* These authors contributed equally to this work
收稿日期: 2024-07-25
网络出版日期: 2024-12-18
基金资助
国家自然科学基金(82371804);北京市自然科学基金(L222017);北京大学人民医院研究与发展基金(RDX2023-03);北京大学人民医院研究与发展基金(RZ2024-02)
版权
Immunological characteristics of patients with anti-synthetase syndrome overlap with rheumatoid arthritis
Received date: 2024-07-25
Online published: 2024-12-18
Supported by
the National Natural Science Foundation of China(82371804);the Beijing Natural Science Foundation(L222017);the Peking University People' s Hospital Scientific Research and Development Foundation(RDX2023-03);the Peking University People' s Hospital Scientific Research and Development Foundation(RZ2024-02)
Copyright
目的: 探究抗合成酶综合征(anti-synthetase syndrome, ASS)重叠类风湿关节炎(rheumatoid arthritis, RA)患者的免疫学特点。方法: 回顾性分析北京大学人民医院住院的104例ASS伴有关节炎患者的资料，包括人口学资料、临床表现(皮疹、肌肉损害等)、实验室检查结果、外周血淋巴细胞亚群和治疗用药，依据患者是否重叠RA进行分组并比较。结果: 104例ASS伴有关节炎的患者中，明确诊断RA的患者占23.1%(24/104例)，ASS重叠RA组患者的快速进展型间质性肺炎(rapid progressive interstitial lung disease, RP-ILD)发生率(41.7% vs. 17.6%，P=0.032)、压痛关节数[10 (7, 14)个vs. 4 (0, 8)个，P＜0.001]、肿胀关节数[4 (2, 8)个vs. 2 (0, 4)个，P=0.012]及骨侵蚀发生率(47.8% vs. 2.5%，P＜0.001)均显著高于非RA组。实验室检查方面，血小板水平[(289.57±68.74)×103/μL vs. (247.94±77.04)×103/μL, P=0.022]、红细胞沉降率[43 (19, 59) mm/h vs. 18 (10, 44) mm/h, P=0.019]和C反应蛋白[19.20 (4.80, 55.36) mg/L vs. 5.68 (1.10, 14.96) mg/L, P=0.006] 在ASS重叠RA组的患者中显著升高。免疫学指标检查显示，与ASS合并关节炎的患者组相比，ASS重叠RA组患者的外周血CLA+Treg细胞[(11.12±4.10)% vs. (17.22±8.49)%，P=0.003]、B细胞[8.56% (4.80%, 11.90%) vs. 14.55% (8.75%, 20.29%)，P=0.025]、自然杀伤(natural killer，NK)细胞[7.56% (4.65%, 13.20%) vs. 13.25% (7.46%, 19.25%)，P=0.045] 的比例显著降低，Naïve Th细胞[(52.66±17.66)% vs. (40.76±14.96)%，P=0.033]的比例显著升高。治疗反应方面，ASS重叠RA组患者的完全临床应答率较低(16.7% vs. 43.8%, P=0.031)。结论: ASS重叠RA患者的肺部及关节受累更严重，治疗应答率低，对此类患者需早期识别并积极干预。
赵亮 , 史成龙 , 马柯 , 赵静 , 王潇 , 邢晓燕 , 莫万星 , 练益瑞 , 高超 , 李玉慧 . 抗合成酶综合征重叠类风湿关节炎患者的免疫学特征[J]. 北京大学学报（医学版）, 2024 , 56(6) : 972 -979 . DOI: 10.19723/j.issn.1671-167X.2024.06.005
Objective: To investigate the clinical and immunological characteristics of anti-synthetase syndrome (ASS) patients overlap with rheumatoid arthritis (RA). Methods: A retrospective analysis was conducted on ASS patients with arthritis who were treated at Peking University People' s Hospital. Data collected included demographic information, clinical manifestations, laboratory features, lymphocyte subsets in peripheral blood, and treatments. The patients with ASS were divided into two groups based on the presence or absence of RA for comparative analysis. Results: A total of 104 ASS patients with arthritis were included, among whom 23.1% (24/104) were diagnosed with RA. The ASS with RA group had a significantly higher incidence of rapidly progressive interstitial lung disease (RP-ILD) (41.7% vs. 17.6%, P=0.032), number of tender joints [10 (7, 14) vs. 4 (0, 8), P < 0.001], number of swollen joints [4 (2, 8) vs. 2 (0, 4), P=0.012], and rate of bone erosion (47.8% vs. 2.5%, P < 0.001) compared with the non-RA group. Levels of platelets [(289.57±68.74)×103/μL vs. (247.94±77.04)×103/μL, P=0.022], erythrocyte sedimentation rate (ESR) [43 (19, 59) mm/h vs. 18 (10, 44) mm/h, P=0.019], and C-reactive protein (CRP) [19.20 (4.80, 55.36) mg/L vs. 5.68 (1.10, 14.96) mg/L, P=0.006] were found significantly higher in the ASS with RA group than those in non-RA group. Analysis of immune cells in peripheral blood mononuclear cell (PBMC) showed that significantly decreased proportions of CLA+ Treg cells [(11.12±4.10)% vs. (17.22±8.49)%, P=0.003], B cells [8.56% (4.80%, 11.90%) vs. 14.55% (8.75%, 20.29%), P=0.025], and natural killer (NK) cells [7.56% (4.65%, 13.20%) vs. 13.25% (7.46%, 19.25%), P=0.045] in the overlap group compared with non-RA group. Proportion of Naïve Th cells [(52.66±17.66)% vs. (40.76±14.96)%, P=0.033)] was significantly increased in overlap group compared with non-RA group. Overlap group had lower rate of complete clinical response than non-RA group (16.7% vs. 43.8%, P=0.031). Conclusion: Among ASS patients with arthritis, those with RA have more severe lung and joint involvement and a lower treatment response rate, highlighting the need for early recognition and aggressive intervention.
| 1 | Marguerie C , Bunn CC , Beynon HL , et al. Polymyositis, pulmonary fibrosis and autoantibodies to aminoacyl-tRNA synthetase enzymes[J]. Q J Med, 1990, 77 (282): 1019- 1038. |
| 2 | Aggarwal R , Cassidy E , Fertig N , et al. Patients with non-Jo-1 anti-tRNA-synthetase autoantibodies have worse survival than Jo-1 positive patients[J]. Ann Rheum Dis, 2014, 73 (1): 227- 232. |
| 3 | Hervier B , Devilliers H , Stanciu R , et al. Hierarchical cluster and survival analyses of antisynthetase syndrome: Phenotype and outcome are correlated with anti-tRNA synthetase antibody specificity[J]. Autoimmun Rev, 2012, 12 (2): 210- 217. |
| 4 | Labrador-Horrillo M , Martinez MA , Selva-O'Callaghan A , et al. Anti-cyclic citrullinated peptide and anti-keratin antibodies in patients with idiopathic inflammatory myopathy[J]. Rheumatology (Oxford), 2009, 48 (6): 676- 679. |
| 5 | Cavagna L , Nuno L , Scirè CA , et al. Clinical spectrum time course in anti Jo-1 positive antisynthetase syndrome: Results from an international retrospective multicenter study[J]. Medicine (Baltimore), 2015, 94 (32): e1144. |
| 6 | Lekieffre M , Gallay L , Landon-Cardinal O , et al. Joint and muscle inflammatory disease: A scoping review of the published evidence[J]. Semin Arthritis Rheum, 2023, 61, 152227. |
| 7 | Marco JL , Collins BF . Clinical manifestations and treatment of antisynthetase syndrome[J]. Best Pract Res Clin Rheumatol, 2020, 34 (4): 101503. |
| 8 | Connors GR , Christopher-Stine L , Oddis CV , et al. Interstitial lung disease associated with the idiopathic inflammatory myopathies: What progress has been made in the past 35 years?[J]. Chest, 2010, 138 (6): 1464- 1474. |
| 9 | Aletaha D , Neogi T , Silman AJ , et al. 2010 rheumatoid arthritis classification criteria: An American College of Rheumatology/European League Against Rheumatism collaborative initiative[J]. Ann Rheum Dis, 2010, 69 (9): 1580- 1588. |
| 10 | Oddis CV , Rider LG , Reed AM , et al. International consensus guidelines for trials of therapies in the idiopathic inflammatory myopathies[J]. Arthritis Rheum, 2005, 52 (9): 2607- 2615. |
| 11 | Aggarwal R , Rider LG , Ruperto N , et al. 2016 American College of Rheumatology/European League Against Rheumatism criteria for minimal, moderate, and major clinical response in adult dermatomyositis and polymyositis: An International Myositis Assessment and Clinical Studies Group/Paediatric Rheumatology International Trials Organisation collaborative initiative[J]. Ann Rheum Dis, 2017, 76 (5): 792- 801. |
| 12 | 赖展鸿, 李嘉辰, 贠泽霖, 等. 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. |
| 13 | Li Y , Gao X , Li Y , et al. Predictors and mortality of rapidly progressive interstitial lung disease in patients with idiopathic inflammatory myopathy: A series of 474 patients[J]. Front Med (Lausanne), 2020, 7, 363. |
| 14 | Jablonski R , Bhorade S , Strek ME , et al. Recognition and ma-nagement of myositis-associated rapidly progressive interstitial lung disease[J]. Chest, 2020, 158 (1): 252- 263. |
| 15 | Go DJ , Park JK , Kang EH , et al. Survival benefit associated with early cyclosporine treatment for dermatomyositis-associated interstitial lung disease[J]. Rheumatol Int, 2016, 36 (1): 125- 131. |
| 16 | Xu Y , Yang CS , Li YJ , et al. Predictive factors of rapidly progressive-interstitial lung disease in patients with clinically amyopathic dermatomyositis[J]. Clin Rheumatol, 2016, 35 (1): 113- 116. |
| 17 | Milovanovic M , Nilsson E , J?remo P . Relationships between platelets and inflammatory markers in rheumatoid arthritis[J]. Clin Chim Acta, 2004, 343 (1/2): 237- 240. |
| 18 | Yazici S , Yazici M , Erer B , et al. The platelet indices in patients with rheumatoid arthritis: Mean platelet volume reflects disease activity[J]. Platelets, 2010, 21 (2): 122- 125. |
| 19 | Liu Y , Jiang H , Kang T , et al. Platelets-related signature based diagnostic model in rheumatoid arthritis using WGCNA and machine learning[J]. Front Immunol, 2023, 14, 1204652. |
| 20 | Rosengren S , Corr M , Boyle DL . Platelet-derived growth factor and transforming growth factor beta synergistically potentiate inflammatory mediator synthesis by fibroblast-like synoviocytes[J]. Arthritis Res Ther, 2010, 12 (2): 1- 11. |
| 21 | Lefèvre S , Schwarz M , Meier FMP , et al. Disease-specific effects of matrix and growth factors on adhesion and migration of rheumatoid synovial fibroblasts[J]. J Immunol, 2017, 198 (12): 4588- 4595. |
| 22 | Brown AJ , Sepuru KM , Sawant KV , et al. Platelet-derived chemokine CXCL7 dimer preferentially exists in the glycosaminoglycan-bound form: Implications for neutrophil-platelet crosstalk[J]. Front Immunol, 2017, 8, 1248. |
| 23 | Gáspár K , Baráth S , Nagy G , et al. Regulatory T-cell subsets with acquired functional impairment: Important indicators of disease severity in atopic dermatitis[J]. Acta Derm Venereol, 2015, 95 (2): 151- 155. |
| 24 | Li J , Sun F , Zhu D , et al. Deficiency of peripheral CLA(+) Tregs and clinical relevance in Behcet' s syndrome[J]. Arthritis Res Ther, 2024, 26 (1): 76. |
| 25 | Chalan P , Bijzet J , Kroesen BJ , et al. Altered natural killer cell subsets in seropositive arthralgia and early rheumatoid arthritis are associated with autoantibody status[J]. J Rheumatol, 2016, 43 (6): 1008- 1016. |
| 26 | Aggarwal A , Sharma A , Bhatnagar A . Role of cytolytic impairment of natural killer and natural killer T-cell populations in rheumatoid arthritis[J]. Clin Rheumatol, 2014, 33 (8): 1067- 1078. |
| 27 | S?derstr?m K , Stein E , Colmenero P , et al. Natural killer cells trigger osteoclastogenesis and bone destruction in arthritis[J]. Proc Natl Acad Sci USA, 2010, 107 (29): 13028- 13033. |
| 28 | Romas E , Gillespie MT , Martin TJ . Involvement of receptor activator of NF kappa B ligand and tumor necrosis factor-alpha in bone destruction in rheumatoid arthritis[J]. Bone, 2002, 30 (2): 340- 346. |
| 29 | Leipe J , Grunke M , Dechant C , et al. Role of Th17 cells in human autoimmune arthritis[J]. Arthritis Rheum, 2010, 62 (10): 2876- 2885. |
| 30 | Takayanagi H , Ogasawara K , Hida S , et al. T-cell-mediated regulation of osteoclastogenesis by signalling cross-talk between RANKL and IFN-gamma[J]. Nature, 2000, 408 (6812): 600- 605. |
| 31 | Harrington LE , Hatton RD , Mangan PR , et al. Interleukin 17-producing CD4+ effector T cells develop via a lineage distinct from the T helper type 1 and 2 lineages[J]. Nat Immunol, 2005, 6 (11): 1123- 1132. |
| 32 | Lundberg IE , Fujimoto M , Vencovsky J , et al. Idiopathic inflammatory myopathies[J]. Nat Rev Dis Primers, 2021, 7 (1): 86. |
| 33 | Witt LJ , Curran JJ , Strek ME . The diagnosis and treatment of antisynthetase syndrome[J]. Clin Pulm Med, 2016, 23 (5): 218- 226. |
| 34 | Baumann Benvenuti F , Dudler J . Long-lasting improvement of refractory antisynthetase syndrome with tocilizumab: A report of two cases[J]. RMD Open, 2023, 9 (4): e003599. |
| 35 | Narváez J , Ca?adillas E , Castellví I , et al. Rituximab in the treatment of progressive interstitial lung disease associated with the antisynthetase syndrome[J]. Arthritis Res Ther, 2024, 26 (1): 122. |
| 36 | Smolen JS , Beaulieu A , Rubbert-Roth A , et al. Effect of interleukin-6 receptor inhibition with tocilizumab in patients with rheumatoid arthritis (OPTION study): A double-blind, placebo-controlled, randomised trial[J]. Lancet, 2008, 371 (9617): 987- 997. |
/
| 〈 |
|
〉 |
