Sennett Rachel, Jama Burhan M, Hinds Brian, Tzachanis Dimitrios, Morris Gerald P, Marsch Amanda F
Department of Dermatology, University of California San Diego School of Medicine, La Jolla, CA, United States.
Department of Pathology, University of California San Diego School of Medicine, La Jolla, CA, United States.
Int J Womens Dermatol. 2020 May 22;6(4):311-317. doi: 10.1016/j.ijwd.2020.05.009. eCollection 2020 Sep.
Hematopoietic stem cell transplant is a crucial intervention to definitively treat many hematopoietic malignancies, but it carries great risks of morbidity and mortality often associated with graft-versus-host disease (GVHD). Acute and chronic GVHD are distinct entities, defined by a combination of historical, clinical, and pathologic data, but both are generally thought to stem from self-propagating aberrantly activated immune cells inflicting end organ damage, with the potential to cause significant illness or even death. Event-free survival rates after hematopoietic stem cell transplant continue to improve each year, but GVHD remains a major hurdle in improving the efficacy and safety of transplant.
Recent studies demonstrating tissue-specific immune effector phenotypes underscore the need for a deeper understanding of the cellular and molecular pathways driving the destruction of target tissues in patients with acute GVHD.
Samples were collected from lesional and unaffected skin in five patients with acute cutaneous GHVD. Fresh tissue was processed for fluorescence-activated cell sorting and analysis of macrophages and lymphocytes.
The percentage of lymphocytes and macrophages as a representation of total cells varied among patients and was not always consistent between lesional and unaffected sites. The heterogeneity in immune cell profiling observed in patients in this study could reflect the diverse demographics, conditioning, and transplant conditions of each individual.
This study provides initial insight into the underlying molecular mechanisms of cutaneous GVHD progression and paves the way for additional studies to examine the cellular and molecular landscape in greater detail.
造血干细胞移植是根治多种造血系统恶性肿瘤的关键干预措施,但它具有很高的发病和死亡风险,且常常与移植物抗宿主病(GVHD)相关。急性和慢性GVHD是不同的实体,由历史、临床和病理数据综合定义,但一般都认为它们源于自我增殖的异常激活免疫细胞对终末器官造成损害,有可能导致严重疾病甚至死亡。造血干细胞移植后的无事件生存率逐年持续提高,但GVHD仍然是提高移植疗效和安全性的主要障碍。
近期研究表明了组织特异性免疫效应表型,这凸显了深入了解驱动急性GVHD患者靶组织破坏的细胞和分子途径的必要性。
从5例急性皮肤GVHD患者的病变皮肤和未受影响的皮肤中采集样本。对新鲜组织进行处理,用于荧光激活细胞分选以及巨噬细胞和淋巴细胞分析。
淋巴细胞和巨噬细胞占总细胞的百分比在患者之间有所不同,且在病变部位和未受影响部位之间并不总是一致。本研究中观察到的患者免疫细胞谱的异质性可能反映了每个个体不同的人口统计学特征、预处理情况和移植条件。
本研究初步洞察了皮肤GVHD进展的潜在分子机制,为进一步更详细地研究细胞和分子情况的其他研究铺平了道路。