目的: 探讨缓解性血清阴性对称性滑膜炎伴凹陷性水肿(Remissive seronegative symmetric synovitis with depressed edema,RS3PE)患者血清中基质金属蛋白酶3(matrix metallopro-teinase-3,MMP-3)、基质金属蛋白酶抑制剂1(tissue inhibitor of metalloproteinases-1,TIMP1)、基质金属蛋白酶抑制剂2(tissue inhibitor of metalloproteinases-2,TIMP2)、血清骨桥素1(serum bone bridging protein 1,SPP1)及纤溶酶原(plasminogen,PLG)与疾病活动程度的相关性。方法: 收集2020年5月~2021年7月包头医学院第二附属医院风湿免疫科诊治的RS3PE综合征患者21例(RS3PE组),正常健康体检者30例为对照组(CON组),两组均采用实时荧光定量PCR(qRT-PCR)和酶联免疫吸附试验(ELISA)法检测血清中MMP-3、TIMP1、TIMP2、SPP1及PLG基因和蛋白的表达水平。并对两组受试者类风湿因子(rheumatoid factor,RF)、血沉(erythrocyte sedimentation rate,ESR)和C-反应蛋白(C-reactive protein,CRP)、X线表现、磁共振成像(MRI)表现进行总结归纳。结果: 与CON组相比,RS3PE组ESR、CRP、MMP-3、TIMP1、TIMP2、SPP1表达水平明显升高(P＜0.01),PLG表达水平无明显变化(P＞0.05);MMP-3、TIMP1、TIMP2、SPP1表达水平与ESR、CRP均呈明显正相关。结论: 在RS3PE患者血清中MMP-3、TIMP1、TIMP2、SPP1表达水平明显增加,其表达水平与ESR和CRP水平呈明显正相关,提示MMP-3、TIMP1、TIMP2、SPP1可能参与了RS3PE的发生发展,与疾病活动程度密切相关。
Objective: To investigate the correlation of serum matrix metallopro-teinase-3 (MMP-3), tissue inhibitor of metalloproteinases-1 (TIMP1), tissue inhibitor of metalloproteinases-2 (TIMP2), serum bone bridging protein 1 (SPP1) and plasminogen (PLG) with disease activity in patients with remissive seronegative symmetric synovitis with depression edema (RS3PE). Methods: Twenty-one patients (RS3PE group) with RS3PE syndrome diagnosed and treated in the Department of Rheumatology and Immunology, Second Affiliated Hospital of Baotou Medical College from May 2020 to July 2021 were collected, and 30 healthy people were selected as the control group (CON group). The expression levels of MMP-3, TIMP1, TIMP2, SPP1 and PLG genes and proteins in serum were detected by real-time quantitative PCR (qRT-PCR) and enzyme-linked immunosorbent assay (ELISA) in both groups. The rheumatoid factor (RF), erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP), X-ray manifestations and magnetic resonance imaging (MRI) manifestations of the two groups were summarized. Results: Compared with the CON group, the expression levels of ESR, CRP, MMP-3, TIMP1, TIMP2, and SPP1 were significantly higher in the RS3PE group (P＜0.01), and there was no significant change in PLG expression levels (P＞0.05); the expression levels of MMP-3, TIMP1, TIMP2, and SPP1 were significantly and positively correlated with ESR and CRP. Conclusion: The expression levels of MMP-3, TIMP1, TIMP2 and SPP1 in serum of patients with RS3PE are significantly increased, and their expression levels are significantly positively correlated with ESR and CRP levels, suggesting that MMP-3, TIMP1, TIMP2 and SPP1 may be involved in the occurrence and development of RS3PE, and are closely related to the degree of disease activity.
[1] Alba Gago I, Vicente López O, Pérez Alonso-Castrillo M. RS3PE:A presentation of a case[J]. Aten Primaria,2021,53(3):101978.
[2] 田真,赵义. 50例缓和性血清阴性对称性滑膜炎伴凹陷性水肿综合征的临床特点分析[J]. 临床内科杂志,2019,36(7):472-475.
[3] Gauci ML,Baroudjian B,Laly P,et al. Remitting seronegative symmetrical synovitis with pitting edema (RS3PE) syndrome induced by nivolumab[J]. Semin Arthritis Rheum,2017,47(2):281-287.
[4] Yajima S,Ooeda T,Inoue M,et alParaneoplastic remitting seronegative symmetrical synovitis with pitting edema(RS3PE),improved following surgical resection of prostatic carcinoma:A case report[J]. Urol Case Rep,2020,32:101232.
[5] Origuchi T,Arima K,Kawashiri SY,et al. High serum matrix metalloproteinase 3 is characteristic of patients with paraneoplastic remitting seronegative symmetrical synovitis with pitting edema syndrome[J]. Mod Rheumatol,2012, 22(4):584-858.
[6] Kenzaka T. The Relationship between remitting seronegative symmetrical synovitis with pitting edema and vascular endothelial growth factor and matrix metalloproteinase 3[J]. Intern Med,2020,59(8):1021-1022.
[7] Kawashiri SY,Nakano M,Kawakami A,et al. Monitoring of therapeutic efficacy in a patient with RS3PE syndrome by serologic variables and radiographic methods[J]. Rheumatol Int,2010,30(12):1677-1680.
[8] Kato T,Ubara Y,Sawa N,et al. An abrupt onset of seropositive polyarthritis with prominent distal tenosynovitis concomitant with bronochiolitis obliterans organizing pneumonia (BOOP):consideration of the relationship with RS3PE syndrome[J]. Intern Med,2004,43(2):143-147.
[9] Mccarty DJ,O'Dufly JD,Pearson L,et al. Remitting seronegative symmetrical synovitis with pitting edema. RS3PE syndrome[J]. JAMA,1985,254(19):2763-2767.
[10] Lakhmalla M,Dahiya DS,Kichloo A,et al. Remitting seronegative symmetricalsynovitis with pitting edema:a review[J]. J Investig Med,2021,69(1):86-90.
[11] Aoshima Y, Karayama M, Sagisaka S, et al. Synchronous occurrence of bazex syndrome and remitting seronegative symmetrical synovitis with pitting edema syndrome in a patient with lung cancer [J]. Intern Med,2019, 58(22):3267-3271.
[12] Marto G, Klitna Z, Biléu MC,et al. Remitting seronegative symmetrical synovitis with pitting oedema syndrome, associated with prostate adenocarcinoma: a case report [J]. Acta Reumatol Port,2010, 35(3):358-60.
[13] Matsunaga T, Izumi Y, Iwanaga N,et al. Myelodysplastic syndrome precedes the onset of remitting seronegative symmetrical synovitis with pitting edema (RS3PE) syndrome [J]. Tohoku J Exp Med,2015, 235(1):47-52.
[14] Curran S,Dundas SR,Buxton J,et al. Matrix metalloproteinase/tissue inhibitors of matrix metalloproteinase phenotype identifies poor prognosis colorectal cancers[J]. Clin Cancer Res,2004,10(24):8229-8234.
[15] Zucker S,Vacirca J. Role of matrix metalloproteinases (MMPs) in colorectal cancer[J]. Cancer Metastasis Rev,2004,23(1-2):101-117.
[16] Gohji K,Fujimoto N,Komiyama T,et al. Elevation of serum levels of matrix metalloproteinase-2 and -3 as new predictors of recurrence in patients with urothelial carcinoma[J]. Cancer,1996,78(11):2379-2387.
[17] Behm C,Nemec M,Weissinger F,et al. MMPs and TIMPs expression levels in the periodontal ligament during orthodontic tooth movement:a systematic review of in vitro and in vivo studies[J]. Int J Mol Sci,2021,22(13):6967.
[18] Li K,Tay FR,Yiu CKY. The past,present and future perspectives of matrix metalloproteinase inhibitors[J]. Pharmacol Ther,2020,207:107465.
[19] Bokarewa M,Dahlberg L,Tarkowski A. Expression and functional properties of antibodies to tissue inhibitors of metalloproteinases (TIMPs) in rheumatoid arthritis[J]. Arthritis Res Ther,2005,7(5):R1014-1022.
[20] Nazemisalman B,Sajedinejad N,Darvish S,et al. Evaluation of inductive effects of different concentrations of cyclosporine A on MMP-1,MMP-2,MMP-3,TIMP-1, and TIMP-2 in fetal and adult human gingival fibroblasts[J]. J Basic Clin Physiol Pharmacol,2019,30(3):23-28.
[21] Katrib A,Smith MD,Ahern MJ,et al. Reduced chemokine and matrix metalloproteinase expression in patients with rheumatoid arthritis achieving remission[J]. J Rheumatol,2003,30(1):10-21.
[22] Deng G,Zeng F,Su J,et al. BET inhibitor suppresses melanoma progressionviathe noncanonical NF-κB/SPP1 pathway[J]. Theranostics, 2020,10(25):11428-11443.
[23] Chen JH,Chen YC,Mao CL,et al. Association between secreted phosphoprotein-1 (SPP1) polymorphisms and low bone mineral density in women[J]. PLoS One,2014,9(5):e97428.
[24] 王丽芳,刘伟,董鹏,等. 缓和性血清阴性对称性滑膜炎伴凹陷性水肿综合征患者抗骨质疏松治疗价值初探[J]. 中华风湿病学杂志,2020,24(12):817-819.
