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北京大学学报（医学版） ›› 2022, Vol. 54 ›› Issue (6): 1099-1105. doi: 10.19723/j.issn.1671-167X.2022.06.007

• 论著 • 上一篇    下一篇

抗ENO1抗体与狼疮性视网膜病变的相关性

张琳崎1,赵静2,王红彦2,王宗沂1,李英妮2,汤稷旸1,李思莹1,曲进锋1,*(),赵明威1   

  1. 1. 北京大学人民医院眼科、眼视光中心，眼病与视光医学研究所，视网膜脉络膜疾病诊治研究北京市重点实验室，北京大学医学部眼视光学院，北京 100044
    2. 北京大学人民医院风湿免疫科，北京 100044
  • 收稿日期:2022-08-19 出版日期:2022-12-18 发布日期:2022-12-19
  • 通讯作者: 曲进锋 E-mail:drbari@163.com
  • 基金资助:
    国家重点研发计划项目(2020YFC20820);首都临床诊疗技术研究及示范应用项目(Z191100006619029)

Relationship between anti-ENO1 antibody and systemic lupus erythematosus patients with retinopathy

Lin-qi ZHANG1,Jing ZHAO2,Hong-yan WANG2,Zong-yi WANG1,Ying-ni LI2,Ji-yang TANG1,Si-ying LI1,Jin-feng QU1,*(),Ming-wei ZHAO1   

  1. 1. Department of Ophthalmology, Peking University People's Hospital, Eye Diseases and Optometry Institute, Beijing Key Laboratory of Diagnosis and Therapy of Retinal and Choroid Disease, College of Optometry, Peking University Health and Science Center, Beijing, 100044
    2. Department of Rheumatology and Immunology, Peking University People's Hospital, Beijing, 100044
  • Received:2022-08-19 Online:2022-12-18 Published:2022-12-19
  • Contact: Jin-feng QU E-mail:drbari@163.com
  • Supported by:
    the National Key Research and Development Program of China(2020YFC20820);the Capital Clinical Diagnosis and Treatment Technology Research and Demonstration Application Project of China(Z191100006619029)

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摘要：

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。

关键词: 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.

Key words: Systemic lupus erythematosus, Retinopathy, Autoantibody, α-enolase, Anti-ENO1 antibody

中图分类号: 

  • R593.24

表1

受试者人口学资料比较"

Items SLE retinopathy SLE without retinopathy Healthy control P value
Age/years, ${\bar x}$±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 - -

表2

两组SLE患者的临床特点和实验室指标"

Items SLE retinopathy, n=32 SLE without retinopathy, n=50 P value
SLEDAI-2000, ${\bar x}$±s 17.41±4.25 9.48±5.35 < 0.001#
Clinical Features
  Fever, n (%) 22 (68.75) 35 (70.00) 0.905
  Tmax/℃, ${\bar x}$±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

表3

抗体阳性和抗体阴性患者的临床特点和实验室特点"

Items Anti-ENO1(+), n=45 Anti-ENO1(-), n=37 P value
SLEDAI-2000, ${\bar x}$±s 13.56±6.23 11.38±6.20 0.119
Fever, n (%) 26 (57.78) 31 (83.78) 0.011*
Tmax/℃, ${\bar x}$±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), ${\bar x}$±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), ${\bar x}$±s 107.98±19.09 111.32±23.76 0.481
PLT/(×109 /L), ${\bar x}$±s 205.87±67.98 164.57±69.57 0.008#
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ISSN 1671-167X
CN 11-4691/R
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