抗PM/Scl抗体相关风湿性疾病谱及其在特发性炎性肌病中的免疫学特征

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

摘要/Abstract

摘要：

目的: 探究抗PM/Scl抗体的风湿性疾病谱特征及其在特发性炎性肌病(idiopathic inflammatory myopathies, IIM) 中的意义。方法: 回顾性纳入经免疫印迹法检测血清抗PM/Scl抗体阳性的患者，收集并分析患者的临床特征及免疫学指标，比较不同抗PM/Scl抗体亚型(抗PM/Scl75、抗PM/Scl100及双阳性) 患者的临床与免疫学差异。结果: 在纳入的422例抗PM/Scl抗体阳性患者中，结缔组织病(connective tissue disease, CTD) 占83.2% (351/422)，未诊断为CTD者占7.8% (33/422)，未明确临床诊断者占9.0% (38/422)。在422例患者中，IIM占19.7%(83/422)，其次为系统性硬化症(14.2%，60/422)、重叠综合征(11.8%，50/422)、未分化结缔组织病(10.4%，44/422)、类风湿关节炎(6.9%，29/422)、干燥综合征(6.4%，27/422)、系统性红斑狼疮(6.2%，26/422)，其余占24.4%(103/422)。在抗PM/Scl抗体阳性IIM患者中，皮肌炎占比最高(74.7%，62/83)，其次为抗合成酶综合征(21.7%，18/83)和免疫介导坏死性肌病(3.6%，3/83)。在抗PM/Scl抗体阳性患者中，单一抗PM/Scl75抗体阳性患者占52.1% (220/422)，单一抗PM/Scl100抗体阳性占43.6% (184/422)，抗PM/Scl75/100抗体双阳性患者占4.3% (18/422)。在亚组分析中，抗PM/Scl抗体双阳性患者相比于单一抗PM/Scl75阳性或抗PM/Scl100阳性者更易出现系统性硬化症(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)。抗体双阳性患者及抗PM/Scl75阳性患者较抗PM/Scl100阳性患者更易出现雷诺(Raynaud)现象(29.4% vs. 21.3% vs. 10.9%，P=0.007)，外周血CD8⁺T细胞比例更高(35.9%±14.1% vs. 30.4%±11.2% vs. 26.5%±9.7%，P=0.008)。抗PM/Scl75阳性患者调节性T细胞水平低于抗PM/Scl100阳性患者，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]。抗PM/Scl抗体合并肌炎相关抗体/肌炎特异性抗体时，发生间质性肺病的比例升高(P＜0.05)。结论: 抗PM/Scl抗体阳性患者疾病谱广，以IIM、系统性硬化症、重叠综合征和未分化结缔组织病为主；抗PM/Scl75/100双阳性多见于系统性硬化症及肺部损害者。

关键词: 抗PM/Scl抗体, 特发性炎性肌病, 结缔组织病, CD8⁺T细胞

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

中图分类号:

R593.2

练益瑞, 刘静璇, 赵亮, 赵静, 臧思田, 李玉慧. 抗PM/Scl抗体相关风湿性疾病谱及其在特发性炎性肌病中的免疫学特征[J]. 北京大学学报（医学版）, 2025, 57(6): 1018-1023.

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.

图/表 3

表1

表2

表3

参考文献 20

1	Brouwer R , Vree Egberts WTM , Hengstman GJD , et al. Autoantibodies directed to novel components of the PM/Scl complex, the human exosome[J]. Arthritis Res, 2002, 4(2): 134- 138.
2	Zhu L , Zong C , Chen Y , et al. Clinical characteristics of idiopathic inflammatory myopathies patients with anti-PM/Scl antibo-dies[J]. Semin Arthritis Rheum, 2024, 68, 152536. doi: 10.1016/j.semarthrit.2024.152536
3	Liu Y , Zheng Y , Hao H , et al. Narrative review of autoantibodies in idiopathic inflammatory myopathies[J]. Ann Transl Med, 2023, 11(7): 291. doi: 10.21037/atm-21-475
4	Muro Y , Hosono Y , Sugiura K , et al. Anti-PM/Scl antibodies are found in Japanese patients with various systemic autoimmune conditions besides myositis and scleroderma[J]. Arthritis Res Ther, 2015, 17(1): 57. doi: 10.1186/s13075-015-0573-x
5	McHugh NJ , Tansley SL . Autoantibodies in myositis[J]. Nat Rev Rheumatol, 2018, 14(5): 290- 302. doi: 10.1038/nrrheum.2018.56
6	Cavazzana I , Vojinovic T , Airo' P , et al. Systemic sclerosis-specific antibodies: Novel and classical biomarkers[J]. Clin Rev Allergy Immunol, 2023, 64(3): 412- 430.
7	Wodkowski M , Hudson M , Proudman S , et al. Clinical correlates of monospecific anti-PM75 and anti-PM100 antibodies in a tri-nation cohort of 1 574 systemic sclerosis subjects[J]. Autoimmunity, 2015, 48(8): 542- 551. doi: 10.3109/08916934.2015.1077231
8	Musai J , Mammen AL , Pinal-Fernandez I . Recent updates on the pathogenesis of inflammatory myopathies[J]. Curr Rheumatol Rep, 2024, 26(12): 421- 430. doi: 10.1007/s11926-024-01164-7
9	Ogawa-Momohara M , Muro Y . Myositis-specific and myositis-associated autoantibodies: Their clinical characteristics and potential pathogenic roles[J]. Immunol Med, 2025, 48(2): 104- 116. doi: 10.1080/25785826.2024.2413604
10	Damoiseaux J , Vulsteke JB , Tseng CW , et al. Autoantibodies in idiopathic inflammatory myopathies: Clinical associations and laboratory evaluation by mono- and multispecific immunoassays[J]. Autoimmun Rev, 2019, 18(3): 293- 305. doi: 10.1016/j.autrev.2018.10.004
11	Parker MJS , Oldroyd A , Roberts ME , et al. The performance of the European League Against Rheumatism/American College of Rheumatology idiopathic inflammatory myopathies classification criteria in an expert-defined 10 year incident cohort[J]. Rheumatology, 2019, 58(3): 468- 475. doi: 10.1093/rheumatology/key343
12	van den Hoogen F , Khanna D , Fransen J , et al. 2013 classification criteria for systemic sclerosis: An American College of Rheumatology/European League against Rheumatism Collaborative Initiative[J]. Ann Rheum Dis, 2013, 72(11): 1747- 1755. doi: 10.1136/annrheumdis-2013-204424
13	Wielosz E , Dryglewska M , Majdan M . The prevalence and significance of anti-PM/Scl antibodies in systemic sclerosis[J]. Ann Agric Environ Med, 2021, 28(1): 189- 192.
14	Leurs A , Dubucquoi S , Machuron F , et al. Extended myositis-specific and-associated antibodies profile in systemic sclerosis: A cross-sectional study[J]. Joint Bone Spine, 2021, 88(1): 105048. doi: 10.1016/j.jbspin.2020.06.021
15	Lazzaroni MG , Marasco E , Campochiaro C , et al. The clinical phenotype of systemic sclerosis patients with anti-PM/Scl antibo-dies: Results from the EUSTAR cohort[J]. Rheumatology, 2021, 60(11): 5028- 5041. doi: 10.1093/rheumatology/keab152
16	do Amaral Barbosa R , Shinjo SK . Patients with anti-PM/Scl-positive and idiopathic inflammatory myopathy resemble anti-synthetase syndrome[J]. Adv Rheumatol, 2025, 65(1): 9. doi: 10.1186/s42358-025-00441-y
17	Nimmerjahn F , Ravetch JV . Fcgamma receptors as regulators of immune responses[J]. Nat Rev Immunol, 2008, 8(1): 34- 47. doi: 10.1038/nri2206
18	Tsuji H. Pathogenesis and treatment of interstitial lung disease accompanied by anti-melanoma differentiation-associated gene 5-positive idiopathic inflammatory myopathies[J/OL]. Intern Med, 2025, 8(2025-08-28)[2025-08-29]. https://pubmed.ncbi.nlm.nih.gov/40866269.
19	Truchetet ME , Brembilla NC , Chizzolini C . Current concepts on the pathogenesis of systemic sclerosis[J]. Clin Rev Allergy Immunol, 2023, 64(3): 262- 283.
20	Ghobadinezhad F , Ebrahimi N , Mozaffari F , et al. The emerging role of regulatory cell-based therapy in autoimmune disease[J]. Front Immunol, 2022, 13, 1075813. doi: 10.3389/fimmu.2022.1075813

Metrics

Viewed

Full text

Abstract

Cited

Shared

Discussed

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

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

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

[1]	兰静雯, 陈哲, 程永静, 赵丽珂. 老年结缔组织病相关间质性肺病临床特征及抗纤维化治疗的疗效和安全性[J]. 北京大学学报（医学版）, 2025, 57(6): 1101-1106.
[2]	赖展鸿,李嘉辰,贠泽霖,张永刚,张昊,邢晓燕,邵苗,金月波,王乃迪,李依敏,李玉慧,栗占国. 特发性炎性肌病完全临床应答相关因素的单中心真实世界研究[J]. 北京大学学报（医学版）, 2024, 56(2): 284-292.
[3]	李嘉辰,赖展鸿,邵苗,金月波,高小娟,张科,侯儆,张燕英,栗占国,李玉慧. 抗Jo-1抗体在特发性炎性肌病临床分层及疾病谱中的意义[J]. 北京大学学报（医学版）, 2023, 55(6): 958-965.
[4]	游芳凝,罗靓,刘香君,张学武,李春. 未分化结缔组织病患者的妊娠结局、疾病演变及其影响因素[J]. 北京大学学报（医学版）, 2023, 55(6): 1045-1052.
[5]	肖云抒,朱冯赟智,罗澜,邢晓燕,李玉慧,张学武,沈丹华. 88例重叠肌炎的临床及免疫学特征[J]. 北京大学学报（医学版）, 2021, 53(6): 1088-1093.
[6]	魏士雄,黎苏佳,刘毅. 幼年特发性关节炎成人后的临床特点及生物制剂治疗[J]. 北京大学学报（医学版）, 2020, 52(6): 1014-1022.
[7]	姚海红,王旖旎,张霞,赵金霞,贾园,王昭,栗占国. 67例成人巨噬细胞活化综合征的临床特征及治疗转归[J]. 北京大学学报（医学版）, 2019, 51(6): 996-1002.
[8]	王永福,刘媛. 自身抗体在肿瘤及感染性疾病发生、发展中的作用[J]. 北京大学学报（医学版）, 2018, 50(6): 952-955.
[9]	卢昕,张立宁. 肌活检在特发性炎性肌病诊断和临床分型中的价值[J]. 北京大学学报（医学版）, 2018, 50(6): 949-951.
[10]	王昱，周炜，郝燕捷，李光韬，邓雪蓉，赵娟，张卓莉. 跟骨定量超声在筛查结缔组织病患者合并骨质疏松中的应用[J]. 北京大学学报（医学版）, 2013, 45(5): 766-769.
[11]	石宇红, 李茹 , 陈适 , 苏茵 , 贾园. 91例混合性结缔组织病患者的临床特点及转归[J]. 北京大学学报（医学版）, 2012, 44(2): 270-274.
[12]	邓晓莉, 刘湘源, 赵金霞. 弥漫结缔组织病患者心血管并发症的临床特点分析[J]. 北京大学学报（医学版）, 2010, 42(2): 143-146.