抗合成酶综合征合并心脏受累患者的临床及免疫学特征

doi:10.19723/j.issn.1671-167X.2021.06.012

摘要/Abstract

摘要：

目的:探讨抗合成酶综合征 (anti-synthetase syndrome, ASS)患者心脏受累的临床及免疫学特征。方法:回顾性分析2003年4月至2020年11月于北京大学人民医院风湿免疫科住院治疗的96例ASS患者资料,包括人口学资料、临床表现(皮疹、肌肉损害等)、合并症及实验室指标(肌酶、炎性标志物、免疫球蛋白、补体、淋巴细胞亚群、自身抗体等), 依据有无心脏受累进行分组比较。结果:ASS患者心脏受累的发生率为25.0% (24/96),心脏受累的患者主要表现为心肌肌钙蛋白升高(75.0%, 18/24)、心包积液(33.3%, 8/24)、左心室舒张功能减退(33.3%, 8/24)、瓣膜反流(33.3%, 8/24)。心脏受累组患者的发病年龄大于无心脏受累组[(54.58±10.58)岁 vs. (48.47±13.22)岁, P=0.043],关节炎的发生率低(37.5% vs. 61.1%, P=0.044)。心脏受累组患者合并急进性间质性肺炎的发生率高于无心脏受累组(54.2% vs. 30.6%, P=0.037)。实验室指标方面,ASS合并心脏受累组的C反应蛋白[13.55 (8.96, 38.35) mg/L vs. 4.60 (1.37, 17.40) mg/L, P=0.001]和乳酸脱氢酶[408.0 (255.0, 587.0) U/L vs. 259.5 (189.8, 393.8) U/L, P=0.007]水平均明显高于无心脏受累组。此外,心脏受累组出现抗Ro-52抗体阳性的患者比例明显高于无心脏受累组(91.7% vs. 69.4%, P=0.029),而合并危险因素、谷丙转氨酶、谷草转氨酶、肌酸激酶、动态红细胞沉降率、铁蛋白、免疫球蛋白G、补体C3、补体C4及T/B/NK淋巴细胞亚群等方面,两组差异无统计学意义。结论:ASS患者心脏受累常见,以心肌受损为主,合并C反应蛋白和乳酸脱氢酶升高、抗Ro-52抗体阳性的ASS患者应警惕心脏受累。

关键词: 抗合成酶综合征, 心肌炎, 肌炎, 自身抗体

Abstract:

Objective: To investigate the clinical and immunological features of cardiac involvement in patients with anti-synthetase syndrome (ASS). Methods: In the study, 96 patients diagnosed with ASS hospitalized in the Department of Rheumatology and Immunology, Peking University People’s Hospital from April 2003 to November 2020 were included. The patients were divided into two groups according to whether they were accompanied with cardiac involvement. Demographic features, clinical characteristics (Gottron’s sign/papules, muscle damage, etc.), comorbidities, laboratory indices (creatine kinase, inflammatory indicators, immunoglobulin, complement, lymphocyte subset, autoantibodies, etc.) were collected and the differences between the two groups were analyzed statistically. Results: The prevalence of cardiac involvement in the patients with ASS was 25.0% (24/96). The ASS patients complicated with cardiac involvement presented with elevated cardiac troponin I (cTnI, 75.0%, 18/24), pericardial effusion (33.3%, 8/24), reduction of left ventricular function (33.3%, 8/24) and valves regurgitation (33.3%, 8/24). The age of onset of the patients with cardiac involvement was older than that of the patients without cardiac involvement [(54.58±10.58) years vs. (48.47±13.22) years, P=0.043). Arthritis was observed less frequently in the patients with cardiac involvement than those without cardiac involvement (37.5% vs. 61.1%, P=0.044). In addition, rapidly progressive interstitial lung disease (54.2% vs. 30.6%, P=0.037) was observed more frequently in the patients with cardiac involvement than those without cardiac involvement. As compared with the ASS patients without cardiac involvement, C-reactive protein (CRP) [(13.55 (8.96, 38.35) mg/L vs. 4.60 (1.37, 17.40) mg/L, P=0.001], and lactate dehydrogenase (LDH) [408.0 (255.0, 587.0) U/L vs. 259.5 (189.8, 393.8) U/L, P=0.007] were significantly higher in the patients with cardiac involvement. Anti-Ro-52 antibody was detected more commonly in the ASS patients with cardiac involvement compared with the patients without cardiac involvement (91.7% vs. 69.4%, P=0.029). No significant differences were found in the comorbidities, alanine transaminase (ALT), aspartate transaminase (AST), creatine kinase (CK), erythrocyte sedimentation rate (ESR), ferritin (Fer), immunoglobulin G (IgG), complement 3 (C3), complement 4 (C4), lymphocyte subset between the two groups. Conclusion: Cardiac involvement is common in ASS, mainly manifested as myocardial damage. It is necessary to be aware of cardiac complications in patients with elevated CRP, elevated LDH and positive anti-Ro-52 antibody.

Key words: Anti-synthetase syndrome, Myocarditis, Myositis, Autoantibodies

中图分类号:

R593.2

罗澜,邢晓燕,肖云抒,陈珂彦,朱冯赟智,张学武,李玉慧. 抗合成酶综合征合并心脏受累患者的临床及免疫学特征[J]. 北京大学学报（医学版）, 2021, 53(6): 1078-1082.

LUO Lan,XING Xiao-yan,XIAO Yun-shu,CHEN Ke-yan,ZHU Feng-yun-zhi,ZHANG Xue-wu,LI Yu-hui. Clinical and immunological characteristics of patients with anti-synthetase syndrome complicated with cardiac involvement[J]. Journal of Peking University (Health Sciences), 2021, 53(6): 1078-1082.

图/表 3

表1

表2

合并心脏受累的ASS患者的临床表现和实验室特征"

Variables	ASS with cardiac involvement (n=24)	ASS without cardiac involvement (n=72)	P value
Demographics
Female	17 (70.8)	49 (68.1)	0.799
Age at onset/years	54.58±10.58	48.47±13.22	0.043
Duration/month	12.0 (3.5, 34.5)	5.5 (2.0, 15.2)	0.108
Clinical features
Fever	13 (54.2)	31 (43.1)	0.344
Mechanic’s hands	16 (66.7)	38 (52.8)	0.235
Gottron’s sign/papules	22 (91.7)	52 (72.2)	0.050
Heliotrope rash	8 (33.3)	14 (19.4)	0.161
V-neck sign	5 (20.8)	14 (19.4)	>0.999
Shawl sign	3 (12.5)	4 (5.6)	0.497
Myalgia	9 (37.5)	39 (54.2)	0.157
Muscle weakness	14 (58.3)	40 (55.6)	0.812
Raynaud’s phenomenon	2 (8.3)	10 (13.9)	0.722
Arthritis	9 (37.5)	44 (61.1)	0.044
Complications
ILD	24 (100.0)	68 (94.4)	0.569
RP-ILD	13 (54.2)	22 (30.6)	0.037
C-ILD	11 (45.8)	46 (63.9)	0.119
Malignancy	1 (4.2)	5 (6.9)	>0.999
PAH	4 (16.7)	7 (9.7)	0.579
Venous thrombosis	3 (12.5)	3 (4.2)	0.163
Risk factors
BMI^a≥24 kg/m²	14 (60.9)	35 (51.5)	0.434
Cigarette	4 (16.7)	13 (18.1)	>0.999
Hypertension	11 (45.8)	19 (26.4)	0.075
Diabetes	5 (20.8)	14 (19.4)	>0.999
Hyperlipidemia	5 (20.8)	14 (19.4)	>0.999
Laboratory features
ALT/(U/L)	40.0 (18.2, 78.0)	29.0 (18.2, 48.0)	0.383
AST/(U/L)	46.5 (20.0, 95.5)	29.5 (20.0, 45.8)	0.129
CK^b /(U/L)	642 (62, 2 167)	138 (44, 661)	0.057
LDH^b/(U/L)	408.0 (255.0, 587.0)	259.5 (189.8, 393.8)	0.007
ESR/(mm/h)	29.3 (17.0, 52.2)	21.0 (8.0, 39.0)	0.074
CRP^c/(mg/L)	13.55 (8.96, 38.35)	4.60 (1.37, 17.40)	0.001
Ferritin^d/(μg/L)	172.6 (56.1, 692.7)	183.6 (66.5, 331.2)	0.837
IgG^e/(g/L)	16.9 (12.3, 22.9)	14.9 (11.6, 17.1)	0.108
C3^f/(g/L)	0.97±0.26	0.98±0.25	0.819
C4^f/(g/L)	0.21 (0.15, 0.24)	0.21 (0.17, 0.27)	0.329
T cell^g/(cells/μL)	728 (530, 1 078)	976 (559, 1 548)	0.209
CD4⁺T cell^g/(cells/μL)	435 (212, 619)	521 (376, 834)	0.388
CD8⁺T cell^g/(cells/μL)	269 (200, 305)	392 (210, 545)	0.233
NK cell^g/(cells/μL)	145 (86, 389)	154 (76, 391)	0.950
T cell^h/%	67.01±15.31	66.51±13.42	0.888
CD4⁺T cell^h/%	38.18±17.08	38.59±10.88	0.918
CD8⁺T cell^h/%	24.4 (18.8, 32.0)	24.1 (18.4, 33.4)	0.987
NK cell^g/%	12.7 (10.6, 29.4)	12.6 (7.1, 18.0)	0.470
CD4⁺/CD8^+h	1.45 (1.09, 2.43)	1.56 (0.95, 2.49)	0.853

表2

表3

参考文献 15

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Variables	Value, n (%)
Elevated cTnI	18 (75.0)
Elevated BNP	4 (16.7)
UCG
Pericardial effusion	8 (33.3)
PAH	4 (16.7)
Reduction of LV function	8 (33.3)
Valves regurgitation	8 (33.3)
Regional wall motion abnormality	1 (4.2)
ECG
QT interval prolongation	2 (8.3)
Abnormal T waves	2 (8.3)
ST-T segment changes	2 (8.3)

Variables	ASS with cardiac involvement (n=24), n(%)	ASS without cardiac involvement (n=72), n(%)	P value
Anti-Jo-1 positivity	11 (45.8)	42 (58.3)	0.286
Anti-PL-7 positivity	3 (12.5)	13 (18.1)	0.752
Anti-PL-12 positivity	4 (16.7)	10 (13.9)	>0.999
Anti-EJ positivity	6 (25.0)	7 (9.7)	0.121
Anti-OJ positivity	0 (0)	5 (6.9)	0.327
Anti-KS positivity	1 (4.2)	0 (0)	0.250
ANA positivity	21 (87.5)	55 (76.4)	0.246
Anti-Ro-52 positivity	22 (91.7)	50 (69.4)	0.029