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北京大学学报（医学版） ›› 2024, Vol. 56 ›› Issue (6): 980-986. doi: 10.19723/j.issn.1671-167X.2024.06.006

• 论著 • 上一篇    下一篇

抗EJ抗体阳性抗合成酶综合征相关间质性肺疾病复发的临床特征分析

朱玉静, 王磊, 吕成银, 谈文峰, 张缪佳*()   

  1. 南京医科大学第一附属医院风湿免疫科，南京 210029
  • 收稿日期:2024-08-01 出版日期:2024-12-18 发布日期:2024-12-18
  • 通讯作者: 张缪佳 E-mail:miaojia_zhang@163.com
  • 基金资助:
    南京医科大学第一附属医院临床能力提升工程(JSPH-MC-2023-29)

Analysis of clinical features of ruccrent interstitial lung disease in patients with anti-EJ positive antisynthetase syndrome

Yujing ZHU, Lei WANG, Chengyin LYU, Wenfeng TAN, Miaojia ZHANG*()   

  1. Department of Rheumatology and Immunology, the First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China
  • Received:2024-08-01 Online:2024-12-18 Published:2024-12-18
  • Contact: Miaojia ZHANG E-mail:miaojia_zhang@163.com
  • Supported by:
    the Clinical Capacity Enhancement Project of the First Affiliated Hospital of Nanjing Medical University(JSPH-MC-2023-29)

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摘要：

目的: 总结57例抗EJ (anti-glycyl tRNA synthetase) 抗体阳性抗合成酶综合征(antisynthetase syndrome, ASS) 相关间质性肺疾病(interstitial lung disease, ILD) 患者的临床特征，并分析ILD复发的相关因素。方法: 选择2020年1月1日至2024年6月30日在南京医科大学第一附属医院(江苏省人民医院)风湿免疫科就诊的57例抗EJ抗体阳性ASS患者的病例资料进行回顾性分析，收集的数据包括患者的一般情况、临床表现、实验室检查结果和胸部CT影像，以及肺功能检查结果[包括用力肺活量(forced vital capacity, FVC)、第1秒用力呼气容积(forced expiratory volume in the first second, FEV1) 和一氧化碳弥散量(diffusion lung carbon monoxide, DLCO)]，并进一步分析ILD复发的临床特征。结果: 所有57例抗EJ抗体阳性ASS患者均合并ILD，平均发病年龄为(58.18±10.27)岁，平均病程为3.00 (2.00, 16.00)个月。患者中70. 18%为女性，87.72%有咳嗽症状，70. 18%有咳痰症状，89.47%出现呼吸困难，14.04%发生呼吸衰竭。肺功能结果显示，FVC占正常预计值的百分比(FVC%)、FEV1占正常预计值的百分比(FEV1%) 和DLCO占正常预计值的百分比(DLCO%) 分别为59.36±21.41、58.34±19.46和58.17±27.95，氧合指数为(363.24±99.42) mmHg。胸部CT影像中，非特异性间质性肺炎(nonspecific interstitial pneumonia, NSIP) 为最常见的影像学表现类型。在46例完成12个月以上随访的患者中，21例(45.65%) 出现了ILD复发。复发组的平均发病年龄为(61.38±8.63)岁，而非复发组为(55.28±11.85)岁，差异无统计学意义(P=0.056)。进一步分析发现，复发组的红细胞沉降率(erythrocyte sedimentation rate, ESR) 水平显著高于非复发组[(50.48±29.64) mm/h vs. 30.28±23.97) mm/h, P=0.025]，血清IgM (immune globulin M, IgM) 水平也明显高于非复发组(P=0.042)。此外，复发组的CD8 + T细胞百分比显著高于非复发组(25.48±11.81 vs. 18.59± 8.53, P=0.027)。尽管复发组患者在基线时的年龄偏大，且ESR、IgM和CD8 + T细胞百分比在两组间差异有统计学意义，但多因素二元Logistics回归分析显示，这些指标均未被证实为ILD复发的独立危险因素。结论: ILD是抗EJ抗体阳性ASS患者的主要临床表现，并且常伴有显著的肺功能损伤。尽管糖皮质激素和免疫抑制剂的联合治疗对大多数患者有效，但ILD的复发率依然较高。基线ESR水平增快、IgM升高及CD8+ T细胞百分比增加的患者更容易出现复发。

关键词: 抗合成酶综合征, 间质性肺疾病, 抗甘氨酸基tRNA合成酶抗体, 复发

Abstract:

Objective: To summarize the clinical characteristics of 57 patients diagnosed with anti-glycyl tRNA synthetase (anti-EJ) positive antisynthetase syndrome (ASS), a subtype of anti-glycyl tRNA positive ASS, complicated by interstitial lung disease (ILD), and to investigate the factors asso-ciated with ILD recurrence. Methods: A retrospective analysis was conducted on the clinical data of 57 anti-EJ positive ASS patientswho were treated at the First Affiliated Hospital of Nanjing Medical University from January 1, 2020 to June 30, 2024. The data collected included demographic information, clinical characteristics, laboratory test results, chest CT findings, and pulmonary function tests. The characteristics of ILD recurrence were also analyzed. Results: All the 57 patients with anti-EJ positive ASS were diagnosed with ILD. The mean age at disease onset was (58.18±10.27) years, with a mean disease duration of 3.00 (2.00, 16.00) months. Among the patients, 70. 18% were female, 87.72% experienced a cough, 70. 18% had expectoration, 89.47% reported respiratory difficulties, and 14.04% developed respiratory failure. The results of pulmonary function test showed that the percentage of forced vital capacity (FVC) in the normal predicted value (FVC%), the percentage of forced expiratory volume in the first second (FEV1) in the normal predicted value (FEV1%) and the percentage of diffusion lung carbon monoxide (DLCO) in the normal predicted value (DLCO%) were 59.36±21.41, 58.34±19.46 and 58.17±27.95, respectively. The oxygenation index was (363.24±99.42) mmHg. Chest CT imaging showed that nonspecific interstitial pneumonia (NSIP) was the most common radiographic pattern. Among the 46 patients who completed a follow-up of more than 12 months, 21 cases (45.65%) showed recurrence of ILD. The average age of onset for the recurrence group was (61.38±8.63) years, while that for the non-recurrence group was (55.28±11.85) years, with a difference approaching statistical significance (P=0.056). Further analysis showed that the ESR (erythrocyte sedimentation rate) level was significantly higher in the recurrence group than in the non-recurrence group [(50.48±29.64) mm/h vs. 30.28±23.97) mm/h, P=0.025], and the IgM (immune globulin M) level was also significantly higher in the recurrence group (P=0.042). Moreover, the CD8+T proportion was significantly higher in the recurrence group than in the non-recurrence group (25.48±11.81 vs. 18.59± 8.53, P=0.027). Despite the fact that the recurrence group had a higher baseline age, higher ESR, IgM, and CD8+T proportion, multivariate binary logistic regression analysis showed that these indicators were not independent risk factors for ILD recurrence. Conclusion: ILD is the most common clinical manifestation in patients with anti-EJ positive ASS, with a significant impact on pulmonary function. Although the patients responded well to a combination of glucocorticoid and immunosuppressive therapies, the recurrence rate remains high, particularly in those with increased sputum production, and elevated ESR. Close monitoring and early intervention for high-risk patients are essential to improving long-term outcomes.

Key words: Antisynthetase syndrome, Interstitial lung disease, anti-glycyl tRNA antisynthetase antibody, Recurrence

中图分类号: 

  • R563

图1

临床资料分析流程图"

表1

抗EJ抗体阳性ASS-ILD复发组和非复发组基线临床表现比较"

Clinical parameters Overall (n=57) Ruccrence (n=21) Non-ruccrence (n=25) P
Female 40 (70.18) 17 (80.95) 18 (72.00) 0.514
Age/years 58.18±10.27 61.38±8.63 55.28±11.85 0.056
ILD diagnosis time/months 3.00 (2.00, 16.00) 3.00 (2.00, 10.00) 2.50 (1.75, 24.00) 0.461
Cough 50 (87.72) 20 (95.24) 21 (84.00) 0.351
Sputum 40 (70.18) 18 (85.71) 15 (60.00) 0.099
Dyspnea 51 (89.47) 19 (90.48) 23 (92.00) 1.000
Respiratory failure 8 (14.04) 2 (9.52) 3 (12.00) 1.000
Fever 13 (22.81) 3 (14.29) 7 (28.00) 0.306
Mechanic’s hands 16 (28.07) 5 (23.81) 7 (28.00) 1.000
DM rash 16 (28.07) 6 (28.57) 9 (36.00) 0.754
Myocardial injury 14 (24.56) 6 (28.57) 8 (32.00) 1.000
Myalgia 20 (35.09) 4 (19.05) 7 (28.00) 0.514
Arthritis 11 (19.30) 5 (23.81) 4 (16.00) 0.711
Ro-52 51 (89.47) 18 (85.71) 23 (92.00) 0.648
Treatment (baseline)
TAC 30 (52.63) 11 (52.38) 14 (56.00) 1.000
CYC 15 (26.32) 5 (23.81) 6 (24.00) 1.000
MMF 4 (7.18) 4 (19.05) 0 (0.00) 0.024
Glucocorticoid dosage/(mg/d) 63.68±45.73 72.14±50.01 53.40±28.32 0.118

表2

抗EJ抗体阳性ASS-ILD复发组和非复发组基线实验室指标及肺功能比较"

Category Overall (n=57) Ruccrence (n=21) Non-ruccrence (n=25) P
WBC/(×109/L) 8.40±4.21 9.74±3.67 8.78±3.17 0.346
lymphocyte count/(×109/L) 1.42±0.87 1.34±0.60 1.56±1.13 0.423
ESR/(mm/h) 40.63±27.80 50.48±29.64 30.28±23.97 0.014
CRP/(mg/L) 12.77±16.48 12.74±14.96 9.85±12.33 0.476
SF/(μg/L) 302.34±253.00 282.96±215.12 256.89±184.98 0.665
CK/(U/L) 80.00 (32.00, 375.50) 45.00 (24.50, 78.00) 238.50 (32.50, 1 291.50) 0.428
LDH/(U/L) 292.00 (245.50, 378.00) 271.00 (244.50, 277.75) 368.00 (269.75, 419.75) 0.275
IgG/(g/L) 12.40 (9.86, 15.20) 11.35 (10.83, 13.13) 13.05 (10.33, 22.73) 0.193
IgM/(g/L) 1.87 (1.17, 3.06) 2.02 (1.62, 3.68) 1.68 (0.98, 2.85) 0.042
IgA/(g/L) 2.64±1.07 2.57±1.20 2.73±1.06 0.626
CD3+ T/% 61.17±12.41 59.98±17.00 61.77±9.33 0.654
CD4+ T/% 39.26±11.43 36.23±12.55 41.6±10.75 0.125
CD8+ T/% 21.36±10.38 25.48±11.81 18.59±8.53 0.027
Oxygen index/mmHg 363.24±99.42 360.69±99.58 386.11±106.34 0.477
FVC% 59.36±21.41 60.45±25.13 64.71±17.38 0.578
FEV1% 58.34±19.46 58.05±21.49 64.07±16.83 0.381
DLCO% 58.17±27.95 60.67±32.52 56.78±22.61 0.694

表3

21例复发患者基线和复发时实验室指标比较"

Category Baseline Ruccrence P
WBC/(×109/L) 9.74±3.67 9.55±3.21 0.797
lymphocyte count/(×109/L) 1.34±0.50 1.20±0.62 0.462
Neutrophils count/(×109/L) 7.66±3.49 7.72±3.03 0.928
Hb/(g/L) 123.33±13.44 128.67±11.70 0.925
PLT/(×109/L) 269.95±77.29 258.17±69.44 0.422
CK/(U/L) 82.00 (45.00, 216.50) 93.00 (35.00, 134.00) 0.068
LDH/(U/L) 342.95±135.26 287.24±91.68 0.095
SF/(μg/L) 248.50 (145.80, 323.37) 314.32 (162.85, 314.32) 0.622
CRP/(mg/L) 7.98 (3.51, 10.85) 18.20 (7.26, 29.32) 0.053
ESR/(mm/h) 50.48±29.64 31.14±14.57 0.003
IgG/(g/L) 14.59±4.78 11.62±3.68 0.004
IgA/(g/L) 2.57±1.20 2.02±1.22 0.002
IgM/(g/L) 2.85±2.36 1.79±1.06 0.005

表4

抗EJ抗体阳性ASS-ILD胸部CT类型"

Group Overall (n=57) Ruccrence (n=21) Non-ruccrence (n=25)
NISP 40 (70.18) 16 (76.19) 19 (76.00)
OP 4 (7.02) 1 (4.76) 1 (4.00)
UIP 6 (10.53) 2 (9.52) 3 (12.00)
NSIP+OP 2 (3.51) 0 (0.00) 1 (4.00)
NSIP+UIP 4 (7.02) 2 (9.52) 1 (4.00)
LIP 1 (1.75) 0 (0.00) 1 (4.00)

表5

ILD复发多因素二元Logistics分析"

Items β s t P OR OR(95%CI)
ESR 0.023 0.013 2.850 0.091 1.023 0.996, 1.050
IgM 0.203 0.293 0.482 0.488 1.226 0.690, 2.176
CD8+ T 0.065 0.036 3.273 0.070 1.067 0.995, 1.144
1 Aggarwal R , Cassidy E , Fertig N , et al. Patients with non-Jo-1 anti-tRNA synthetase autoantibodies have worse survival than Jo-1 positive patients[J]. Ann Rheum Dis, 2014, 73 (1): 227- 232.
doi: 10.1136/annrheumdis-2012-201800
2 Sreevilasan SK , Devarasetti P , Narahari NK , et al. Clinical profile and treatment outcomes in antisynthetase syndrome: A tertiary centre experience[J]. Rheumatol Adv Pract, 2021, 5 (Suppl 2): ii10- ii18.
3 Hamaguchi Y , Fujimoto M , Matsushita T , et al. Common and distinct clinical features in adult patients with anti-aminoacyl-tRNA synthetase antibodies: Heterogeneity within the syndrome[J]. PLoS One, 2013, 8 (4): e60442.
doi: 10.1371/journal.pone.0060442
4 Teel A , Lu J , Park J , et al. The role of myositis-specific autoantibodies and the management of interstitial lung disease in idiopathic inflammatory myopathies: A systematic review[J]. Semin Arthritis Rheum, 2022, 57, 152088.
doi: 10.1016/j.semarthrit.2022.152088
5 Zhang Y , Ge Y , Yang H , et al. Clinical features and outcomes of the patients with anti-glycyl tRNA synthetase syndrome[J]. Clin Rheumatol, 2020, 39 (8): 2417- 2424.
doi: 10.1007/s10067-020-04979-8
6 Watanabe K , Handa T , Tanizawa K , et al. Detection of antisynthetase syndrome in patients with idiopathic interstitial pneumonias[J]. Respir Med, 2011, 105 (8): 1238- 1247.
doi: 10.1016/j.rmed.2011.03.022
7 Sasano H , Hagiwara E , Kitamura H , et al. Long-term clinical course of anti-glycyl tRNA synthetase (anti-EJ) antibody-related interstitial lung disease pathologically proven by surgical lung biopsy[J]. BMC Pulm Med, 2016, 16 (1): 168.
doi: 10.1186/s12890-016-0325-y
8 Hozumi H , Fujisawa T , Nakashima R , et al. Efficacy of glucocorticoids and calcineurin inhibitors for anti-aminoacyl-trna synthetase antibody-positive polymyositis/dermatomyositis-associated interstitial lung disease: A propensity score-matched analysis[J]. J Rheumatol, 2019, 46 (5): 509- 517.
doi: 10.3899/jrheum.180778
9 Yorishima Y , Tominaga M , Fujimoto K , et al. Combination of prednisolone and calcineurin inhibitors prevents lung function decline in patients with anti-aminoacyl-tRNA synthetase antibody-positive polymyositis/dermatomyositis[J]. Kurume Med J, 2023, 69 (1/2): 19- 30.
10 Martínez-García EA , Lujano-Benítez AV , Gercía-De La Torre Ⅰ , et al. Good response to mycophenolate mofetil on treatment of interstitial lung disease in polymyositis associated with antisynthetase syndrome positive for anti-EJ and anti-Ro52 antibodies[J]. Clin Rheumatol, 2020, 39 (9): 2837- 2839.
doi: 10.1007/s10067-020-05075-7
11 Langlois V , Gillibert A , Uzunhan Y , et al. Rituximab and cyclophosphamide in antisynthetase syndrome-related interstitial lung disease: An observational retrospective study[J]. J Rheumatol, 2020, 47 (11): 1678- 1686.
doi: 10.3899/jrheum.190505
12 Liu Y , Liu X , Xie M , et al. Clinical characteristics of patients with anti-EJ antisynthetase syndrome associated interstitial lung disease and literature review[J]. Respir Med, 2020, 165, 105920.
doi: 10.1016/j.rmed.2020.105920
13 Connors GR , Christopher-Stine L , Oddis CV , et al. Interstitial lung disease associated with the idiopathic inflammatory myopathies: What progress has been made in thepast 35 years[J]. Chest, 2010, 138 (6): 1464- 1474.
doi: 10.1378/chest.10-0180
14 Bohan A , Peter JB . Polymyositis and dermatomyositis (first of two parts)[J]. N Engl J Med, 1975, 292 (7): 344- 347.
doi: 10.1056/NEJM197502132920706
15 Raghu G , Remy-Jardin M , Richeldi L , et al. Idiopathic pulmonary fibrosis (an update) and progressive pulmonary fibrosis in adults: An official ATS/ERS/JRS /ALAT clinical practice guideline[J]. Am J Respir Crit Care Med, 2022, 205 (9): e18- e47.
doi: 10.1164/rccm.202202-0399ST
16 Targoff IN . Autoantibodies to aminoacyl-transfer RNA synthetases for isoleucine and glycine. Two additional synthetases are antigenic in myositis[J]. J Immunol, 1990, 144 (5): 1737- 1743.
doi: 10.4049/jimmunol.144.5.1737
17 Tang HS, Tang IYK, Ho RTC, et al. Clinical heterogeneity and prognostic factors of anti-synthetase syndrome: A multi-centered retrospective cohort study[J]. Rheumatology (Oxford), 2023 (2023-12-14)[2024-09-01]. https://Doi.org/10.1093/rheumatology/kead671.
18 García-Bravo L , Calle-Rubio M , Fernández-Arquero M , et al. Association of anti-SARS-COV-2 vaccine with increased incidence of myositis-related anti-RNA-synthetases auto-antibodies[J]. J Transl Autoimmun, 2022, 5, 100160.
doi: 10.1016/j.jtauto.2022.100160
19 Irie Y , Wakabayashi H , Matuzawa Y , et al. A case of anti-synthetase syndrome with anti-glycyl tRNA synthetases antibody de-veloped after COVID-19[J]. Cureus, 2024, 16 (4): e58004.
20 Shimizu H , Matsumoto H , Sasajima T , et al. New-onset dermatomyositis following COVID-19: A case report[J]. Front Immunol, 2022, 13, 1002329.
doi: 10.3389/fimmu.2022.1002329
21 Peña C , Kalara N , Velagapudi P . A case of antisynthetase syndrome in the setting of SARS-Cov-2 infection[J]. Cureus, 2023, 15 (6): e40588.
22 Elsayed M , Abdelgabar A , Karmani J , et al. A case of antisynthetase syndrome initially presented with interstitial lung disease mimicking COVID-19[J]. J Med Cases, 2023, 14 (1): 25- 30.
doi: 10.14740/jmc4031
23 Tranah E , MacBrayne A , Bhadauria N , et al. A case of antisynthetase syndrome presenting solely with life-threatening interstitial lung disease[J]. Clin Med (Lond), 2023, 23 (1): 85- 87.
24 周云, 吕成银, 尤含笑, 等. 不同抗体亚型抗合成酶综合征并发间质性肺疾病临床特征分析[J]. 中华风湿病学杂志, 2024, 28 (8): 538- 544.
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ISSN 1671-167X
CN 11-4691/R
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