Department of Medicine, Division of Rheumatology, Medical University of South Carolina, Charleston, South Carolina, USA.
Department of Medicine, Division of Hematology/Oncology, Ohio State Wexner Medical Center, Columbus, Ohio, USA.
Lupus Sci Med. 2022 Jul;9(1). doi: 10.1136/lupus-2022-000704.
Reports of clinical improvement following mesenchymal stromal cell (MSC) infusions in refractory lupus patients at a single centre in China led us to perform an explorative phase I trial of umbilical cord derived MSCs in patients refractory to 6 months of immunosuppressive therapy.
Six women with a SLEDAI >6, having failed standard of care therapy, received one intravenous infusion of 1×10 MSCs/kg of body weight. They maintained their current immunosuppressives, but their physician was allowed to adjust corticosteroids initially for symptom management. The clinical endpoint was an SRI of 4 with no new British Isles Lupus Activity Guide (BILAG) As and no increase in Physician Global Assessment score of >0.3 with tapering of prednisone to 10 mg or less by 20 weeks.
Of six patients, five (83.3%; 95% CI 35.9% to 99.6%) achieved the clinical endpoint of an SRI of 4. Adverse events were minimal. Mechanistic studies revealed significant reductions in CD27IgD double negative B cells, switched memory B cells and activated naïve B cells, with increased transitional B cells in the five patients who met the endpoint. There was a trend towards decreased autoantibody levels in specific patients. Two patients had increases in their Helios+Treg cells, but no other significant T cell changes were noted. GARP-TGFβ complexes were significantly increased following the MSC infusions. The B cell changes and the GARP-TGFβ increases significantly correlated with changes in SLEDAI scores.
This phase 1 trial suggests that umbilical cord (UC) MSC infusions are very safe and may have efficacy in lupus. The B cell and GARP-TGFβ changes provide novel insight into mechanisms by which MSCs may impact disease.
NCT03171194.
在中国的一家中心，报告显示间充质基质细胞（MSC）输注后难治性狼疮患者的临床改善，这促使我们对 6 个月免疫抑制治疗无效的患者进行脐带衍生 MSC 的探索性 I 期试验。
6 名女性 SLEDAI >6，标准治疗失败，接受 1×10 MSCs/kg 的静脉输注。他们维持当前的免疫抑制剂，但允许他们的医生最初根据症状管理调整皮质类固醇。临床终点是 SRI 为 4，没有新的不列颠群岛狼疮活动指南（BILAG）As，并且在 20 周内泼尼松减量至 10mg 或更少时，医生全球评估评分增加不超过 0.3。
在 6 名患者中，有 5 名（83.3%；95%CI 35.9%至 99.6%）达到 SRI 为 4 的临床终点。不良事件很少。机制研究显示，在达到终点的 5 名患者中，CD27IgD 双阴性 B 细胞、转换记忆 B 细胞和活化的幼稚 B 细胞显著减少，过渡性 B 细胞增加。在特定患者中，自身抗体水平呈下降趋势。两名患者的 Helios+Treg 细胞增加，但未观察到其他显著的 T 细胞变化。GARP-TGFβ 复合物在 MSC 输注后显著增加。B 细胞变化和 GARP-TGFβ 增加与 SLEDAI 评分的变化显著相关。
这项 I 期试验表明，脐带（UC）MSC 输注非常安全，并且可能对狼疮有效。B 细胞和 GARP-TGFβ 的变化为 MSC 可能影响疾病的机制提供了新的见解。
NCT03171194。
