Abstract
目的
研究抗α烯醇化酶抗体[抗ENO1(enolase 1)抗体]水平与狼疮性视网膜病变及系统性红斑狼疮(systemic lupus erythematosus，SLE)活动性的相关性。
方法
选择2017年4月至2022年5月北京大学人民医院风湿免疫科住院的活动性SLE患者，分为SLE合并和不合并狼疮性视网膜病变两组，同时以年龄匹配且不合并视网膜病变的健康志愿者作为阴性对照组，应用酶联免疫吸附试验(enzyme-linked immunosorbent assay, ELISA)检测各组血清中抗ENO1抗体水平和阳性率，同时收集前两组SLE患者活动性相关的临床特征和实验室结果，分析抗ENO1抗体水平与其他SLE临床资料与实验室指标之间的相关性。
结果
SLE合并狼疮性视网膜病变患者眼底出现了多种视网膜病变，占比排名前三的是视网膜出血(14/32，43.75%)、棉絮斑(8/32，25.00%)和视网膜静脉阻塞(3/32，9.38%)。在32例SLE合并狼疮性视网膜病变患者中，有13例(40.63%)出现了两种及以上的视网膜病变。SLE合并狼疮性视网膜病变患者的血清抗ENO1抗体水平和阳性率显著高于不合并狼疮性视网膜病变组(P < 0.05)，狼疮性视网膜病变患者具有更高的SLE疾病活动度评分(P < 0.001)。将SLE患者分为抗ENO1抗体阳性和阴性两组进行研究发现，在临床表现上，抗ENO1抗体阳性与发热和尿潜血有关的可能性大(P=0.011，P=0.042)；在实验室指标上，与抗ENO1抗体阴性的SLE患者相比，抗ENO1抗体阳性的SLE患者具有更高的红细胞沉降率(erythrocyte sedimentation rate, ESR)、免疫球蛋白G(immunoglobulin G, IgG)和血小板计数(blood platelet count, PLT，P < 0.01)，此外，抗ENO1抗体阳性患者还具有更高的免疫球蛋白A(immunoglobulin A, IgA，P < 0.05)。
结论
合并狼疮性视网膜病变的SLE患者血清中抗ENO1抗体的水平和阳性率明显升高，且具有更高的疾病活动性。
Keywords: 系统性红斑狼疮, 狼疮性视网膜病变, 自身抗体, α烯醇化酶, 抗ENO1抗体
Abstract
Objective
To build bridges between anti-α enolase antibody (anti-enolase 1 antibody, anti-ENO1 antibody) and common clinical and laboratory characteristics of systemic lupus erythematosus (SLE) and to analyze the role of anti-ENO1 antibody in the evaluation of SLE disease activity.
Methods
The SLE patients with retinopathy and without retinopathy were enrolled in the study, as well as healthy individuals whose gender and age matched with those of the SLE patients. Serum anti-ENO1 antibodies were measured using enzyme-linked immunosorbent assay (ELISA), presenting as intra-group positive rate and arbitrary units (AU) value. Clinical and laboratory data were obtained from medical records.
Results
The SLE retinopathy patients represented various fundus abnormalities. Ranked by percentage, the top three retinopathies were retinal hemorrhage (14/32, 43.75%), cotton-wool spots (8/32, 25.00%) and retinal vein occlusion (3/32, 9.38%). Among the 32 SLE retinopathy patients, 13 (40.63%) suffered from two or more fundus abnormalities. The positive rate and AU value of the SLE patients were higher than of the SLE patients without retinopathy (68.75% vs. 46.00%, P=0.043; 16.11%±10.35% vs. 12.06%±6.47%, P=0.045). Besides, the positive rate and AU value of the two SLE groups were both significantly higher than those of the healthy control group (P < 0.001). Compared with the SLE-without-retinopathy group, the systemic lupus erythematosus disease activity index (SLEDAI)-2000 of the SLE retinopathy patients were significantly higher than those of the SLE patients without retinopathy (17.41±4.25 vs. 9.48±5.35, P < 0.001). Dividing all the SLE patients into an anti-ENO1-positive group and an anti-ENO1-negative group, we found that anti-ENO1-positive was more likely to be correlated to developing fever and positive result of urine occult blood (P=0.011, P=0.042). Comparing with the patients with negative anti-ENO1 antibodies, the patients with positive anti-ENO1 antibodies had significantly higher erythrocyte sedimentation rate (ESR) [the median (range) was 29.50 (1.52-110.00) mg/L vs. 12.00 (4.00-101.00) mg/L, P=0.001], higher immunoglobulin G (IgG) [the median (range) was 14.30 (4.02-37.80) g/L vs. 10.46 (2.50-25.73) g/L, P=0.000 3], and higher blood platelet count (PLT) [(205.87×109±67.98×109) /L vs. (164.57×109±69.57×109) /L, P=0.008], as well as higher immunoglobulin A (IgA) [the median (range) was 2.85 (0.07-27.00) g/L vs. 2.05 (0.42-4.36) g/L, P=0.014].
Conclusion
The positive rate and AU value of anti-ENO1 antibody suggested higher SLE disease activity and they were elevated in SLE and SLE retinopathy.
Keywords: Systemic lupus erythematosus, Retinopathy, Autoantibody, α-enolase, Anti-ENO1 antibody
系统性红斑狼疮(systemic lupus erythematosus, SLE)是一种多系统受损的自身免疫性结缔组织病，自身免疫性小血管炎是其主要病理改变之一。大约三分之一的SLE患者会合并有眼部表现[1]，其中对视力威胁最严重的就是狼疮性视网膜病变。狼疮性视网膜病变可以表现为视网膜出现棉絮斑、视网膜动脉狭窄、静脉曲张、毛细血管扩张、微动脉瘤、视网膜水肿、视网膜出血和硬性渗出[1-5]，部分患者会出现更严重的视网膜病变(包括新生血管、视网膜脱离、缺血性视神经病变和视网膜血管阻塞)[5-9]。狼疮性视网膜病变严重影响视力，因此早期诊断和早期治疗非常重要，但是目前关于狼疮性视网膜病变的血清学标志物研究较少见。近期研究显示SLE患者的外周血血清中可检测到抗ENO1(enolase 1)抗体(抗ENO1抗体对应的抗原为α烯醇化酶)[10-11]，此抗体对应的抗原在视网膜内外层均有定位[12-13]，由此推测抗ENO1抗体可能与狼疮性视网膜病变之间存在一定的关联性。本研究旨在通过酶联免疫吸附试验(enzyme-linked immunosorbent assay, ELISA)检测血清中的抗ENO1抗体，研究其抗体水平和阳性率与狼疮性视网膜病变及SLE活动性之间的相关性。
1. 资料与方法
1.1. 病例选择
本研究为横断面观察性研究，选择2017年4月至2022年5月北京大学人民医院风湿免疫科住院的活动性SLE患者为研究对象，SLE的诊断标准依据2009年欧洲抗风湿病联盟(European League Against Rheumatism, EULAR)/美国风湿病学会(American College of Rheumatology, ACR)修订的SLE诊断标准，进一步依据是否具有狼疮性视网膜病变分为合并狼疮性视网膜病变组与不合并狼疮性视网膜病变组。狼疮性视网膜病变的诊断由眼科医生根据患者眼部表现和视网膜特征表现而确定。阴性对照组纳入同期在北京大学人民医院进行体检的年龄及性别匹配且不合并视网膜病变的健康志愿者。
本研究符合《世界医学大会赫尔辛基宣言》(the World Medical Association Declaration of Helsinki)，且研究开始前已经北京大学人民医院医学伦理委员会审查批准(2021PHB028-001)，所有参与研究者均签署知情同意书。
排除标准：(1)有临床表现或实验室检查结果提示现证感染或肿瘤者；(2)孕期或哺乳期者；(3)曾经或正在服用可能导致眼部病变药物[羟氯喹(hydroxychloroquine, HCQ)或激素]者；(4)有继发于其他原发病的眼底病变(糖尿病性视网膜病变、高血压性视网膜改变等)者；(5)由于眼部任何病变导致无法确定视网膜情况者；(6)无法配合风湿免疫科或眼科的专业检查项目者。
1.2. 血清抗ENO1抗体的检测
使用人α烯醇化酶抗体IgG酶联免疫试剂盒(CSB-EQ027775HU, CUSABIO BIOTECH CO., LTD.武汉华美生物工程有限公司)检测各组血清中抗ENO1抗体IgG。将所有试剂在25 ℃室温下平衡30 min，用样本稀释液将血清样本按体积比1 ∶2 000稀释，用酶结合物稀释液将酶结合物(辣根过氧化物酶标记的抗人IgG)按体积比1 ∶100稀释为酶结合物工作液。特异抗原包被的96孔酶标板上设置一个空白孔，不加任何液体，其余每个孔中加入阳性对照、阴性对照或稀释后的血清样本各100 μL，混匀后置于37 ℃温育30 min；弃去孔内液体后洗板3次(每孔加入200 μL洗液，浸泡2 min)，每孔加入酶结合物工作液100 μL(空白孔除外)，混匀后置于37 ℃温育30 min；弃去孔内液体后洗板5次，末次洗涤后弃去洗涤液；每孔加入底物(3, 3′, 5, 5′-四甲基联苯胺, TMB)溶液90 μL，震荡混匀后37 ℃避光显色20 min；每孔加入终止液50 μL，反应终止后10 min内用酶标仪在450 nm波长下测量各孔的光密度(D)值。
定性判断时所用的临界值为同批次实验阴性对照组平均值的2.1倍，待测样本的光密度高于此值则为阳性，低于此值则为阴性。定量分析时，根据标准血清(即阳性对照)将光密度换算为AU(arbitrary units)值：
AU值=[(待测血清D值-空白孔D值)/(标准血清D值-空白孔D值)] ×100%。
1.3. 临床资料和实验室指标的收集
收集受试者采集血清一周之内的临床资料及实验室指标，临床资料包括性别、年龄、病程、临床表现、SLE疾病活动度评分-2000(systemic lupus erythematosus disease activity index-2000, SLEDAI-2000)、用药史；实验室指标包括C反应蛋白(C-reactive protein, CRP)、红细胞沉降率(erythrocyte sedimentation rate, ESR)、免疫球蛋白A(immunoglobulin A, IgA)、免疫球蛋白G(immunoglobulin G, IgG)、免疫球蛋白M(immunoglobulin M, IgM)、补体3(complement 3, C3)、补体4(complement 4, C4)、白细胞计数(white blood cell count, WBC)、血红蛋白含量(hemoglobin, HB)、血小板计数(blood platelet count, PLT)、抗双链DNA抗体(anti-double-stranded DNA antibody, 抗dsDNA抗体)水平等。
所有受试者均接受眼科检查，包括双眼最佳矫正视力(best-corrected visual acuity, BCVA)、眼内压(intraocular pressure, IOP)、散瞳后眼底检查、彩色立体眼底相(欧堡200Tx激光扫描检眼镜，英国)、光学相干断层成像(optical coherence tomography, OCT)(光视RTVue-XR Avanti OCT，美国，或蔡司Cirrus 5000 HD-OCT，德国)和眼底荧光血管造影(fundus fluorescein angiography, FFA，蔡司FF450plus眼底照相机，德国)。
1.4. 统计学分析
使用R 4.0.3和R Studio 1.3.1093进行统计分析，计量资料是否服从正态分布采用Shapiro-Wilk检验。服从正态分布的连续性变量以均数±标准差表示，组间比较采用双独立样本t检验，采用单因素方差分析(one-way ANOVA)进行多组间比较，方差分析后采用Tukey HSD法进行事后检验；不服从正态分布的连续变量以中位数(范围)表示，组间比较采用Mann-Whitney U检验，采用Kruskal-Wallis检验进行多组间比较。二分类变量采用卡方检验，有序分类变量采用卡方检验，必要时使用连续校正的卡方检验。统计检验均为双侧检验，P < 0.05认为差异有统计学意义。
2. 结果
2.1. 受试者资料
SLE合并狼疮性视网膜病变组患者32例，SLE不合并狼疮性视网膜病变组患者50例，阴性对照组健康志愿者50例纳入本研究，三组的人口学特征间的差异无统计学意义(表 1)。
表 1.
受试者人口学资料比较
Demographic data of all the three groups
| Items | SLE retinopathy | SLE without retinopathy | Healthy control | P value |
| SLE, systemic lupus erythematosus. | ||||
| Age/years, x±s | 43.40±17.31 | 35.58±14.87 | 39.03±19.39 | 0.335 |
| Range of age/years | 18－73 | 17－70 | 19－74 | - |
| Sample size, n | 32 | 50 | 50 | - |
| Gender, n (%) | ||||
| Male | 7 (21.87) | 7 (14.00) | 6 (12.00) | 0.458 |
| Female | 25 (78.13) | 43 (86.00) | 44 (88.00) | |
| Disease duration | ||||
| Median/years | 10.5 | 6 | - | 0.156 |
| Range | 20 days to 50 years | 6 months to 42 years | - | - |
2.2. 两组SLE患者的临床表现
SLE合并狼疮性视网膜病变组出现的眼底异常包括棉絮斑(8/32，25.00%)、视网膜出血(14/32，43.75%)、黄斑水肿(2/32，6.25%)、视网膜动脉阻塞(2/32，6.25%)、视网膜静脉阻塞(3/32，9.38%)、视网膜血管炎(7/32，21.87%)、视乳头水肿(2/32，6.25%)、视网膜脱离(1/32，3.13%)、视神经萎缩(2/32，6.25%)和脉络膜脱离(1/32，3.13%)，其中13例(40.63%)有两种及以上的眼底异常。
两组在各项全身临床表现(发热、皮疹、蝶形红斑、关节痛、脱发、口腔溃疡、光过敏、雷诺现象、尿隐血、蛋白尿、胸膜炎及心包炎)和实验室检查指标(抗双链DNA抗体、抗核抗体、抗Sm抗体、抗U1核糖核蛋白抗体、抗SSA抗体、抗SSB抗体)的差异均无统计学意义(表 2)，但合并狼疮性视网膜病变组患者的SLE活动性评分SLEDAI-2000显著高于不合并狼疮性视网膜病变组患者(17.41±4.25 vs.9.48±5.35, P < 0.001)。
表 2.
两组SLE患者的临床特点和实验室指标
Clinical and laboratory characteristics of the two SLE groups
| Items | SLE retinopathy, n=32 | SLE without retinopathy, n=50 | P value |
| SLEDAI, systemic lupus erythematosus disease activity index; Tmax, the highest temperature of the patients who had a fever during the disease; anti-dsDNA, anti-double-stranded DNA antibody; ANA, antinuclear antibody; anti-Sm, anti-Smith antibody; anti-U1 RNP, anti-U1 ribonucleoprotein antibody; anti-SSA, anti-Sjögren syndrome A antibody; anti-SSB, anti-Sjögren syndrome B antibody. # P < 0.01. | |||
| SLEDAI-2000, x±s | 17.41±4.25 | 9.48±5.35 | < 0.001# |
| Clinical Features | |||
| Fever, n (%) | 22 (68.75) | 35 (70.00) | 0.905 |
| Tmax/℃, x±s | 38.92±0.76 | 38.93±0.76 | 0.980 |
| Rash, n (%) | 13 (40.62) | 23 (46.00) | 0.632 |
| Malar erythema, n (%) | 15 (46.88) | 20 (40.00) | 0.539 |
| Arthralgia, n (%) | 20 (62.50) | 32 (64.00) | 0.891 |
| Hair loss, n (%) | 17 (53.12) | 18 (36.00) | 0.126 |
| Mucosal ulcer, n (%) | 11 (34.38) | 10 (20.00) | 0.146 |
| Photosensitivity, n (%) | 5 (15.62) | 9 (18.00) | 0.780 |
| Raynaud’s phenomenon, n (%) | 5 (15.62) | 11 (22.00) | 0.477 |
| Urine occult blood, n (%) | 13 (40.62) | 11 (22.00) | 0.071 |
| Urine protein, n (%) | 19 (59.38) | 25 (50.00) | 0.406 |
| Pleurisy, n (%) | 13 (40.62) | 11 (22.00) | 0.071 |
| Pericarditis, n (%) | 9 (28.12) | 10 (20.00) | 0.395 |
| Antibodies | |||
| anti-dsDNA (+), n (%) | 12 (37.50) | 21 (42.00) | 0.770 |
| ANA (+), n (%) | 28 (87.50) | 48 (96.00) | 0.314 |
| anti-Sm (+), n (%) | 3 (9.38) | 12 (24.00) | 0.095 |
| anti-U1 RNP (+), n (%) | 10 (31.25) | 19 (38.00) | 0.533 |
| anti-SSA (+), n (%) | 12 (37.50) | 26 (52.00) | 0.199 |
| anti-SSB (+), n (%) | 2 (6.25) | 4 (8.00) | >0.999 |
2.3. 血清抗ENO1抗体结果
合并狼疮性视网膜病变组患者的血清抗ENO1抗体水平显著高于不合并视网膜病变组(16.11%±10.35% vs. 12.06%±6.47%，P=0.045)。SLE合并狼疮性视网膜病变组患者的抗ENO1抗体阳性例数为22例，SLE不合并狼疮性视网膜病变组患者的抗ENO1抗体阳性例数为23例，SLE合并狼疮性视网膜病变组患者的抗ENO1抗体阳性率显著高于不合并狼疮性视网膜病变组(68.75% vs. 46.00%，P=0.043)。
正常对照组抗ENO1抗体的阳性率为8.00%(4/50)，抗体水平(AU值)为6.09%±2.77%。SLE合并视网膜病变组的阳性率显著高于正常对照组(68.75% vs. 8.00%，P < 0.001)，SLE不合并视网膜病变组的阳性率也显著高于正常对照组(46.00% vs. 8.00%，P < 0.001)；SLE合并视网膜病变组的抗体水平(AU值)显著高于正常对照组(16.11%±10.35% vs. 6.09%±2.77%，P < 0.001)，SLE不合并视网膜病变组的抗体水平(AU值)也显著高于正常对照组(12.06%±6.47% vs. 6.09%±2.77%，P < 0.001)。
进一步比较抗ENO1抗体阳性与抗ENO1抗体阴性的SLE患者在临床表现与实验室相关指标之间的关系(表 3): 在临床表现上，抗ENO1抗体阳性与发热和尿潜血阳性有关的可能性大(P=0.011，P=0.042)；在实验室指标上，抗ENO1抗体阳性患者的ESR、IgA、IgG和PLT计数显著高于抗ENO1抗体阴性患者(P=0.001，P=0.014，P=0.000 3和P=0.008)。
表 3.
抗体阳性和抗体阴性患者的临床特点和实验室特点
Prevalence of symptoms and laboratory abnormalities of SLE patients
| Items | Anti-ENO1(+), n=45 | Anti-ENO1(-), n=37 | P value |
| SLEDAI, systemic lupus erythematosus disease activity index; Tmax, the highest temperature of the patients who had a fever during the disease; anti-dsDNA, anti-double stranded DNA antibody; ANA, antinuclear antibody; anti-U1 RNP, anti-U1 ribonucleoprotein antibody; anti-SSA, anti-Sjögren syndrome A antibody; anti-SSB, anti-Sjögren syndrome B antibody: ESR, erythrocyte sedimentation rate; CRP, C-reactive protein; IgA, immunoglobulin A; IgG, immunoglobulin G; IgM, immunoglobulin M; C3, complement 3; C4, complement 4; WBC, white blood cell count; HB, hemoglobin; PLT, blood platelet count. * P < 0.05, # P < 0.01. | |||
| SLEDAI-2000, x±s | 13.56±6.23 | 11.38±6.20 | 0.119 |
| Fever, n (%) | 26 (57.78) | 31 (83.78) | 0.011* |
| Tmax/℃, x±s | 38.88±0.69 | 38.96±0.79 | 0.705 |
| Rash, n (%) | 19 (42.22) | 17 (45.95) | 0.735 |
| Malar erythema, n (%) | 21 (46.67) | 14 (37.84) | 0.421 |
| Arthralgia, n (%) | 31 (68.89) | 21 (56.76) | 0.256 |
| Hair loss, n (%) | 20 (44.44) | 15 (40.54) | 0.722 |
| Mucosal ulcer, n (%) | 9 (20.00) | 12 (32.43) | 0.199 |
| Photosensitivity, n (%) | 6 (13.33) | 8 (21.62) | 0.301 |
| Raynaud’s phenomenon, n (%) | 9 (20.00) | 7 (18.92) | 0.902 |
| Urine occult blood, n (%) | 9 (20.00) | 15 (40.54) | 0.042* |
| Urine protein, n (%) | 12 (46.67) | 23 (62.16) | 0.161 |
| Pleurisy, n (%) | 14 (31.11) | 10 (27.03) | 0.686 |
| Pericarditis, n (%) | 11 (24.44) | 8 (21.62) | 0.763 |
| Anti-dsDNA (+), n (%) | 21 (47.73) | 12 (32.43) | 0.163 |
| ANA (+), n (%) | 44 (97.78) | 32 (86.49) | 0.127 |
| anti-Sm (+), n (%) | 11 (24.44) | 4 (10.81) | 0.112 |
| anti-U1 RNP (+), n (%) | 19 (42.22) | 10 (27.03) | 0.152 |
| anti-SSA (+), n (%) | 21 (46.67) | 17 (45.95) | 0.948 |
| anti-SSB (+), n (%) | 6 (13.33) | 0 | 0.060 |
| ESR/(mm/h), M (range) | 29.50 (1.52－110.00) | 12.00 (4.00－101.00) | 0.001# |
| CRP/(mg/L), M (range) | 1.30 (0.30－52.40) | 1.55 (0.39－101.71) | 0.922 |
| IgA/(g/L), M (range) | 2.85 (0.07－27.00) | 2.05 (0.42－4.36) | 0.014* |
| IgG/(g/L), M (range) | 14.30 (4.02－37.80) | 10.46 (2.50－25.73) | 0.0003# |
| IgM/(g/L), M (range) | 0.90 (0.22－3.18) | 0.69 (0.17－2.24) | 0.148 |
| C3/(g/L), x±s | 0.63±0.31 | 0.73±0.29 | 0.157 |
| C4/(g/L), M (range) | 0.14 (0.02－0.47) | 0.16 (0.02－0.49) | 0.245 |
| WBC/(×109 /L), M (range) | 6.40 (1.89－12.20) | 5.00 (1.50－17.60) | 0.132 |
| HB/(g/L), x±s | 107.98±19.09 | 111.32±23.76 | 0.481 |
| PLT/(×109 /L), x±s | 205.87±67.98 | 164.57±69.57 | 0.008# |
3. 讨论
SLE是一种累及多系统多脏器的自身免疫病，狼疮性血管病变是其典型病理学特征之一[14]，也是SLE患者发病率高和病死率高的主要原因之一[15]。狼疮性血管病变可发生于皮肤和内脏，主要表现包括皮肤血管炎、神经精神狼疮(非炎症性微血管病)、肠系膜血管炎、股骨头坏死、周围神经病、肾小血管炎、弥漫性肺泡出血、冠状动脉血管炎以及视网膜血管炎[15-17]。狼疮性血管炎最常见发生于小血管，中型血管也可受累，大血管受累比较少见[18]，炎症反应通常发生于血管局部，受损血管和正常血管间隔分布[16]。既往研究认为狼疮性血管炎的发生原因是补体激活引起免疫复合物沉积，以及自身抗体导致内皮破坏、炎性细胞浸润，最终血管壁坏死[17]。自身抗体包括抗内皮细胞抗体、抗磷脂抗体、抗dsDNA抗体等，另外，抗ENO1抗体也可以造成内皮损伤[19]。
抗ENO1抗体对应的抗原为α烯醇化酶(α-enolase), 烯醇化酶是一种糖酵解酶，有α，β和γ三种亚型[20]。α烯醇化酶由ENO1基因编码，相对分子质量为46 000~48 000[12, 20-21]，是一种广泛存在的多功能蛋白，在真核细胞的细胞膜上作为纤溶酶原受体调节纤溶活性[22]。抗ENO1抗体阻碍α烯醇化酶和纤溶酶原的结合，中断血管内和细胞周围的纤溶系统，导致细胞凋亡[19]，引起内皮损伤。已有实验检测到抗ENO1抗体存在于狼疮肾炎(lupus nephritis, LN)、神经精神狼疮、狼疮性肌炎、狼疮性皮肤血管炎，以及SLE继发的浆膜炎患者的外周血血清中[23-30]。
除了上述细胞膜上的表达，α烯醇化酶还定位于胞质内。胞质内的α烯醇化酶主要存在于视网膜光感受器细胞外节、缪勒(Müller)细胞和神经节细胞层[12-13]，主要功能是参与糖酵解途径产生ATP的过程，催化甘油酸-2-磷酸转化为磷酸烯醇式丙酮酸[23-24]。抗α烯醇化酶抗体被认为是一种视网膜自身抗体(anti-retinal antibody, ARA)，结合α烯醇化酶后使其不能发挥催化功能，阻断糖酵解过程产生ATP，导致细胞缺氧，胞浆内Ca2+浓度升高，最终导致细胞凋亡[24]。因此，抗ENO1抗体可引起视网膜感光细胞、Müller细胞和节细胞的凋亡。本研究发现在SLE患者中，合并狼疮性视网膜病变患者的抗ENO1抗体的阳性率和水平显著高于不合并视网膜病变组，但两组之间其他全身临床表现及SLE活动性相关的一些实验室指标的差异均无统计学意义，提示该抗体可能在视网膜病变的诊断方面具有一定的特异性。
狼疮性视网膜病变是评价SLE疾病活动性的一个重要指标，本研究发现合并狼疮性视网膜病变患者的SLEDAI-2000评分显著高于不合并视网膜病变组。既往研究发现狼疮性视网膜病变患者的一种视网膜自身抗体——抗recoverin抗体水平和SLE疾病活动度、IgG和ESR呈正相关[3]，抗恢复蛋白抗体是一种只在视网膜内外层有定位的视网膜自身抗体，可导致视网膜细胞凋亡[25]。而本研究比较了另一种视网膜自身抗体——抗ENO1抗体阳性和阴性的SLE患者的临床和实验室特征，发现抗体阳性患者的ESR、血清IgA、血清IgG和PLT显著升高。因此，抗ENO1抗体阳性提示该患者有更高的疾病活动度，推测该抗体可能作为狼疮性视网膜病变的活动性指标。
综上所述，抗ENO1抗体作为一种可以造成血管内皮损伤和视网膜神经细胞凋亡的视网膜自身抗体，可能与狼疮性视网膜病变的发病相关，合并狼疮性视网膜病变的SLE患者血清中抗ENO1抗体的水平和阳性率明显升高，且具有更高的疾病活动性。
Funding Statement
国家重点研发计划项目(2020YFC20820)和首都临床诊疗技术研究及示范应用项目(Z191100006619029)
Supported by the National Key Research and Development Program of China (2020YFC200820) and the Capital Clinical Diagnosis and Treatment Technology Research and Demonstration Application Project of China (Z191100006619029)
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