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Journal of Peking University (Health Sciences) ›› 2023, Vol. 55 ›› Issue (6): 958-965. doi: 10.19723/j.issn.1671-167X.2023.06.002

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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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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

CLC Number: 

  • R593.2

Figure 1

Disease distribution in patients with positive anti-Jo-1 antibody ASS, anti-synthetase syndrome; IMNM, immune-mediated necrotizing myositis; DM, dermatomyositis; RA, rheumatoid arthritis; UCTD, undifferentiated connective tissue disease; IPAF, interstitial pneumonia with autoimmune features; UA, undifferentiated arthritis; SS, Sjögren's syndrome; SLE, systemic lupus erythematosus; SV, systemic vasculitis; SSc, systemic sclerosis; APS, antiphospholipid syndrome; PMR, polymyalgia rheumatica; Non-CTD, non-connective tissue disease."

Table 1

Comparison of clinical features and laboratory data in ASS with positive and negative anti-Jo-1 antibody"

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

Figure 2

The top five diseases with high, median and low anti-Jo-1 antibody titer Abbreviations as in Figure 1 and Table 1."

Table 2

Correlation analysis between anti-Jo-1 antibody titer and clinical features and laboratory data of ASS patients"

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

Table 3

Comparison of clinical features and laboratory data in ASS patients with positive anti-Jo-1 antibody only and ASS patients positive for anti-Jo-1 antibody combined with other MAAs/MSAs"

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

Figure 3

Condition of anti-Jo-1 antibody with anti-Ro-52, anti-PM-Scl 75/100 and ANA in IIM patients The red part represents the anti-Jo-1 antibody-positive samples, the blue part represents the anti-Ro-52 antibody-positive samples, the purple part represents the anti-PM-Scl 75/100 antibody-positive samples, the green part represents the antinuclear antibody-positive samples, and the overlap part represents the patients with two or more positive antibodies at the same time."

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