免疫性血小板减少症与持续紊乱的纤维化相关血清标志物谱相关，但骨髓纤维化程度较低：一项关于促血小板生成素受体激动剂治疗的 2 年观察性研究。
Immune thrombocytopenia is associated with persistently deranged fibrosis-related seromarker profiles but low bone marrow fibrosis grades: A 2-year observational study on thrombopoietin receptor agonist treatment.
机构信息
a Departments of Research , Medicine and Oncology, Østfold Hospital Trust, Grålum, Norway.
b Departments of Hematology, Institute of clinical medicine , Oslo University , Oslo Norway.
出版信息
Platelets. 2019;30(2):222-228. doi: 10.1080/09537104.2017.1411586. Epub 2018 Jan 2.
Bone marrow (BM) fibrosis is a potential side effect of thrombopoietin receptor agonist (TPO-RA) treatment. We aimed to investigate stromal seromarker profiles and growth factors in order to elucidate pathogenic and dynamic aspects of immune thrombocytopenia (ITP)-related BM fibrosis before and during TPO-RA treatment. Connective tissue metabolites [procollagen I and III peptides (PINP/PIIINP); hyaluronan (HYA), C-terminal-telopeptide (ICTP), and fibrosis-related growth factors (transforming growth factor-beta (TGF-beta), HGF, basic fibroblast growth factor)] were measured in blood samples acquired before initiation of TPO-RA and subsequently at 6-month intervals for up to 2 years. BM fibrosis was graded MF-0 in 8 (18%), MF-1 30 (65%), and MF-2 8 (18%) in the last available BM biopsy. In the 21 patients having more than one biopsy, the grade of fibrosis from the first to the last available biopsy decreased in 2 (10%), remained unchanged in 15 (71%), and increased in 4 (19%). Pretreatment levels of PIIINP, PINP, ICTP, and HYA were significantly increased in ITP versus controls. PINP, PIIINP, and HYA decreased on TPO-RA; ICTP remained unchanged. PINP:ICTP was lower before and during treatment compared to controls. Pretreatment, TGF-beta was lower than in controls; HGF exhibited the opposite pattern. HYA, ICTP, and TGF-beta tended to increase while PINP and platelet-derived growth factor tended to decrease with increasing fibrosis grade. In conclusion, ITP is associated with deranged patterns of extracellular matrix seromarkers and growth factors, indicating that BM stromal remodeling is enhanced. During TPO-RA treatment for up to 2 years, this profile was partially reversed while mild BM reticulin fibrosis was still present in the majority of patients. These observations likely reflect a BM injury by autoimmunity that is modified by TPO-RA.
骨髓（BM）纤维化是血小板生成素受体激动剂（TPO-RA）治疗的潜在副作用。我们旨在研究基质血清标志物谱和生长因子，以阐明免疫性血小板减少症（ITP）相关 BM 纤维化在 TPO-RA 治疗前和治疗期间的发病和动态方面。在开始使用 TPO-RA 之前和之后，每 6 个月测量一次血液样本中的结缔组织代谢物[前胶原 I 和 III 肽（PINP/PIIINP）；透明质酸（HYA），C 端末端肽（ICTP）和纤维化相关生长因子（转化生长因子-β（TGF-β），HGF，碱性成纤维细胞生长因子）]，长达 2 年。在最后一次可获得的 BM 活检中，8 例（18％）纤维化程度为 MF-0，30 例（65％）为 MF-1，8 例（18％）为 MF-2。在 21 例有多个活检的患者中，从第一次到最后一次可获得的活检，纤维化程度降低了 2 例（10％），保持不变 15 例（71％），增加了 4 例（19％）。与对照组相比，ITP 患者的 PIIINP、PINP、ICTP 和 HYA 预处理水平显着升高。TPO-RA 后 PINP、PIIINP 和 HYA 降低；ICTP 保持不变。与对照组相比，TPO-RA 治疗前后的 PINP：ICTP 较低。预处理时 TGF-β低于对照组；HGF 表现出相反的模式。HYA、ICTP 和 TGF-β 趋于增加，而 PINP 和血小板衍生生长因子趋于减少，纤维化程度增加。总之，ITP 与细胞外基质血清标志物和生长因子的紊乱模式相关，表明 BM 基质重塑增强。在长达 2 年的 TPO-RA 治疗期间，这种情况部分得到逆转，而大多数患者仍存在轻度 BM 网状纤维纤维化。这些观察结果可能反映了由 TPO-RA 修饰的自身免疫引起的 BM 损伤。
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