Zaninoni Anna, Imperiali Francesca G, Cattaneo Alessandra, Soverini Giulia, Binda Francesca, Porretti Laura, Cortelezzi Agostino, Barcellini Wilma
U.O. Oncoematologia and, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milano.
Servizio di Citofluorimetria, U.O. Laboratorio Centrale di Analisi Chimico Cliniche e Microbiologiche Dipartimento dei Servizi, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milano.
Transfusion. 2016 Aug;56(8):2037-41. doi: 10.1111/trf.13652. Epub 2016 May 27.
Low-risk myelodysplastic syndromes (MDS) show several immunologic abnormalities, including increased frequency of autoimmune manifestations and/or overt autoimmune diseases, whose prognostic significance still remains controversial.
We studied the presence of erythroblast antibodies in mitogen-stimulated bone marrow (BM) cultures of 70 patients with early-stage MDS (refractory anemia and refractory anemia with ringed sideroblasts).
Sixty-six percent of patients showed positive erythroblast antibodies, along with BM erythroid hyperplasia and a hemolytic picture in the peripheral blood. Supernatants from positive cultures induced an increase of overall cellularity, the appearance of erythroblastic clustering, and dyserythropoietic signs in normal BM. We identified CD45(dim) Gly-A(dim) CD71(bright) cells (red blood cell precursors at different maturation stage) as the target of the antibodies. Erythropoietin (EPO) levels were reduced and EPO receptors (EPO-R) increased in BM culture supernatants from positive patients. However, flow cytometric analysis showed that neither EPO nor EPO-R was involved in an abnormal stimulation driven by these autoantibodies. Values of the proapoptotic protein Bax were increased in positive patients and Bcl-2 levels were decreased, although not significantly.
MDS patients with anti-erythroblast autoimmunity showed increased BM apoptosis, suggesting that the autoimmune reaction may contribute to an unfavorable BM microenvironment for optimal erythropoiesis.
低危骨髓增生异常综合征（MDS）表现出多种免疫异常，包括自身免疫表现和/或明显自身免疫性疾病的频率增加，其预后意义仍存在争议。
我们研究了70例早期MDS（难治性贫血和伴有环形铁粒幼细胞的难治性贫血）患者有丝分裂原刺激的骨髓（BM）培养物中是否存在成红细胞抗体。
66%的患者显示成红细胞抗体阳性，同时伴有BM红系增生和外周血溶血表现。阳性培养物的上清液可诱导正常BM中总体细胞数量增加、成红细胞聚集出现以及红系造血异常体征。我们将CD45（dim）Gly-A（dim）CD71（bright）细胞（不同成熟阶段的红细胞前体）确定为抗体的靶标。阳性患者的BM培养上清液中促红细胞生成素（EPO）水平降低而EPO受体（EPO-R）增加。然而，流式细胞术分析表明，EPO和EPO-R均未参与这些自身抗体驱动的异常刺激。阳性患者中促凋亡蛋白Bax的值升高，Bcl-2水平降低，尽管降低不显著。
具有抗成红细胞自身免疫的MDS患者显示BM凋亡增加，提示自身免疫反应可能导致不利于最佳红细胞生成的BM微环境。
