合并抗TRIM21/Ro52抗体阳性的抗SRP阳性坏死性肌病患者临床特点分析

doi:10.16150/j.1671-2870.2023.03.07

摘要/Abstract

摘要：

目的：探讨合并抗TRIM21/Ro52抗体的抗信号识别颗粒（signal recognition particle, SRP）抗体阳性免疫介导的坏死性肌病（immune-mediated necrotizing myopathy，IMNM）患者的临床特征。方法：回顾收集2010年至2021年华中科技大学同济医学院附属同济医院收治的抗SRP抗体阳性IMNM患者（57例）的临床资料。将患者按血清肌炎相关性抗体（myositis-associated autoantibody, MAA）抗TRIM21/Ro52抗体分为抗TRIM21/Ro52抗体阳性组（以下简称抗体阳性组）和抗TRIM21/Ro52抗体阴性组（以下简称抗体阴性组），对2组患者的临床特点、实验室检查、转归预后进行对比分析。结果：本研究抗TRIM21/Ro52抗体阳性（抗体阳性组）患者为23例，抗体阴性患者（抗体阴性组）为34例。抗体阳性组的间质性肺病（interstitial lung disease, ILD）发生比例高于抗体阴性组（21.7%比2.9%，P=0.034），抗体阳性组的抗核抗体（antinuclear antibodies，ANA）高滴度表达（滴度≥1∶1000）比例（69.5%比 32.3%，P=0.008）、血清中性粒细胞计数（8.18 × 10⁹/L比3.93 × 10⁹/L; P=0.034）和白细胞计数(11.685×10⁹/L比6.98×10⁹/L，P=0.044)显著高于抗体阴性组，且上述4项指标均与抗TRIM21/Ro52抗体表达具有一定正相关（r值分别为0.312、0.351、0.290、0.274，P值分别为0.019、0.008、0.035、0.043）。57例抗SRP (+) IMNM患者在接受了83（62~96）个月的随访，51例（89.4%）患者接受了糖皮质激素治疗（或）联合免疫抑制剂治疗，其中22例（95.6%，22/23）抗TRIM21/Ro52抗体阳性患者接受免疫治疗后病情得到好转，1例（4.3%，1/23）患者失访；29例（85.3%，29/34）抗TRIM21/Ro52抗体阴性而接受免疫治疗的患者中，24例（70.6%，24/34）患者病情得到好转，其余5例（14.7%，5/34）患者临床症状未得到显著改善，1例（2.9%）患者失访。结论：抗TRIM21/Ro52抗体阳性的抗SRP抗体阳性IMNM患者更易合并ILD，血清炎性指标水平显著升高，更容易出现高滴度ANA表达。抗TRIM21/Ro52抗体IMNM患者对激素联合免疫抑制剂治疗反应良好。

关键词: 坏死性肌病, 抗SRP抗体, 抗TRIM21/Ro52抗体, 临床特点, 预后

Abstract:

Objective: To explore the clinical characteristics of anti-SRP antibody positive immune-mediated necrotizing myopathy (IMNM) with anti-TRIM21/Ro52 antibody positive. Methods: The data of 57 patients with anti-SRP antibody positive (+) IMNM admitted to the Neurology Department at Tongji Hospital between 2010 and 2021 were retrospectively analyzed. Patients were divided into anti-TRIM21/Ro52 antibody-positive group (positive group) and anti-TRIM21/Ro52 antibody-negative group (negative group) according to serum myositis-associated autoantibody (MAA) anti-TRIM21/Ro52 antibody. The clinical characteristics, laboratory test results, outcomes and prognosis of the two groups were compared and analyzed. Results: Patients with anti-SRP antibody(+) IMNM were enrolled, including anti-TRIM21/Ro52 positive patients (n=23, positive group) and anti-TRIM21/Ro52 negative patients (n=34, negative group). Higher prevalence of interstitial lung disease (ILD) (21.7% vs 2.9%; P=0.034) and high titer antinuclear antibodies (69.5% vs 32.3%; P=0.008) were observed in positive group than those in negative group, as well as the serum neutrophil counts（8.18×10⁹/L vs 3.93×10⁹/L, P=0.034）and white blood cell counts（11.685×10⁹/L vs 6.98×10⁹/L, P=0.044）. All above indicators were positively correlated with the expression of anti-TRIM21/Ro52 antibody（r=0.312, 0.351, 0.290, 0.274, P=0.019, 0.008, 0.035, 0.043）. Fifty-seven patients of anti-SRP antibody (+) IMNM were followed up for 83 (62-96) months. Fifty-one (89.4%) patients received glucocorticoid therapy (or) combination with immunotherapy, and 22 (95.6%) patients in positive group achieved remission, and one patient (4.3%) was lost to follow-up. Among 29 (85.3%) patients of negative group who received immunotherapy, 24 patients (70.6%) were improved, while the remaining 5 patients (14.7%) were not improved, 1 patient (2.9%) was lost to follow-up. Conclusions: Anti-SRP (+) IMNM patients with anti-TRIM21/Ro52 antibody are more likely to be complicated with ILD and have higher inflammatory indicators and ANA titer levels. IMNM patients with anti-TRIM21/Ro52 antibody positive respond well to corticosteroids and immunosuppressive therapy.

Key words: Immune-mediated necrotizing myopathy, Anti-SRP antibody, Anti-TRIM21/Ro52 antibody, Clinical characteristics, Prognosis

中图分类号:

R593.2

徐莉, 高华杰, 杨梦歌, 李悦, 季苏琼. 合并抗TRIM21/Ro52抗体阳性的抗SRP阳性坏死性肌病患者临床特点分析[J]. 诊断学理论与实践, 2023, 22(03): 247-254.

XU Li, GAO Huajie, YANG Mengge, LI Yue, JI Suqiong. Clinical characteristics of anti-SRP antibody positive immune-mediated necrotizing myopathy with anti-TRIM21/Ro52 antibody positive[J]. Journal of Diagnostics Concepts & Practice, 2023, 22(03): 247-254.

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Items	anti-TRIM21/Ro52 positive group (n=23)	anti-TRIM21/Ro52 negative group (n=34)	P value
Sex
Male	10（43.5%）	10（29.4%）	0.718
Female	13（56.5%）	24（70.6%）	0.718
Age at myositis diagnosis (years)	44.9±10.1	44.3±18.4	0.868
Disease duration (months)	6	5.5	0.345
Clinical manifestation
Upper promixal limbs weakness (≤3,MRC)	7（30%)	16（47%)	0.275
Upper distal limbs weakness (≤3,MRC)	2（9%）	10（29%）	0.097
Lower promixal limbs weakness(≤3,MRC)	8（35%)	19（56%）	0.177
Lower distal limbs weakness (≤3,MRC)	7（30%）	11（32%）	>0.999
Atrophy	10（43.5%）	9（26.4%）	0.253
Dyspnea	1（4.3%）	2（5.9%）	>0.999
Dysphagia	5（21.7%）	7（20.6%）	>0.999
Myalgia	12（52.1%）	15（44.1%）	0.597
Rash	2（8.7%）	2（5.9%）	>0.999
Thyroid dysfunction	10（43.5%）	15（44.1%）	0.563
Tumor marker abnormality	8（34.8%）	13（38.2%）	0.752
Laboratory examinations
CK (U/L)	2629	1795	0.49
LDH (U/L)	541	534	0.79
ALT (U/L)	97	83	0.626
AST (U/L)	83	88	0.771
Cr (umol/L)	35	43±15	0.141
Myoglobin (ng/mL)	605±460	284±307	0.071
CK-MB (ng/mL)	98±90	54.4	0.877
cTnI (pg/mL)	31±41	28.4	0.339
WBC (×10⁹/L)	11.685	6.98	0.044
Neutro (×10⁹/L)	8.18	3.93	0.034
Lym (×10⁹/L)	2.18	2.11	0.864
ASS antibody	3 (13%)	2 (5.9%)	0.384
ANA (titer 1∶1000)	6 (42.9%)	4 (26.7%)	0.008
ANA (titer 1∶3200)	4 (28.6%)	5 (33.3%)	0.008
ILD	5 (21.7%)	1 (2.9%)	0.034
Cardiac dysfunction	5 (21.7%)	10（29.4%）	0.542
Treatment
Symptomatic treatment	1 (4.3%)	5（14.7%）
Glucocorticoid monotherapy	10（43.5%）	14（41.2%）
Glucocorticoid and Immunosuppressant	12（52.2%）	15（44.1%）
Outcome
Basically normal	4 (17.4%)	4 (11.8%)	0.076
Marked improvement	18 (78.3%)	24（70.6%）
No improvement	0	5（14.7%）
Relapse	1(4.3%)	1（2.9%）

Indice	Anti-Ro52 antibody	High titer ANA
Anti-Ro52 antibody	-	0.351 (0.008)
Creatine kinase	0.098 (0.487)	0.381 (0.005)
WBC count	0.274 (0.043)	0.018 (0.894)
Neutro count	0.29 (0.035)	-0.027 (0.847)
High titer ANA	0.351 (0.008)	-
ILD	0.312 (0.019)	0.141 (0.301)