特发性炎性肌病自身抗体与临床表型间关联的研究进展

doi:10.16150/j.1671-2870.2022.03.021

摘要/Abstract

摘要：

肌炎特异性自身抗体（myositis specific autoantibody,MSA）对于特发性炎性肌病（idiopathic inflammatory myopathy,IIM）的诊断及分型具有重要的意义。IIM有多种临床表型,包括抗合成酶综合征、免疫介导的坏死性肌病、皮肌炎、临床无肌病性皮肌炎、幼年型皮肌炎、肿瘤相关性肌炎和包涵体肌炎等。不同MSA与以上疾病独特的临床表现及病理表型密切相关,同时部分自身抗体的滴度也与肌炎活动度评分及患者预后间具有一定相关性。因此,MSA检测有助于临床鉴别疾病亚型、实施个性化治疗及判断预后。

关键词: 特发性炎性肌病, 自身抗体, 皮肌炎, 多发性肌炎

Abstract:

Myositis specific autoantibodies(MSA) are important for the diagnosis and classification of idiopathic inflammatory myopathy (IIM). It reveales that there is a close relationship between various types of MSA and unique clinical manifestations as well as pathological phenotypes. The titers of some autoantibodies are also correlated with the disease activity score and prognosis. Therefore, detection of MSA is helpful to the identification of the disease subtypes, personalized treatment selection and the judgement of prognosis in clinical practice. In future, more in-depth researches on MSA are needed to furtherly explore the pathogenic mechanism of the disease.

Key words: Idiopathic inflammatory myopathy, Autoantibodies, Dermatomyositis, Polymyositis

中图分类号:

R593.2

张浩, 池慧慧, 苏禹同, 杨程德. 特发性炎性肌病自身抗体与临床表型间关联的研究进展[J]. 诊断学理论与实践, 2022, 21(03): 408-414.

ZHANG Hao, CHI Huihui, SU Yutong, YANG Chengde. Study on advances in the association between autoantibodies and clinical phenotypes in idiopathic inflammatory myopathy[J]. Journal of Diagnostics Concepts & Practice, 2022, 21(03): 408-414.

图/表 1

表1

肌炎特异性自身抗体及相关临床表型

肌炎特异性自身抗体	肌炎患者中检测阳性率	相关肌炎类型	病理	肺	皮肤	肌肉	肿瘤相关性	其他	预后
抗ARS	成人：21%~30%,儿童：5%~8%	抗合成酶综合征	抗Jo-1阳性以束周坏死多见	多数起病时没有肺部累及的患者,随后会进展为间质性肺病	皮肌炎典型皮疹常见	肌肉累及程度因抗体类型不同	暂无报道	常有雷诺现象、技工手、关节炎、发热等症状	多数预后良好,但合并严重间质性肺病者预后较差
抗MDA5	成人：6%~36%,儿童：8%~28%	皮肌炎,临床无肌病性皮肌炎	血管纤维蛋白沉积为特征的血管病变,伴血管周围炎症	肺部累及多见	皮肌炎典型皮疹常见,可伴皮肤溃疡	肌肉症状常较轻或不累及肌肉	暂无报道	无	合并严重间质性肺病者预后差,死亡率高
抗SAE	成人：2%~8%,儿童：1%	皮肌炎	/	较少累及	皮肌炎典型皮疹常见	起病时较少累及肌肉,随病情进展可逐渐累及	有报道与肺癌、消化系统肿瘤及妇科肿瘤相关	无	预后良好
抗Mi-2	成人：5%~10%,儿童：2%~4%	皮肌炎	可有严重的肌肉纤维化及炎细胞浸润	较少累及	皮肌炎典型皮疹常见	肌肉症状常较严重	有报道	无	治疗反应较好,复发率低
抗NXP2	成人：4%~12%,儿童：16%~23%	皮肌炎,肿瘤相关性肌炎	可见CD4⁺T细胞浸润	较少累及	皮肌炎典型皮疹常见	起病时肌肉症状较重,可伴吞咽困难	有报道	与钙质沉着相关	复发率较高
抗TIF1-γ	成人：4%~13%,儿童：16%~35%	皮肌炎,肿瘤相关性肌炎	/	较少累及	严重皮疹包括向阳疹,红白斑块等	肌肉症状常较轻	与成人（>50岁）恶性肿瘤密切相关	与钙质沉着相关	合并肿瘤的患者预后较差,生存率较低
抗SRP	成人：4%~15%,儿童：1%~4%	免疫介导的坏死性肌病	肌纤维坏死及较少的淋巴细胞或炎症浸润	较少累及	较少出现皮疹且通常不典型	严重且快速进展的对称性近端肌无力症状	暂无报道	可累及心脏	治疗反应常较差,病死率较高
抗HMGCR	成人：6%~10%,儿童：1%	免疫介导的坏死性肌病	肌纤维坏死及较少的淋巴细胞或炎症浸润	较少累及	较少出现皮疹且通常不典型	严重且快速进展的对称性近端肌无力症状	有报道与罹患肿瘤风险增加相关	与他汀暴露关系密切	年轻患者较年长患者预后差
抗cN1A	包涵体肌炎中阳性率35%~50%	包涵体肌炎	可见嗜酸性胞质包涵体	较少累及	皮疹不常见	肌酸激酶水平轻度升高	暂无报道	可见于其他自身免疫疾病	死亡风险增高

表1

参考文献 40

[1]	Witt LJ, Curran JJ, Strek ME. The diagnosis and treatment of antisynthetase syndrome[J]. Clin Pulm Med, 2016, 23(5):218-226. doi: 10.1097/CPM.0000000000000171 URL
[2]	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 URL
[3]	Ueki M, Kobayashi I, Takezaki S, et al. Myositis-specific autoantibodies in Japanese patients with juvenile idiopathic inflammatory myopathies[J]. Mod Rheumatol, 2019, 29(2):351-356. doi: 10.1080/14397595.2018.1452353 URL
[4]	Gupta L, Naveen R, Gaur P, et al. Myositis-specific and myositis-associated autoantibodies in a large Indian cohort of inflammatory myositis[J]. Semin Arthritis Rheum, 2021, 51(1):113-120. doi: 10.1016/j.semarthrit.2020.10.014 URL
[5]	Xu Q, Li QX, Bi FF, et al. The association between myositis-specific autoantibodies and muscle pathologies in idiopathic inflammatory myopathies[J]. Clin Rheumatol, 2021, 40(2):613-624. doi: 10.1007/s10067-020-05274-2 URL
[6]	Mescam-Mancini L, Allenbach Y, Hervier B, et al. Anti-Jo-1 antibody-positive patients show a characteristic necrotizing perifascicular myositis[J]. Brain, 2015, 138(Pt 9):2485-2492. doi: 10.1093/brain/awv192 pmid: 26198592
[7]	Pinal-Fernandez I, Casal-Dominguez M, Huapaya JA, et al. A longitudinal cohort study of the anti-synthetase syndrome: increased severity of interstitial lung disease in black patients and patients with anti-PL7 and anti-PL12 autoantibodies[J]. Rheumatology (Oxford), 2017, 56(6):999-1007. doi: 10.1093/rheumatology/kex021 pmid: 28339994
[8]	Yang Y, Liu Y, Huang L, et al. Clinical Features and cytokine profile in myositis patients with anti-EJ autoantibodies detected by a novel immunoprecipitation assay[J]. Biomed Res Int, 2019, 2019:1856180.
[9]	Ge Y, Li S, Li S, et al. Interstitial lung disease is a major characteristic of anti-KS associated ant-synthetase syndrome[J]. Ther Adv Chronic Dis, 2020, 11:2040622320 968417.
[10]	Zhan X, Yan W, Wang Y, et al. Clinical features of anti-synthetase syndrome associated interstitial lung disease: a retrospective cohort in China[J]. BMC Pulm Med, 2021, 21(1):57. doi: 10.1186/s12890-021-01399-5 pmid: 33579248
[11]	Bergua C, Chiavelli H, Allenbach Y, et al. In vivo pathogenicity of IgG from patients with anti-SRP or anti-HMGCR autoantibodies in immune-mediated necrotising myopathy[J]. Ann Rheum Dis, 2019, 78(1):131-139. doi: 10.1136/annrheumdis-2018-213518 URL
[12]	Betteridge Z, Tansley S, Shaddick G, et al. Frequency, mutual exclusivity and clinical associations of myositis autoantibodies in a combined European cohort of idiopathic inflammatory myopathy patients[J]. J Autoimmun, 2019, 101:48-55. doi: S0896-8411(19)30100-3 pmid: 30992170
[13]	Benveniste O, Drouot L, Jouen F, et al. Correlation of anti-signal recognition particle autoantibody levels with creatine kinase activity in patients with necrotizing myo-pathy[J]. Arthritis Rheum, 2011, 63(7):1961-1971. doi: 10.1002/art.30344 URL
[14]	Suzuki S, Nishikawa A, Kuwana M, et al. Inflammatory myopathy with anti-signal recognition particle antibodies: case series of 100 patients[J]. Orphanet J Rare Dis, 2015, 10:61. doi: 10.1186/s13023-015-0277-y URL
[15]	Liang WC, Uruha A, Suzuki S, et al. Pediatric necroti-zing myopathy associated with anti-3-hydroxy-3-methylglutaryl-coenzyme A reductase antibodies[J]. Rheumatology (Oxford), 2017, 56(2):287-293. doi: 10.1093/rheumatology/kew386 URL
[16]	Tiniakou E, Pinal-Fernandez I, Lloyd TE, et al. More severe disease and slower recovery in younger patients with anti-3-hydroxy-3-methylglutaryl-coenzyme A reductase-associated autoimmune myopathy[J]. Rheumatology (Oxford), 2017, 56(5):787-794. doi: 10.1093/rheumatology/kew470 pmid: 28096458
[17]	Tanboon J, Inoue M, Hirakawa S, et al. Pathologic features of anti-Mi-2 dermatomyositis[J]. Neurology, 2021, 96(3):e448-e459.
[18]	Liang L, Zhang YM, Chen H, et al. Anti-Mi-2 antibodies characterize a distinct clinical subset of dermatomyositis with favourable prognosis[J]. Eur J Dermatol, 2020, 32(5):103-112.
[19]	Ge Y, Lu X, Shu X, et al. Clinical characteristics of anti-SAE antibodies in Chinese patients with dermatomyositis in comparison with different patient cohorts[J]. Sci Rep, 2017, 7(1):188. doi: 10.1038/s41598-017-00240-6 URL
[20]	Hall JC, Casciola-Rosen L, Samedy LA, et al. Anti-melanoma differentiation-associated protein 5-associated dermatomyositis: expanding the clinical spectrum[J]. Arthritis Care Res (Hoboken), 2013, 65(8):1307-1315. doi: 10.1002/acr.21992 URL
[21]	Chen Z, Hu W, Wang Y, et al. Distinct profiles of myositis-specific autoantibodies in Chinese and Japanese patients with polymyositis/dermatomyositis[J]. Clin Rheumatol, 2015, 34(9):1627-1631. doi: 10.1007/s10067-015-2935-9 URL
[22]	Allenbach Y, Uzunhan Y, Toquet S, et al. Different phenotypes in dermatomyositis associated with anti-MDA5 antibody: Study of 121 cases[J]. Neurology, 2020, 95(1):e70-e78.
[23]	Yamaguchi K, Yamaguchi A, Onuki Y, et al. Clinical features of dermatomyositis associated with anti-MDA5 antibodies by age[J]. Mod Rheumatol, 2021, 31(1):177-185. doi: 10.1080/14397595.2020.1740400 URL
[24]	Mamyrova G, Kishi T, Shi M, et al. Anti-MDA5 autoantibodies associated with juvenile dermatomyositis constitute a distinct phenotype in North America[J]. Rheumatology (Oxford), 2021, 60(4):1839-1849. doi: 10.1093/rheumatology/keaa429 pmid: 33140079
[25]	Bermudez J, Heim X, Bertin D, et al. Lung involvement associated with anti-NXP2 autoantibodies in inflammatory myopathies: a French monocenter series[J]. Expert Rev Respir Med, 2020, 14(8):845-850. doi: 10.1080/17476348.2020.1767598 URL
[26]	Sag E, Demir S, Bilginer Y, et al. Clinical features, muscle biopsy scores, myositis specific antibody profiles and outcome in juvenile dermatomyositis[J]. Semin Arthritis Rheum, 2021, 51(1):95-100. doi: 10.1016/j.semarthrit.2020.10.007 URL
[27]	Sung YK, Jung SY, Kim H, et al. Temporal relationship between idiopathic inflammatory myopathies and malignancies and its mortality: a nationwide population-based study[J]. Clin Rheumatol, 2020, 39(11):3409-3416. doi: 10.1007/s10067-019-04782-0 URL
[28]	Best M, Molinari N, Chasset F, et al. Use of anti-transcriptional intermediary factor-1 gamma autoantibody in identifying adult dermatomyositis patients with cancer: a systematic review and meta-analysis[J]. Acta Derm Venereol, 2019, 99(3):256-262. doi: 10.2340/00015555-3091 URL
[29]	Venalis P, Selickaja S, Lundberg K, et al. Association of anti-transcription intermediary factor 1γ antibodies with paraneoplastic rheumatic syndromes other than dermatomyositis[J]. Arthritis Care Res (Hoboken), 2018, 70(4):648-651. doi: 10.1002/acr.23325 URL
[30]	Oldroyd A, Sergeant JC, New P, et al. The temporal relationship between cancer and adult onset anti-transcriptional intermediary factor 1 antibody-positive dermatomyositis[J]. Rheumatology (Oxford), 2019, 58(4):650-655. doi: 10.1093/rheumatology/key357 URL
[31]	Wong VT, So H, Lam TT, et al. Myositis-specific autoantibodies and their clinical associations in idiopathic inflammatory myopathies[J]. Acta Neurol Scand, 2021, 143(2):131-139. doi: 10.1111/ane.13331 URL
[32]	Ichimura Y, Matsushita T, Hamaguchi Y, et al. Anti-NXP2 autoantibodies in adult patients with idiopathic inflammatory myopathies: possible association with malignancy[J]. Ann Rheum Dis, 2012, 71(5):710-713. doi: 10.1136/annrheumdis-2011-200697 pmid: 22258483
[33]	Betteridge Z, Gunawardena H, Chinoy H, et al. Clinical associations of anti-p140 autoantibodies in adult myositis[J]. Ann Rheum Dis, 2010, 69(Suppl3):127.
[34]	Kadoya M, Hida A, Hashimoto Maeda M, et al. Cancer association as a risk factor for anti-HMGCR antibody-positive myopathy[J]. Neurol Neuroimmunol Neuroinflamm, 2016, 3(6):e290. doi: 10.1212/NXI.0000000000000290 URL
[35]	Monseau G, Landon-Cardinal O, Stenzel W, et al. Systematic retrospective study of 64 patients with anti-Mi2 dermatomyositis: a classic skin rash with a necrotizing myositis and high risk of malignancy[J]. J Am Acad Dermatol, 2020, 83(6):1759-1763. doi: 10.1016/j.jaad.2020.03.058 URL
[36]	Petri MH, Satoh M, Martin-Marquez BT, et al. Implications in the difference of anti-Mi-2 and -p155/140 autoantibody prevalence in two dermatomyositis cohorts from Mexico City and Guadalajara[J]. Arthritis Res Ther, 2013, 15(2):R48. doi: 10.1186/ar4207 URL
[37]	Yang H, Peng Q, Yin L, et al. Identification of multiple cancer-associated myositis-specific autoantibodies in idiopathic inflammatory myopathies: a large longitudinal cohort study[J]. Arthritis Res Ther, 2017, 19(1):259. doi: 10.1186/s13075-017-1469-8 URL
[38]	Felice KJ, Whitaker CH, Wu Q, et al. Sensitivity and clinical utility of the anti-cytosolic 5′-nucleotidase 1A (cN1A) antibody test in sporadic inclusion body myositis: Report of 40 patients from a single neuromuscular center[J]. Neuromuscul Disord, 2018, 28(8):660-664. doi: 10.1016/j.nmd.2018.06.005 URL
[39]	Lucchini M, Maggi L, Pegoraro E, et al. Anti-cN1A antibodies are associated with more severe dysphagia in sporadic inclusion body myositis[J]. Cells, 2021, 10(5):1146. doi: 10.3390/cells10051146 URL
[40]	Lilleker JB, Rietveld A, Pye SR, et al. Cytosolic 5′-nucleotidase 1A autoantibody profile and clinical characte-ristics in inclusion body myositis[J]. Ann Rheum Dis, 2017, 76(5):862-868. doi: 10.1136/annrheumdis-2016-210282 pmid: 28122761