狼疮性肾炎患者IL-15表达情况及免疫病理损伤特点
|
摘要
目的探讨IL-15在狼疮性肾炎(lupus nephritis,LN)患者中的表达及其免疫病理损伤特征。方法采用资料收集及回顾性方法,研究时间为2016年2月到2017年6月,选择在我院住院诊治的系统性红斑狼疮(systemic lupus erythematosus,SLE)患者112例作为研究对象,根据是否合并LN情况分为LN组(62例)与SLE组(60例),记录2组患者的免疫病理损伤特点,检测IL-15等血液学指标,随访预后情况并进行相关性分析。结果 LN组的肾小管萎缩、间质纤维化发生率显著高于SLE组(P<0.05),2组肾小球硬化与纤维性新月体发生率对比差异无统计学意义(P>0.05)。LN组的CysC、TNF-α、IL-1β、IL-6都显著高于SLE组(P<0.05)。LN组的IL-15值为(16.30±11.49)ng/L,显著高于SLE组的(8.20±2.94)ng/L(t=8.588,P=0.003)。SLE组的恶性心律失常、脑卒中、心源性死亡、心衰、冠脉事件等MACE发生率为5.0%,LN组为24.2%,LN组显著高于SLE组(P<0.05)。在LN组中,Spearman检验显示患者的IL-15值与肾小管萎缩、间质纤维化、CysC、IL-1β、IL-6、TNF-α、MACE等都呈显著正相关(P<0.05)。结论 IL-15在LN患者中呈现高表达情况,伴随有严重的免疫病理损伤,两者存在显著相关性,可影响患者的病情与预后。
To investigate the expression of IL-15 in patients with lupus nephritis(LN) and its relationship with immunopathological damage, total of 62 LN patients(LN group) and 60 systemic lupus erythematosus(SLE) patients(SLE group) were recruited from our hospital during February 2016 to June 2017, and evaluated with retrospective analysis. The immunopathological features of the two groups were recorded; the hematological indexes such as IL-15 were detected, the prognosis were followed up, and correlation analysis was carried out. Data showed that the incidence of tubular atrophy and interstitial fibrosis in the LN group were significantly higher than that in the SLE group(P<0.05), while there were no significant difference in the incidence of glomerular sclerosis and fibrotic crescent between the two groups(P>0.05). Furthermore, the levels of CysC, TNF-α, IL-1β and IL-6 in the LN group were significantly higher than those in the SLE group(P<0.05). The IL-15 level of the LN group was(16.30±11.49) ng/L, which was significantly higher than that of the SLE group of(8.20±2.94) ng/L(t=8.588, P=0.003). LN group demonstrated a higher incidence rate(24.2%) of major adverse cardiovascular events(MACE, including malignant arrhythmia, stroke, cardiac death, recurrent heart failure, recurrent coronary events), as compared with SLE group(5.0%)(P<0.05). Spearman's test showed that IL-15 level was positively correlated with renal tubularatrophy, interstitial fibrosis, CysC, IL-1β, IL-6, TNF-α, and MACE(P<0.05) in the LN group. Taken together, IL-15 is highly expressed in LN patients,accompaning with severe immunopathological damage,which are significantly correlated with each other, and may affect the patient's condition and prognosis.
To investigate the expression of IL-15 in patients with lupus nephritis(LN) and its relationship with immunopathological damage, total of 62 LN patients(LN group) and 60 systemic lupus erythematosus(SLE) patients(SLE group) were recruited from our hospital during February 2016 to June 2017, and evaluated with retrospective analysis. The immunopathological features of the two groups were recorded; the hematological indexes such as IL-15 were detected, the prognosis were followed up, and correlation analysis was carried out. Data showed that the incidence of tubular atrophy and interstitial fibrosis in the LN group were significantly higher than that in the SLE group(P<0.05), while there were no significant difference in the incidence of glomerular sclerosis and fibrotic crescent between the two groups(P>0.05). Furthermore, the levels of CysC, TNF-α, IL-1β and IL-6 in the LN group were significantly higher than those in the SLE group(P<0.05). The IL-15 level of the LN group was(16.30±11.49) ng/L, which was significantly higher than that of the SLE group of(8.20±2.94) ng/L(t=8.588, P=0.003). LN group demonstrated a higher incidence rate(24.2%) of major adverse cardiovascular events(MACE, including malignant arrhythmia, stroke, cardiac death, recurrent heart failure, recurrent coronary events), as compared with SLE group(5.0%)(P<0.05). Spearman's test showed that IL-15 level was positively correlated with renal tubularatrophy, interstitial fibrosis, CysC, IL-1β, IL-6, TNF-α, and MACE(P<0.05) in the LN group. Taken together, IL-15 is highly expressed in LN patients,accompaning with severe immunopathological damage,which are significantly correlated with each other, and may affect the patient's condition and prognosis.
引文
[1]Nu?ez Ortiz N,Moore LJ,Jarungsriapisit J,et al.Atlantic salmon post-smolts adapted for a longer time to seawater develop an effective humoral and cellular immune response against Salmonid alphavirus[J].Fish Shellfish Immunol,2018,31(82):579-590.
[2]黄晓华,陈运转.吗替麦考酚酯胶囊对狼疮性肾炎患者外周血IL-18、IL-15水平的影响分析[J].中国现代医药杂志,2017,19(12):68-69.
[3]Liu HX,Zhou XQ,Jiang WD,et al.Optimalα-lipoic acid strengthen immunity of young grass carp(Ctenopharyngodon idella)by enhancing immune function of head kidney,spleen and skin[J].Fish Shellfish Immunol,2018,9(80):600-617.
[4]顾丽萍,杨贵丽,陈幼发,等.Th22细胞及其功能分子IL-22在狼疮性肾炎中的作用研究[J].中国免疫学杂志,2017,33(5):755-758.
[5]Feng F,Liu Y,Liu G,et al.Human CD8(+)CD28(-)Tsuppressor cells expanded by IL-15 in vitro suppress in an allospecific and programmed cell death protein 1-dependent manner[J].Front Immunol,2018,22(9):1442.
[6]Idborg H,Eketj?ll S,Pettersson S,et al.TNF-αand plasma albumin as biomarkers of disease activity in systemic lupus erythematosus[J].Lupus Sci Med,2018,5(1):e000260.
[7]Ekart R,Bevc S,Hojs N,et al.Relationship between subendocardial viability ratio and hemoglobin in patients with chronic kidney disease[J].Clin Nephrol,2017,88(13):22-26.
[8]聂英坤,张凤山,朱绿松,等.FcγRⅡb与狼疮性肾炎病理活动的相关性[J].免疫学杂志,2007,23(3):351.
[9]Berti A,Warner R,Johnson K,et al.Brief report:circulating cytokine profiles and antineutrophil cytoplasmic antibody specificity in patients with antineutrophil cytoplasmic antibody-associated vasculitis[J].Arthritis Rheumatol,2018,70(7):1114-1121.
[10]Wang XZ,Jiang WD,Feng L,et al.Low or excess levels of dietary cholesterol impaired immunity and aggravated inflammation response in young grass carp(Ctenopharyngodon idella)[J].Fish Shellfish Immunol,2018,7(78):202-221.
[11]Kiang JG,Smith JT,Anderson MN,et al.Hemorrhage enhances cytokine,complement component 3,and caspase-3,and regulates microRNAs associated with intestinal damage after whole-body gamma-irradiation in combined injury[J].PLoS One,2017,12(9):e0184393.
[12]Villarino AV,SciumèG,Davis FP,et al.Subset-and tissue-defined STAT5 thresholds control homeostasis and function of innate lymphoid cells[J].J Exp Med,2017,214(10):2999-3014.
[13]Dedeoglu B,Litjens NHR,Klepper M,et al.CD4(+)CD28(null)T cells are not alloreactive unless stimulated by interleukin-15[J].Am J Transplant,2018,18(2):341-350.
[14]甘露.Th22细胞与自身免疫疾病及相关肾损伤的关系[J].国际泌尿系统杂志,2017,37(4):620-623.
[15]Watson EL,Viana JL,Wimbury D,et al.The effect of resistance exercise on inflammatory and myogenic markers in patients with chronic kidney disease[J].Front Physiol,2017,28(8):541.
[16]Moore CA,Iasella CJ,Venkataramanan R,et al.Janus kinase inhibition for immunosuppression in solid organ transplantation:Is there a role in complex immunologic challenges?[J].Hum Immunol,2017,78(2):64-71.
[17]Pellom ST Jr,Dudimah DF,Thounaojam MC,et al.Bortezomib augments lymphocyte stimulatory cytokine signaling in the tumor microenvironment to sustain CD8+Tcell antitumor function[J].Oncotarget,2017,8(5):8604-8621.
[18]彭薇,申利平.狼疮肾炎患者外周血中ICOS、OX40、CD40表达量与病情活动的相关性研究[J].海南医学院学报,2017,23(15):2067-2070.
[19]Assadiasl S,Sepanjnia A,Aghili B,et al.Natural killer cell subsets and IL-2,IL-15,and IL-18 genes expressions in chronic kidney allograft dysfunction and graft function in kidney allograft recipients[J].Int J Organ Transplant Med,2016,7(4):212-217.
[20]沈辉,盛晗,朱玉强,等.CD80双价抗体对降植烷诱导的小鼠狼疮样肾炎模型的免疫干预效应研究[J].中华微生物学和免疫学杂志,2017,37(9):688-694.
[21]Luque Y,Cathelin D,Vandermeersch S,et al.Glomerular common gamma chain confers B-and T-cell-independent protection against glomerulonephritis[J].Kidney Int,2017,91(5):1146-1158.
[22]袁一孟,郑戈.连续血液净化辅助甲基强的松龙及环磷酰胺联合冲击对狼疮性肾炎合并狼疮性肺炎患者Th1/Th2细胞因子失衡的影响[J].临床肺科杂志,2017,22(8):1427-1430.
[23]张书锋,刘翠华,吴丽娟,等.狼疮性肾炎患儿医院感染血清与尿液白细胞介素水平变化研究[J].中华医院感染学杂志,2016,26(4):922-924.
[24]Idborg H,Eketj?ll S,Pettersson S,et al.TNF-αand plasma albumin as biomarkers of disease activity in systemic lupus erythematosus[J].Lupus Sci Med,2018,5(1):e000260.
[25]Landolt Marticorena C,Prokopec SD,Morrison S,et al.Adiscrete cluster of urinary biomarkers discriminates between active systemic lupus erythematosus patients with and without glomerulonephritis[J].Arthritis Res Ther,2016,18(1):218.
[26]唐飞飞,蒋宇婷,褚夫宝,等.IL-17与狼疮性肾炎关系的研究新进展[J].现代生物医学进展,2016,16(9):1782-1784,1777.
[2]黄晓华,陈运转.吗替麦考酚酯胶囊对狼疮性肾炎患者外周血IL-18、IL-15水平的影响分析[J].中国现代医药杂志,2017,19(12):68-69.
[3]Liu HX,Zhou XQ,Jiang WD,et al.Optimalα-lipoic acid strengthen immunity of young grass carp(Ctenopharyngodon idella)by enhancing immune function of head kidney,spleen and skin[J].Fish Shellfish Immunol,2018,9(80):600-617.
[4]顾丽萍,杨贵丽,陈幼发,等.Th22细胞及其功能分子IL-22在狼疮性肾炎中的作用研究[J].中国免疫学杂志,2017,33(5):755-758.
[5]Feng F,Liu Y,Liu G,et al.Human CD8(+)CD28(-)Tsuppressor cells expanded by IL-15 in vitro suppress in an allospecific and programmed cell death protein 1-dependent manner[J].Front Immunol,2018,22(9):1442.
[6]Idborg H,Eketj?ll S,Pettersson S,et al.TNF-αand plasma albumin as biomarkers of disease activity in systemic lupus erythematosus[J].Lupus Sci Med,2018,5(1):e000260.
[7]Ekart R,Bevc S,Hojs N,et al.Relationship between subendocardial viability ratio and hemoglobin in patients with chronic kidney disease[J].Clin Nephrol,2017,88(13):22-26.
[8]聂英坤,张凤山,朱绿松,等.FcγRⅡb与狼疮性肾炎病理活动的相关性[J].免疫学杂志,2007,23(3):351.
[9]Berti A,Warner R,Johnson K,et al.Brief report:circulating cytokine profiles and antineutrophil cytoplasmic antibody specificity in patients with antineutrophil cytoplasmic antibody-associated vasculitis[J].Arthritis Rheumatol,2018,70(7):1114-1121.
[10]Wang XZ,Jiang WD,Feng L,et al.Low or excess levels of dietary cholesterol impaired immunity and aggravated inflammation response in young grass carp(Ctenopharyngodon idella)[J].Fish Shellfish Immunol,2018,7(78):202-221.
[11]Kiang JG,Smith JT,Anderson MN,et al.Hemorrhage enhances cytokine,complement component 3,and caspase-3,and regulates microRNAs associated with intestinal damage after whole-body gamma-irradiation in combined injury[J].PLoS One,2017,12(9):e0184393.
[12]Villarino AV,SciumèG,Davis FP,et al.Subset-and tissue-defined STAT5 thresholds control homeostasis and function of innate lymphoid cells[J].J Exp Med,2017,214(10):2999-3014.
[13]Dedeoglu B,Litjens NHR,Klepper M,et al.CD4(+)CD28(null)T cells are not alloreactive unless stimulated by interleukin-15[J].Am J Transplant,2018,18(2):341-350.
[14]甘露.Th22细胞与自身免疫疾病及相关肾损伤的关系[J].国际泌尿系统杂志,2017,37(4):620-623.
[15]Watson EL,Viana JL,Wimbury D,et al.The effect of resistance exercise on inflammatory and myogenic markers in patients with chronic kidney disease[J].Front Physiol,2017,28(8):541.
[16]Moore CA,Iasella CJ,Venkataramanan R,et al.Janus kinase inhibition for immunosuppression in solid organ transplantation:Is there a role in complex immunologic challenges?[J].Hum Immunol,2017,78(2):64-71.
[17]Pellom ST Jr,Dudimah DF,Thounaojam MC,et al.Bortezomib augments lymphocyte stimulatory cytokine signaling in the tumor microenvironment to sustain CD8+Tcell antitumor function[J].Oncotarget,2017,8(5):8604-8621.
[18]彭薇,申利平.狼疮肾炎患者外周血中ICOS、OX40、CD40表达量与病情活动的相关性研究[J].海南医学院学报,2017,23(15):2067-2070.
[19]Assadiasl S,Sepanjnia A,Aghili B,et al.Natural killer cell subsets and IL-2,IL-15,and IL-18 genes expressions in chronic kidney allograft dysfunction and graft function in kidney allograft recipients[J].Int J Organ Transplant Med,2016,7(4):212-217.
[20]沈辉,盛晗,朱玉强,等.CD80双价抗体对降植烷诱导的小鼠狼疮样肾炎模型的免疫干预效应研究[J].中华微生物学和免疫学杂志,2017,37(9):688-694.
[21]Luque Y,Cathelin D,Vandermeersch S,et al.Glomerular common gamma chain confers B-and T-cell-independent protection against glomerulonephritis[J].Kidney Int,2017,91(5):1146-1158.
[22]袁一孟,郑戈.连续血液净化辅助甲基强的松龙及环磷酰胺联合冲击对狼疮性肾炎合并狼疮性肺炎患者Th1/Th2细胞因子失衡的影响[J].临床肺科杂志,2017,22(8):1427-1430.
[23]张书锋,刘翠华,吴丽娟,等.狼疮性肾炎患儿医院感染血清与尿液白细胞介素水平变化研究[J].中华医院感染学杂志,2016,26(4):922-924.
[24]Idborg H,Eketj?ll S,Pettersson S,et al.TNF-αand plasma albumin as biomarkers of disease activity in systemic lupus erythematosus[J].Lupus Sci Med,2018,5(1):e000260.
[25]Landolt Marticorena C,Prokopec SD,Morrison S,et al.Adiscrete cluster of urinary biomarkers discriminates between active systemic lupus erythematosus patients with and without glomerulonephritis[J].Arthritis Res Ther,2016,18(1):218.
[26]唐飞飞,蒋宇婷,褚夫宝,等.IL-17与狼疮性肾炎关系的研究新进展[J].现代生物医学进展,2016,16(9):1782-1784,1777.