73(33.26, 91.08)ng/L vs 33.14(20.67, 43.07)ng/L rose in non-LN and LN groups and the increase was more significant in LN group than that in non-LN group (P<0.05). Serum level of IL-36β was also higher in LN group than that in healthy control and non-LN groups 25.67(11.52, 48.52)ng/L vs 8.60(4.59, 13.68)ng/L, 11.44(6.45, 26.91)ng/L while the serum level of IL-36Ra 32.88(17.47, 51.69)ng/L vs 98.17(45.93, 161.80)ng/L, 49.11(26.40, 92.52)ng/L was lower than that in healthy control and non-LN groups (P<0.05). In positive stepwise method, higher levels of IL-36α might elevate the risk of proteinuria in SLE patients (OR=1.346, 95%CI:1.134-1.596, P=0.001). And serum IL-36α in LN patients was significantly correlated positively with SLE disease activity index (SLEDAI), renal SLEDAI (rSLEDAI), SLICC/ACR injury index (SDI) and serum IL-17 (P<0.05) and negatively with levels of IL-36Ra and complement C3 (P<0.05). Glucocorticoid with or without immunosuppressant could lower serum level of IL-36 in SLE patients (P<0.05).
Conclusions Independent of other confounding factors, IL-36α may be a biomarker associated with SLE proteinuria. And its mechanism of action may be associated with the regulation of Th17 cytokines.

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