Rheumatic disease spectrum and immunological profile of anti-PM/Scl antibodies in idiopathic inflammatory myopathies

Yirui LIAN; Jingxuan LIU; Liang ZHAO; Jing ZHAO; Sitian ZANG; Yuhui LI

doi:10.19723/j.issn.1671-167X.2025.06.002

Journal of Peking University(Health Sciences) >

2025 , Vol. 57 >Issue 6: 1018 - 1023

DOI: https://doi.org/10.19723/j.issn.1671-167X.2025.06.002

Rheumatic disease spectrum and immunological profile of anti-PM/Scl antibodies in idiopathic inflammatory myopathies

Yirui LIAN ¹ ,
Jingxuan LIU ² ,
Liang ZHAO ¹ ,
Jing ZHAO ¹ ,
Sitian ZANG ¹ ,
Yuhui LI ^,¹^,²^,*

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1. Department of Rheumatology and Immunology, Peking University People' s Hospital, Beijing 1000444, China
2. Department of Rheumatology and Immunology, Peking University People' s Hospital Qingdao Hospital, Qingdao 266000, Shandong, China

LI Yuhui, e-mail, liyuhui84@163.com

Received date: 2025-08-30

Online published: 2025-10-21

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Abstract

Objective: To systematically investigate the rheumatic disease spectrum associated with anti-PM/Scl antibodies and to clarify their clinical significance in idiopathic inflammatory myopathies (IIM). Methods: Patients who were tested positive for anti-PM/Scl antibodies by immunoblotting at Peking University People' s Hospital from January 2016 to December 2024 were enrolled. Clinical and immunolo gical data were systematically collected and compared across the subgroups defined by anti-PM/Scl75, anti-PM/Scl100, or dual antibody positivity. Results: A total of 422 anti-PM/Scl-positive patients were enrolled. Among them, 83.2% (351/422) were diagnosed with connective tissue disease (CTD), 7.8% (33/422) were not diagnosed with CTD, and 9.0% (38/422) had an undetermined clinical diagnosis. Among 422 patients, most commonly represented by IIM (19.7%), systemic sclerosis (SSc, 14.2%), overlap syndrome (11.8%), undifferentiated CTD (UCTD, 10.4%), rheumatoid arthritis (6.9%), Sjögren syndrome (6.4%), and systemic lupus erythematosus (6.2%), the remaining diseases accounting for 24.4%. Within the IIM subgroup, dermatomyositis predominated (74.7%), followed next by anti-synthetase syndrome (21.7%) and immune-mediated necrotizing myopathy (3.6%). Anti-PM/Scl75 antibodies were detected in 52.1% (220/422) of the total patients, anti-PM/Scl100 in 43.6% (184/422), and both in 4.3% (18/422). In the subsequent detailed analysis of the anti-PM/ Scl-positive subgroup, double-positive patients showed a significantly higher prevalence of SSc (38.9% vs. 14.1% vs. 12.0%, P=0.015) and interstitial lung disease (ILD, 70.6% vs. 28.8% vs. 35.4%, P=0.002) than those individuals with single antibody positivity alone. Raynaud phenomenon was observed more frequently in both the double-positive and anti-PM/Scl75-positive groups than in the anti-PM/Scl100-positive group (29.4% vs. 21.3% vs. 10.9%, P=0.007). The measured proportion of peri-pheral CD8⁺ T cells was also higher in double-positive patients (35.9%±14.1% vs. 30.4%±11.2% vs. 26.5%±9.7%, P= 0.008), whereas absolute regulatory T-cell levels were lower in the anti-PM/Scl75-positive group compared directly with the anti-PM/Scl100-positive group [7.6% (5.4%, 10.9%) vs. 9.0% (7.9%, 12.0%) vs. 8.8% (5.2%, 9.7%), P=0.017]. Additionally, co-positivity for anti-PM/Scl and other myositis- specific or myositis-associated antibodies was strongly associated with an increased frequency of ILD (P < 0.05). Conclusion: Anti-PM/Scl antibodies define a broad disease spectrum encompassing IIM, SSc, overlap syndromes, and UCTD. Dual positivity for anti-PM/Scl75 and anti-PM/Scl100 identifies patients prone to systemic sclerosis and pulmonary involvement, suggesting additive pathogenic effects of the two antibody specificities.

Key words： Anti-PM/Scl antibody; Idiopathic inflammatory myopathy; Connective tissue disease; CD8⁺ T cells

Cite this article

Yirui LIAN , Jingxuan LIU , Liang ZHAO , Jing ZHAO , Sitian ZANG , Yuhui LI . Rheumatic disease spectrum and immunological profile of anti-PM/Scl antibodies in idiopathic inflammatory myopathies[J]. Journal of Peking University(Health Sciences), 2025 , 57(6) : 1018 -1023 . DOI: 10.19723/j.issn.1671-167X.2025.06.002

抗PM/Scl抗体所对应的抗原主要是PM/Scl复合物的核仁蛋白复合体中的不同组分，该复合物参与RNA加工及降解，与核糖体RNA前体成熟密切相关，其抗原蛋白相对分子质量分别为75 000 (抗PM/Scl75抗体) 和100 000 (抗PM/Scl100抗体)^[1-2]。目前已知抗PM/Scl抗体不仅存在于特发性炎性肌病(idiopathic inflammatory myopathies，IIM)、系统性硬化症(systemic sclerosis，SSc) 中，其他疾病如类风湿关节炎、系统性红斑狼疮、干燥综合征等也可检测到该抗体^[3-5]。抗PM/Scl抗体阳性SSc患者临床表现主要为肌肉受累和肺部受累，后者常表现为间质性肺病(interstitial lung disease，ILD) ^[6-7]，但抗PM/Scl抗体在IIM及其他疾病中的作用并不完全清楚。IIM的发病机制错综复杂，受到环境和遗传因素相互作用的影响，其中，致病性自身抗体破坏特定自身抗原是主要原因之一^[8-10]。抗PM/Scl抗体在IIM中有一定的诊断价值，但相关抗体亚型缺乏系统性分析。本研究旨在通过大样本真实世界研究，分析抗PM/Scl抗体阳性患者的临床表现和实验室检查数据，探究抗PM/Scl抗体阳性患者的风湿性疾病谱及其在IIM中的免疫学特点。

1 资料与方法

1.1 一般资料

纳入2016年1月至2024年12月于北京大学人民医院检测出抗PM/Scl抗体阳性的所有患者，记录其人口学及临床资料，包括性别、起病年龄、临床表现、免疫学指标等。IIM的诊断依据2017年美国风湿病学会/欧洲抗风湿病学联盟(American College of Rheumatology/ European League Against Rheumatism, ACR/EULAR) 分类标准^[11]；SSc的诊断依据2013年ACR/EULAR分类标准^[12]。免疫学检测包括肌炎相关抗体(myositis associated antibodies, MAAs)和肌炎特异性抗体(myositis specific antibo-dies, MSAs)，检测项目包括抗PM/Scl、Ku、Ro52、U1RNP、Mi-2、MDA5、TIF1γ、NXP2、SAE、EJ、OJ、Jo-1、PL7、PL12、SRP和HMGCR抗体^[3]。

1.2 检测方法

抗PM-Scl抗体及MSAs、MAAs采用免疫印迹法检测，所用试剂盒由德国欧蒙公司提供(货号：DL 1530-1601-4 G)，结果判读通过EUROLineScan软件完成。判定标准如下：检测值＜6为阴性，6~10为临界范围(本研究中归为阴性)，≥11为阳性。

1.3 统计学分析

采用SPSS 27.0软件进行统计学分析。对3组间数据进行比较时，符合正态分布的计量资料用均数±标准差表示，采用单因素方差分析(One-Way ANOVA)；若ANOVA结果显示组间差异有统计学意义(P＜0.05)，进一步Bonferroni校正进行两两比较。不符合正态分布的计量资料用中位数(P₂₅，P₇₅) 表示，采用Kruskal-Wallis检验，若结果显示组间差异显著，进一步采用Dunn检验(Bonferroni校正) 进行两两比较。针对两组间数据，符合正态分布的计量资料用独立样本t检验，不符合正态分布的计量资料用Mann-Whitney U检验。分类变量用例数(%) 表示，使用卡方检验及Fisher精确概率进行分析，P＜0.05为差异有统计学意义。

2 结果

2.1 抗PM/Scl抗体阳性患者的疾病谱特点

共纳入抗PM/Scl抗体阳性患者422例，其中女性335例，男性87例，男女比例约为1 ∶ 3.9；平均年龄(50.7±16.2)岁。422例患者中结缔组织病(connective tissue disease, CTD)者共351例(83.2%)，未诊断为CTD者33例(7.8%)，未明确临床诊断者38例(9.0%)。CTD 351例患者中，IIM 83例(19.7%)，包括皮肌炎(dermatomyositis，DM) 62例(14.7%)、抗合成酶综合征(anti-syntheta se syndrome，ASyS) 18例(4.3%)、免疫介导坏死性肌病(immune-mediated necrotizing myopathy，IMNM) 3例(0.7%)；SSc 60例(14.2%)；重叠综合征50例(11.8%)；未分化结缔组织病(undifferentiated connective tissue disease, UCTD) 44例(10.4%)；类风湿关节炎(rheumatoid arthritis, RA) 29例(6.9%)；干燥综合征27例(6.4%)；系统性红斑狼疮26例(6.2%)；伴自身免疫特征的间质性肺病13例(3.1%)；系统性血管炎8例(1.9%)；混合性结缔组织病5例(1.2%)；风湿性多肌痛4例(0.9%)；抗磷脂综合征2例(0.5%)。未诊断CTD的33例患者包括痛风5例(1.2%)、成人Still病3例(0.7%)、骨关节炎3例(0.7%)、药物性皮炎3例(0.7%)、淋巴瘤3例(0.7%)、感染性疾病3例(0.7%，支原体感染2例、衣原体感染1例)、免疫性血小板减少性紫癜3例(0.7%)及荨麻疹、周围神经病、阵发性睡眠性血红蛋白尿、骨髓增生异常综合征、脂肪肝各2例。

2.2 抗PM/Scl抗体阳性亚组临床特征及实验室检查比较

纳入的抗PM/Scl抗体阳性422例患者中，220例(52.1%) 患者抗PM/Scl75抗体阳性，184例(43.6%) 患者抗PM/Scl100抗体阳性，双阳性患者为18例(4.3%)。抗PM/Scl抗体阳性亚组分析比较发现，抗体双阳性患者较单一抗PM/Scl75或抗PM/Scl100发生SSc (38.9% vs. 14.1% vs. 12.0%，P=0.015) 和间质性肺病(70.6% vs. 28.8% vs. 35.4%，P=0.002) 的比例均更高；抗PM/Scl100抗体阳性者发生雷诺(Raynaud)现象的风险低于抗PM/Scl75抗体阳性者及抗体双阳性者(10.9% vs. 21.3% vs. 29.4%, P=0.007，表 1)。

表1 抗PM/Scl抗体阳性亚组临床特征及实验室检查比较

Table 1 Clinical and immunological characteristics of anti-PM/Scl antibody subgroups

Variables	Anti-PM/Scl75 (+), n(%)	Anti-PM/Scl100 (+), n(%)	Anti-PM/Scl75/100 (+), n(%)	P value
Female	181 (82.3)	138 (75.0)	16 (88.9)	0.134^c
DM	29 (13.2)	27 (14.7)	6 (33.3)	0.077^c
IMNM	3 (1.4)	0 (0)	0 (0)	0.346^c
ASyS	8 (3.6)	10 (5.4)	0 (0)	0.560^c
SSc	31 (14.1)^a	22 (12.0)^a	7 (38.9)^b	0.015^c
Gottron sign	27/212 (12.7)	25/174 (14.4)	5/17 (29.4)	0.159^c
Heliotrope rash	17/211 (8.1)	19/174 (10.9)	0 (0)	0.377^c
Mechanic’s hands	25/211 (11.8)^a	17/174 (9.8)^a	6/17 (35.3)^b	0.018^c
Muscle weakness	38/211 (18.0)	30/174 (17.2)	5/17 (29.4)	0.425^c
Myalgia	49/209 (23.4)	42/171 (24.6)	5/17 (29.4)	0.787^c
Raynaud phenomenon	45/211 (21.3)^b	19/174 (10.9)^a	5/17 (29.4)^b	0.007^c
ILD	61/212 (28.8)^a	62/175 (35.4)^a	12/17 (70.6)^b	0.002^c
Arthritis	98/211 (46.4)	88/173 (50.9)	10/17 (58.8)	0.487
Elevated CK	41/200 (20.5)	29/154 (18.8)	1/16 (6.3)	0.461^c
ANA(+)	135/202 (66.8)	107/174 (61.5)	11/16 (68.8)	0.539
Anti-Jo-1(+)	10 (4.5)	6 (3.3)	0 (0)	0.810^c
Anti-PL7(+)	7 (3.2)	2 (1.1)	0 (0)	0.382^c
Anti-PL12(+)	6 (2.7)	6 (3.3)	0 (0)	0.869^c
Anti-Mi-2(+)	8 (3.6)	9 (4.9)	1 (5.6)	0.620^c
Anti-MDA5(+)	5 (2.3)	1 (0.5)	0 (0)	0.405^c
Anti-TIF1γ(+)	1 (0.5)	2 (1.1)	0 (0)	0.644^c
Anti-NXP2(+)	2 (0.9)	1 (0.5)	0 (0)	>0.999^c
Anti-SAE(+)	1 (0.5)	0 (0)	0 (0)	>0.999^c
Anti-SRP(+)	6 (2.7)	3 (1.6)	0 (0)	0.676^c
Anti-HMGCR(+)	1 (0.5)	0 (0)	0 (0)	>0.999^c
Anti-Scl70(+)	9 (4.1)	3 (1.6)	0 (0)	0.344^c
Anti-U1RNP(+)	12 (5.5)	5 (2.7)	0 (0)	0.337^c
Anti-Ro52(+)	39/194 (20.1)	20/161 (12.4)	2/14 (14.3)	0.147^c

a, b, indicate results of post-hoc comparisons, identical letters indicate no significant difference between groups, while different letters indicate a statistically significant difference; c, analyzed by Fisher ’ s exact test. Anti-PM/Scl, anti-polymyositis-scleroderma; DM, dermatomyositis; IMNM, immune-mediated necrotizing myopathy; ASyS, anti-synthetase syndrome; SSc, systemic sclerosis；ILD, interstitial lung disease; CK, creatine kinase; ANA, antinuclear antibodies; Jo-1, histidyl tRNA synthetase; PL7, threonyl-tRNA synthetase; PL12, alanyl-tRNA synthetase; Mi-2，component of the nucleosome remodeling-deacetylase complex; MDA5, melanoma differentiation associated gene 5; TIF1γ, transcriptional intermediary factor 1γ; NXP2, nuclear matrix protein 2; SAE, small ubiquitin like modifier activating enzyme; SRP, signal recognition particle; HMGCR, 3-hydroxy -3-methylglutaryl-CoA reductase; Scl70, topoisomerase Ⅰ; U1RNP, ribonucleoprotein; Ro52, tripartite motif-containing protein 21.

2.3 抗PM/Scl抗体阳性亚组外周血细胞免疫学特征比较

在抗PM/Scl抗体阳性患者中，不同抗体亚组外周血淋巴细胞亚群分布存在差异。抗PM/Scl100抗体阳性者的总T细胞比例低于抗PM/Scl75抗体阳性者，而抗体双阳性患者与两组单一抗体阳性患者间的总T细胞比例差异无统计学意义[68.9% (60.1%，74.5%) vs. 73.3% (66.2%，82.0%) vs. 78.9% (68.4%，84.2%)，P=0.001]。抗体双阳患者与抗PM/Scl75抗体阳性者的CD8⁺T细胞比例均高于抗PM/Scl100抗体阳性者(35.9%±14.1% vs. 30.4%±11.2% vs. 26.5%±9.7%, P=0.008)。抗PM/Scl75抗体阳性者调节性T细胞(regulatory T cell，Treg) 水平低于抗PM/Scl100抗体阳性者，而抗体双阳性患者与两组单一抗体阳性患者间的调节性T细胞差异无统计学意义[7.6% (5.4%, 10.9%) vs. 9.0% (7.9%, 12.0%) vs. 8.8% (5.2%, 9.7%), P=0.017，(表 2)]。

表2 抗PM/Scl抗体阳性亚组免疫学特征比较

Table 2 Comparison of immunological characteristics of anti-PM/Scl antibody subgroups

Variables	Anti-PM/Scl 75(+) (n=220)	Anti-PM/Scl 100(+) (n=184)	Anti-PM/Scl 75/100(+) (n=18)	P value
Lymphocyte T/μL	1 064.0 (743.0, 1 389.0)	1 070.0 (694.0, 1 350.5)	808.0 (730.5, 1 762.3)	0.885
CD3⁺total T/%	73.3 (66.2, 82.0)^b	68.9 (60.1, 74.5)^a	78.9 (68.4, 84.2)^{a, b}	0.001
CD4⁺ helper T/μL	556.0 (357.0, 759.0)	528.0 (374.3, 824.5)	445.0 (295.0, 946.7)	0.899
CD4⁺helper T/%	40.0±11.6	37.6±10.0	39.2±11.9	0.346
CD8⁺cytotoxic T /μL	404.8 (235.5, 571.3)	360.7 (195.0, 525.4)	490.0 (289.0, 743.6)	0.396
CD8⁺cytotoxic T/%	30.4±11.2^b	26.5±9.7^a	35.9±14.1^b	0.008
CD19⁺B /μL	162.0 (74.0, 300.0)	196.4 (94.2，363.0)	149.0 (93.4，230.5)	0.378
CD19⁺B /%	11.5 (6.3, 15.6)	13.6 (8.1, 22.6)	11.0 (5.4, 15.8)	0.123
CD56⁺CD16⁺NK /μL	117.0 (65.0, 266.0)	197.0 (87.5, 297.0)	138.0 (84.9, 224.5)	0.099
CD56⁺CD16⁺NK/%	10.2 (4.6, 15.3)	13.0 (7.9, 19.1)	11.4 (4.8, 16.1)	0.062
pTfh/%	2.1 (1.4，3.1)	3.1 (1.7，4.0)	2.0 (1.0，3.1)	0.078
Treg/%	7.6 (5.4, 10.9)^a	9.0 (7.9, 12.0)^b	8.8 (5.2, 9.7)^{a, b}	0.017

Data are presented as $\bar x \pm s$ or M (P₂₅, P₇₅). a, b, indicate results of post-hoc comparisons: identical letters indicate no significant difference between groups, while different letters indicate a statistically significant difference. pTfh, peripheral T follicular helper cells (CD4⁺CD45RA^-CXCR5⁺PD1⁺); Treg, regulatory T cells (CD4⁺CD25^hiCD127^low).

2.4 抗PM/Scl抗体合并MAAs/MSAs患者特征

将抗PM/Scl抗体阳性患者分为抗PM/Scl抗体阳性组(348例) 和抗PM/Scl抗体合并MAAs/MSAs阳性组(74例)，比较两组发现，单纯抗PM/Scl抗体阳性组发生技工手(9.9% vs. 21.4%，P=0.009)、Gottron征(10.8% vs. 29.6%，P＜0.001)、V领征(5.5% vs. 21.1%，P＜0.001)、披肩征(4.0% vs. 19.7%，P＜0.001)、皮肤瘙痒(4.3% vs. 15.5%，P=0.001)、肌无力(15.7% vs. 29.6%，P=0.007)、ILD (31.2% vs. 43.7%，P=0.032)的比例显著低于合并MAAs/MSAs阳性组(表 3)。同时发现抗PM/Scl抗体合并抗PL12抗体(31.2% vs. 66.7%, P=0.030) 及抗PM/Scl抗体合并抗Ro52抗体(31.2% vs. 47.5%, P=0.045)与ILD的发生显著相关。

表3 抗PM/Scl抗体阳性与抗PM/Scl合并MAAs/MSAs阳性患者特征

Table 3 Clinical and immunological features of anti-PM/Scl-positive patients with or without additional MAAs/MSAs

Variables	Anti-PM/Scl(+) (n=348)	Anti-PM/Scl with MAAs/MSAs(+) (n=74)	P value
Female	276 (79.3%)	59 (79.7%)	0.539
Age of onset/years	51.1±15.9	48.9±17.5	0.296
Mechanic’s hands	33/332 (9.9%)	15/70 (21.4%)	0.009
Gottron sign	36/332 (10.8%)	21/71 (29.6%)	＜0.001
Shawl sign	13/329 (4.0%)	14/71 (19.7%)	＜0.001^a
V-sign	18/329 (5.5%)	15/71 (21.1%)	＜0.001
Skin ulceration	19/327 (5.8%)	8/71 (11.3%)	0.086^a
Myalgia	73/326 (22.4%)	23/71 (32.4%)	0.054
Muscle weakness	52/331 (15.7%)	21/71 (29.6%)	0.007
Pruritus	14/329 (4.3%)	11/71 (15.5%)	0.001^a
Skin hypercalcemia	4/329 (1.2%)	1/71 (1.4%)	0.626^a
Arthritis	161/331 (48.6%)	35/70 (50.0%)	0.470
Raynaud phenomenon	60/332 (18.1%)	9/70 (12.9%)	0.192
ILD	104/333 (31.2%)	31/71 (43.7%)	0.032
Elevated CK	54/304 (17.8%)	17/66 (25.8%)	0.095
CD3⁺total T/%	70.8±12.2	69.7±14.7	0.647
CD4⁺helper T/%	38.9±10.9	39.4±11.8	0.798
CD8⁺cytotoxic T/%	27.4 (21.7，36.4)	27.4 (18.2，37.4)	0.652
CD19⁺B /%	11.9 (6.8，17.4)	12.1 (9.0，20.5)	0.552
CD56⁺CD16⁺NK/%	11.5 (6.2，16.7)	9.1 (2.9，18.5)	0.181
Treg/%	8.5 (6.8，10.9)	7.2 (5.1，9.4)	0.114
pTfh/%	2.3 (1.5，3.5)	2.0 (1.3, 4.9)	0.663

Data are presented as $\bar x \pm s$ or M (P₂₅, P₇₅). a, analyzed by Fisher ’ s exact test. MAAs, myositis associated antibodies; MSAs, myositis specific antibodies; ILD, interstitial lung disease; CK, creatine kinase; Treg, regulatory T cells (CD4⁺CD25^hiCD127^low); pTfh, peripheral T follicular helper cells (CD4⁺CD45RA^-CXCR5⁺PD1⁺).

3 讨论

本研究结果显示，抗PM/Scl抗体阳性患者疾病谱广泛，以IIM、SSc、重叠综合征、UCTD为主，既往报道^[13]表明该抗体在SSc、IIM以及重叠综合征中常见，而在UCTD中未见相关报道。抗PM/Scl抗体是一种肌炎相关抗体，并非IIM所特有^[14]。据报道, 2%~5%的SSc患者抗PM/Scl抗体阳性，但在伴发肌炎的SSc重叠综合征中检出率更高^[13]。因此，当临床上检测到抗PM/Scl抗体阳性时，应高度警惕合并肌炎和系统性硬化症的可能。本研究同时发现抗PM/Scl抗体的UCTD诊断不在少数，部分抗PM/Scl抗体阳性患者初次就诊时未能满足任何明确CTD诊断标准(占10.4%)，可能处于疾病早期或未分化阶段，由于该抗体与SSc及IIM的高度相关^[15]，因此，对于这类仅有非特异症状但抗体阳性的患者，应密切随访其向SSc或IIM分化可能。

do Amaral Barbosa等^[16]在一项针对IIM患者的研究中发现，抗PM/Scl抗体阳性组肺受累发生率显著高于阴性组，且技工手、雷诺现象等表现更为多见。近期，Zhu等^[2]在中国另一队列的研究中亦发现，抗PM/Scl抗体合并MSA者与更严重的肺部受累相关。值得注意的是，不同抗PM/Scl抗体亚型所对应的临床表型具有明显的异质性。本研究显示，抗PM/Scl抗体双阳性患者较单阳性者更易合并SSc，ILD的发生率亦显著升高。有研究发现，自身抗体的致病作用不仅取决于其对抗原的识别能力，更与其Fc段所介导的下游免疫效应密切相关，在双阳性患者中，由于抗体可同时靶向同一复合物内的两个不同分子，易形成更大、结构更稳定且空间构象更复杂的免疫复合物(immune complexes, ICs)。与靶向单一抗原形成的ICs相比，这种复杂ICs具有更强的致病潜能，能更有效地激活补体系统，加剧局部组织的炎症，并直接导致细胞损伤，尤其在血管内皮和肺泡损伤中作用显著，最终表现为更严重的临床表型及肌炎与硬皮病重叠表现^[17]。此外，本研究还发现，抗PM/Scl75单阳性患者发生雷诺现象的风险高于抗PM/Scl100单阳性者，提示抗PM/Scl75抗体阳性患者可能具有更突出的硬皮病相关特征或血管病变倾向。

不同肌炎自身抗体所导致临床表型差异的免疫学机制近年来逐渐受到重视。抗PM/Scl抗体针对的是细胞核仁中PM/Scl大分子复合物(核糖核酸酶复合体)的组分，其致病机制尚未完全阐明。一种假说认为，抗PM/Scl抗体可能通过形成免疫复合物影响核酸代谢和细胞凋亡，从而在肌肉和结缔组织中诱发异常的炎症和纤维化反应，这可部分解释为何抗PM/Scl抗体阳性患者同时出现肌肉炎症和硬皮病的纤维化表现^[18-19]。此外，本研究发现，不同抗PM/Scl亚组间的T细胞亚群差异有统计学意义，抗PM/Scl100抗体阳性患者外周血中Treg比例显著高于抗PM/Scl75抗体阳性者。Treg是抑制机体过度免疫反应的重要免疫细胞，可通过分泌白细胞介素-10、转化生长因子-β等抑制性细胞因子，或经表面分子CTLA-4直接抑制抗原呈递细胞活化，从而营造抗炎微环境^[20]。Treg比例升高可能反映机体对自身免疫反应的负反馈调节增强，这或可部分解释该组患者临床症状相对轻的原因，后续仍需扩大样本量，进行长期随访及机制学研究，以进一步阐明其免疫学意义。

本研究亦存在一定局限性：(1)为回顾性分析，数据来自单一中心，存在潜在选择偏倚；(2)双阳性亚组的样本量较小，虽然通过敏感性分析验证了主要结论的可靠性，但仍需多中心、更大样本研究进一步证实本研究结果。

综上所述，抗PM/Scl抗体阳性患者疾病谱广，以IIM、SSc、重叠综合征、UCTD为主；抗PM/Scl75抗体阳性比例高，而抗体双阳比例低；抗PM/Scl抗体双阳性患者更易发生SSc、间质性肺病。

利益冲突 所有作者均声明不存在利益冲突。

作者贡献声明 练益瑞：撰写论文初稿，收集、分析数据；刘静璇：撰写论文初稿，收集数据；赵亮：收集、整理数据；赵静：提供数据；臧思田：统计学分析；李玉慧：提供研究思路，指导修改论文。所有作者均参与论文修改，并对最终文稿进行审读和确认。

References

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