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北京大学学报（医学版） ›› 2023, Vol. 55 ›› Issue (6): 958-965. doi: 10.19723/j.issn.1671-167X.2023.06.002

• 论著 • 上一篇    下一篇

抗Jo-1抗体在特发性炎性肌病临床分层及疾病谱中的意义

李嘉辰1,赖展鸿1,邵苗1,金月波1,高小娟2,张科3,侯儆4,张燕英5,栗占国1,*(),李玉慧1,*()   

  1. 1. 北京大学人民医院风湿免疫科, 北京 100044
    2. 宁德师范学院附属宁德市医院风湿免疫科, 福建宁德 352199
    3. 中国人民解放军第80集团军医院内分泌科, 山东潍坊 261000
    4. 张家口市第一医院肾内科, 河北张家口 075041
    5. 深圳市中医院风湿病科, 深圳 518033
  • 收稿日期:2023-08-19 出版日期:2023-12-18 发布日期:2023-12-11
  • 通讯作者: 栗占国,李玉慧 E-mail:li99@bjmu.edu.cn;liyuhui84@163.com
  • 基金资助:
    国家自然科学基金(82371804);北京市自然科学基金海淀原始创新联合基金项目(L222017);北京大学人民医院研究与发展基金(RDX2023-03)

Significance of anti-Jo-1 antibody's clinical stratification in idiopathic inflammatory myopathy and disease spectrum

Jia-chen LI1,Zhan-hong LAI1,Miao SHAO1,Yue-bo JIN1,Xiao-juan GAO2,Ke ZHANG3,Jing HOU4,Yan-ying ZHANG5,Zhan-guo LI1,*(),Yu-hui LI1,*()   

  1. 1. Department of Rheumatology and Immunology, Peking University People's Hospital, Beijing 100044, China
    2. Department of Rheumatology and Immunology, Ningde Hospital Affiliated to Ningde Normal University, Ningde 352199, Fujian, China
    3. Department of Endocrinology, 80th Group Army Hospital of Chinese PLA, Weifang 261000, Shandong, China
    4. Department of Nephrology, Zhangjiakou First Hospital, Zhangjiakou 075041, Hebei, China
    5. Department of Rheumatology, Shenzhen Hospital of Traditional Chinese Medicine, Shenzhen 518033, China
  • Received:2023-08-19 Online:2023-12-18 Published:2023-12-11
  • Contact: Zhan-guo LI,Yu-hui LI E-mail:li99@bjmu.edu.cn;liyuhui84@163.com
  • Supported by:
    the National Natural Science Foundation of China(82371804);Beijing Natural-Science Foundation(L222017);Peking University People's Hospital Research and Development Foundation(RDX2023-03)

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摘要：

目的: 探究抗组氨酰tRNA合成酶(histidyl tRNA synthetase，Jo-1)抗体在特发性炎性肌病(idiopathic inflammatory myopathies，IIM)及其他疾病谱的意义。方法: 入组北京大学人民医院2016—2022年利用免疫印迹法检测抗Jo-1抗体阳性的患者，同时入组抗Jo-1抗体阴性的抗合成酶综合征(anti-synthetase syndrome，ASS)患者作为对照，分析患者的基本信息、临床特征以及炎症和免疫学指标。结果: 共入组165例抗Jo-1抗体阳性患者，结缔组织病(connective tissue disease，CTD)占80.6%(133/165)，其中IIM占总数的57.6%(95/165)，包括ASS(84/165，50.9%)、免疫介导坏死性肌病(7/165，4.2%)以及皮肌炎(4/165，2.4%)，其他CTD占23.0%(38/165)，包括类风湿关节炎(11/165，6.7%)、未分化结缔组织病(5/165, 3.0%)、具有自身免疫特征的间质性肺炎(5/165，3.0%)、未分化关节炎(4/165，2.4%)、干燥综合征(3/165，1.8%)、系统性红斑狼疮(3/165，1.8%)和系统性血管炎(3/165，1.8%)等；其他疾病包括恶性肿瘤(3/165，1.8%)和感染(4/165，2.4%)等；未明确诊断患者占9.1%(15/165)。在ASS亚组分析中，抗Jo-1抗体阳性的ASS患者相比于抗体阴性者起病年龄更低(49.9岁vs. 55.0岁，P=0.026)，更多表现为关节炎(60.7% vs. 33.3%，P=0.002)和肌痛(47.1% vs. 22.2%，P=0.004)。ASS患者随着抗Jo-1抗体滴度的升高，关节炎、技工手、Gottron征、雷诺现象(Raynaud phenomenon)以及肌酸激酶、α-羟丁酸脱氢酶指标异常的发生率升高。抗Jo-1抗体阳性ASS患者在合并一种以上其他肌炎抗体阳性时，肌痛、肌无力的发生率升高(P < 0.05)。结论: 抗Jo-1抗体阳性患者疾病谱广，以ASS为主，但也可见于其他CTD、肿瘤、感染等疾病，应注意鉴别。

关键词: 抗组氨酰tRNA合成酶抗体, 抗合成酶综合征, 结缔组织病

Abstract:

Objective: To investigate the significance of anti-histidyl tRNA synthetase (Jo-1) antibody in idiopathic inflammatory myopathies (IIM) and its diseases spectrum. Methods: We enrolled all the patients who were tested positive for anti-Jo-1 antibody by immunoblotting in Peking University People's Hospital between 2016 and 2022. And the patients diagnosed with anti-synthetase antibody syndrome (ASS) with negative serum anti-Jo-1 antibody were enrolled as controls. We analyzed the basic information, clinical characteristics, and various inflammatory and immunological indicators of the patients at the onset of illness. Results: A total of 165 patients with positive anti-Jo-1 antibody were enrolled in this study. Among them, 80.5% were diagnosed with connective tissue disease. And 57.6% (95/165) were diagnosed with IIM, including ASS (84/165, 50.9%), immune-mediated necrotizing myopathy (7/165, 4.2%) and dermatomyositis (4/165, 2.4%). There were 23.0% (38/165) diagnosed with other connective tissue disease, mainly including rheumatoid arthritis (11/165, 6.7%), undifferentiated connective tissue disease (5/165, 3.0%), interstitial pneumonia with autoimmune features (5/165, 3.0%), undifferentiated arthritis (4/165, 2.4%), Sjögren's syndrome (3/165, 1.8%), systemic lupus erythematosus (3/165, 1.8%), systemic vasculitis (3/165, 1.8%), and so on. Other cases included 3 (1.8%) malignant tumor patients, 4 (2.4%) infectious cases and so on. The diagnoses were not clear in 9.1% (15 /165) of the cohort. In the analysis of ASS subgroups, the group with positive serum anti-Jo-1 antibody had a younger age of onset than those with negative serum anti-Jo-1 antibody (49.9 years vs. 55.0 years, P=0.026). Clinical manifestations of arthritis (60.7% vs. 33.3%, P=0.002) and myalgia (47.1% vs. 22.2%, P=0.004) were more common in the ASS patients with positive anti-Jo-1 antibody. With the increase of anti-Jo-1 antibody titer, the incidence of the manifestations of arthritis, mechanic hands, Gottron sign and Raynaud phenomenon increased, and the proportion of abnormal creatine kinase and α-hydroxybutyric dehydrogenase index increased in the ASS patients. The incidence of myalgia and myasthenia were significantly more common in this cohort when anti-Jo-1 antibody-positive ASS patients were positive for one and more myositis specific antibodies/myositis associated autoantibodies (P < 0.05). Conclusion: The disease spectrum in patients with positive serum anti-Jo-1 antibody includes a variety of diseases, mainly ASS. And anti-Jo-1 antibody can also be found in many connective tissue diseases, malignant tumor, infection and so on.

Key words: Anti-histidyl tRNA synthetase antibody, Anti-synthetase syndrome, Connective tissue disease

中图分类号: 

  • R593.2

图1

抗Jo-1抗体阳性患者疾病分布"

表1

抗Jo-1抗体阳性与阴性ASS患者临床特征及实验室数据对比"

Items Anti-Jo-1 (+) (n=84) Anti-Jo-1 (-) (n=45) t/Z/χ2 P
Clinical features
  Age of onset/years 49.9±12.8 55.0±11.9 2.247 0.026
  Female 64 (76.2) 33 (73.3) 0.128 0.720
  ILD 72 (85.7) 43 (95.6) 2.933 0.087
  Arthritis 51 (60.7) 15 (33.3) 8.792 0.003
  Myalgia 40 (47.1) 10 (22.2) 7.962 0.005
  Myasthenia 45 (53.6) 21 (46.7) 0.559 0.455
  Dysphagia 5 (6.0) 6 (13.3) 2.047 0.153
  Mechanic hands 45 (53.6) 23 (51.1) 0.071 0.790
  Gottron sign 68 (81.0) 39 (86.7) 0.676 0.411
  Raynaud phenomenon 11 (13.1) 8 (17.8) 0.842 0.474
  Neurologic abnormality 4 (4.8) 0 0.297a
  Malignancy 2 (2.4) 1 (2.2) >0.999a
Laboratory data
  ANA+ 44 (52.4) 29 (64.4) 1.736 0.188
  Anti-Ro-52 (+) 63 (75.0) 36 (80.0) 0.410 0.522
  Anti-PM-Scl 75/100 (+) 5 (6.0) 0 0.156a
  Anti-Mi-2 (+) 2 (2.4) 1 (2.2) >0.999a
  Anti-SAE (+) 1 (1.2) 0 >0.999a
  Anti-MDA5 (+) 1 (1.2) 0 >0.999a
  Anti-NXP2 (+) 0 0
  Anti-TIF-1γ (+) 0 1 (2.2) 0.349a
  Anti-SRP (+) 1 (1.2) 0 >0.999a
  ESR/(mm/h) 20.0 (8.0, 44.0) 32.0 (16.0, 58.0) -2.067 0.039
  Elevated ESR 42 (50.0) 32 (71.1) 5.340 0.021
  CRP/(mg/L) 4.3 (0.6, 27.0) 13.2 (1.5, 27.0) -1.648 0.099
  Elevated CRP 51 (60.7) 24 (53.3) 0.656 0.418
  CK/(U/L) 230.0 (93.0, 1 059.0) 131.0 (69.0, 413.0) -1.733 0.083
  Elevated CK 46 (54.8) 19 (42.2) 1.843 0.175

图2

抗Jo-1抗体滴度与疾病分布(前五种)"

表2

抗Jo-1抗体滴度与ASS患者临床特征及实验室数据的相关性分析"

Items Anti-Jo-1 (+) (n=15) Anti-Jo-1 (++) (n=15) Anti-Jo-1 (+++)(n=54) r P
Clinical features
  Fever 5 (33.3) 4 (26.7) 9 (16.7) -0.163 0.140
  ILD 12 (80.0) 13 (86.7) 47 (87.0) 0.062 0.576
  Arthritis 4 (26.7) 7 (46.7) 40 (74.1) 0.385 < 0.001
  Myalgia 6 (40.0) 11 (73.3) 24 (44.4) -0.071 0.521
  Myasthenia 6 (40.0) 8 (53.3) 32 (59.3) 0.136 0.218
  Dysphagia 0 0 5 (9.3) 0.183 0.096
  Mechanic hands 4 (26.7) 8 (53.3) 33 (61.1) 0.233 0.033
  Raynaud phenomenon 0 1 (2.6) 10 (15.2) 0.223 0.041
  Gottron sign 9 (60.0) 12 (80.0) 47 (87.3) 0.236 0.031
  Malignancy 1 (6.7) 0 1 (1.9) -0.074 0.504
  Neurologic abnormality 1 (6.7) 0 3 (5.6) 0.028 0.797
Laboratory data
  Elevated WBC 7 (46.7) 10 (66.7) 38 (70.4) 0.162 0.141
  Decreased lymphocyte 8 (53.3) 9 (60.0) 31 (57.4) 0.016 0.887
  Elevated neutrophil 10 (66.7) 11 (73.3) 38 (70.4) 0.013 0.905
  Elevated ESR 7 (46.7) 4 (26.7) 31 (57.4) 0.159 0.151
  Elevated CRP 7 (46.7) 1 (6.7) 24 (44.4) 0.087 0.445
  Decreased albumin 13 (86.7) 10 (66.7) 40 (74.1) -0.058 0.600
  Elevated CK 4 (26.7) 8 (53.3) 34 (63.0) 0.263 0.016
  Elevated LDH 13 (86.7) 10 (66.7) 43 (79.6) 0.002 0.958
  Elevated α-HBD 10 (66.7) 9 (60.0) 47 (87.0) 0.255 0.021

表3

单一抗Jo-1抗体与抗Jo-1抗体合并其他MAAs/MSAs阳性ASS患者临床特征及实验室数据对比"

Items Isolated anti-Jo-1 (+)
(n=20)		 Coexistence of anti-Jo-1 (+) and MAAs/MSAs (+)
(n=64)		 t/Z/χ2 P
Clinical features
  Age of onset/years 45.60±10.15 49.94±13.60 -0.102 0.919
  Female 15 (75.0) 49 (76.6) < 0.001 >0.999
  Fever 5 (25.0) 13 (20.3) 0.018 0.894
  Myalgia 5 (25.0) 36 (56.3) 5.956 0.015
  Myasthenia 7 (35.0) 39 (61.0) 4.138 0.042
  Dysphagia 0 5 (7.8) 0.332a
  Gottron sign 15 (75.0) 53 (82.8) 0.203 0.652
  Raynaud phenomenon 2 (10.0) 9 (14.1) 0.008 0.928
  ILD 17 (85.0) 55 (85.9) < 0.001 >0.999
  Mechanic hands 9 (45.0) 36 (56.3) 0.775 0.379
  Arthritis 11 (55.0) 40 (62.5) 0.359 0.549
  Neurologic abnormality 1 (5.0) 3 (4.7) >0.999a
  Malignancy 1 (5.0) 1 (1.6) 0.422a
Laboratory data
  ESR/(mm/h) 15.5 (7.5, 31.5) 22.0 (8.0, 56.0) -1.076 0.282
  Elevated ESR 9 (45.0) 33 (51.6) 0.331 0.565
  CRP/(mg/L) 7.1 (0.5, 12.4) 4.3 (0.6, 32.2) -0.952 0.341
  Elevated CRP 8 (40.0) 24 (37.5) 0.046 0.836
  CK/(U/L) 155.0 (80.0, 756.0) 237.0 (100.0, 1153.0) -0.799 0.425
  Elevated CK 10 (50.0) 36 (56.3) 0.313 0.576

图3

IIM患者中抗Jo-1抗体与抗Ro-52抗体、抗PM-Scl 75/100抗体及抗核抗体合并存在情况"

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