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同种异体间充质干细胞治疗系统性红斑狼疮患者临床反应的预后因素

Prognostic Factors for Clinical Response in Systemic Lupus Erythematosus Patients Treated by Allogeneic Mesenchymal Stem Cells.

作者信息

Wen Lihui, Labopin Myriam, Badoglio Manuela, Wang Dandan, Sun Lingyun, Farge-Bancel Dominique

机构信息

Department of Rheumatology and Immunology, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing 210008, China.

Unité de Médecine Interne: Maladies Auto-Immunes et Pathologie Vasculaire (UF 04), Centre de Référence des Maladies Auto-Immunes Systémiques Rares d'Ile-de-France (Site Constitutif), Filière FAI2R, Hôpital Saint-Louis Assistance Publique Hôpitaux de Paris (AP-HP), 1, Avenue Claude-Vellefaux, 75010 Paris, France.

出版信息

Stem Cells Int. 2019 May 2;2019:7061408. doi: 10.1155/2019/7061408. eCollection 2019.

Abstract

Systemic lupus erythematosus (SLE) is an autoimmune disease with a broad range of clinical manifestations and a heterogeneous disease course. There is no cure for SLE, but current standard pharmacotherapies can improve disease prognosis in most patients. However, some patients are refractory to conventional treatments and require alternative treatment options. The present study is aimed at identifying predictors of clinical response to allogeneic bone marrow-derived or umbilical cord-derived mesenchymal stem cell (BM-/UC-MSC) transplant in SLE. All adult patients identified in the Nanjing database with an SLE Disease Activity Index (SLEDAI) score ≥ 8 at baseline that had undergone MSC transplant and who had at least 1 year of follow-up after one or two successive intravenous injections of allogeneic BM-/UC-MSCs (1 million/kg) were analyzed. SLE symptoms and SLEDAI were assessed at baseline and during follow-up to determine low disease activity (LDA) and clinical remission (CR) at 1, 3, 6, and 12 months. Sixty-nine patients were included in the study, with a median (range) SLEDAI of 13 (8-34) at baseline. Among the 69 patients, 40 (58%) achieved LDA and 16 (23%) achieved CR with a SLEDAI of 9 (4-20), 8 (0-16), 6 (0-18), and 5 (0-18) after 1, 3, 6, and 12 months, respectively. Older age ( = 0.006) and no arthralgia/arthritis at baseline ( = 0.03) were associated with a higher rate of LDA. Achieving CR was associated with older age ( = 0.033), no arthralgia/arthritis at baseline ( = 0.001), and no prior use of cyclophosphamide ( = 0.003) or hydroxychloroquine ( = 0.016). Future studies using unique immunosuppressive regimens and allogeneic MSC sources will further elucidate determinants of clinical response to MSC transplant in SLE.

摘要

系统性红斑狼疮(SLE)是一种自身免疫性疾病,临床表现广泛,病程异质性强。SLE无法治愈,但目前的标准药物治疗可改善大多数患者的疾病预后。然而,一些患者对传统治疗无效,需要其他治疗选择。本研究旨在确定系统性红斑狼疮患者对同种异体骨髓来源或脐带来源间充质干细胞(BM-/UC-MSC)移植临床反应的预测因素。分析了南京数据库中所有基线SLE疾病活动指数(SLEDAI)评分≥8、接受过MSC移植且在连续一或两次静脉注射同种异体BM-/UC-MSCs(100万/kg)后至少随访1年的成年患者。在基线和随访期间评估SLE症状和SLEDAI,以确定1、3、6和12个月时的低疾病活动度(LDA)和临床缓解(CR)。69例患者纳入研究,基线时SLEDAI中位数(范围)为13(8-34)。在这69例患者中,分别在1、3、6和12个月后,40例(58%)达到LDA,16例(23%)达到CR,SLEDAI分别为9(4-20)、8(0-16)、6(0-18)和5(0-18)。年龄较大(P = 0.006)和基线时无关节痛/关节炎(P = 0.03)与较高的LDA发生率相关。实现CR与年龄较大(P = 0.033)、基线时无关节痛/关节炎(P = 0.001)以及既往未使用环磷酰胺(P = 0.003)或羟氯喹(P = 0.016)相关。未来使用独特免疫抑制方案和同种异体MSC来源的研究将进一步阐明系统性红斑狼疮患者对MSC移植临床反应的决定因素。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7ac8/6525791/4f9faaa2adf6/SCI2019-7061408.001.jpg

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