目的:了解骨髓增生异常综合征(myelodysplastic syndromes,MDS)患者骨髓中巨噬细胞所占比例,并分析其与Th细胞、IPSS积分及骨髓CD34+细胞比例间的相关性。方法:以CD14、CD68标记巨噬细胞,以CD3、CD8、干扰素γ(interferon γ, IFN-γ)、白细胞介素(interlukin, IL-4)标记T细胞,采用流式细胞术检测47例MDS患者骨髓中的巨噬细胞百分比以及Th细胞活化情况,另设8名志愿者为对照组。结果:①低危MDS患者骨髓中的巨噬细胞百分比为1.56%±0.22%,显著高于高危MDS患者(0.20%±0.07%) (P<0.001)及正常对照者(0.62%±0.09%)(P<0.001)。②MDS患者骨髓中的巨噬细胞百分比与Th1细胞百分比呈正相关(r=0.434, P<0.01)。③MDS患者骨髓中巨噬细胞百分比与国际预后积分系统(international prognostic scoring system, IPSS)呈负相关(r=-0.532, P<0.001),同时也与骨髓原始细胞百分比呈负相关(r=-0.457, P<0.01),与外周血血红蛋白浓度成负相关(r=-0.398, P<0.01),与骨髓CD34+细胞百分比呈负相关(r=-0.324, P<0.05)。结论:低危MDS患者骨髓中巨噬细胞增加,并可能导致了Th1细胞的异常激活;检测MDS患者骨髓中巨噬细胞百分比可能有助于判断其预后。
Objective: To investigate the percentage of bone marrow macrophages and its correlations with IPSS (international prognostic scoring system) score and percentage of bone marrow CD34+ cells in patients with myelodysplastic syndromes (MDS). Methods: The percentages of bone marrow macrophages were detected by flow cytometry using CD14 and CD68 labeling and the activation of Th cells was detected by flow cytometry using CD3, CD8, IFN-γ, IL-4 labeling. Results: ① Low-risk MDS demonstrated increased percentage of macrophages (1.56%±0.22%) in bone marrow compared to patients with high-risk MDS (0.20%±0.07%) (P<0.001) and controls (0.62%±0.09%) (P<0.001). ② The percentage of bone marrow macrophages was correlated positively with the proportion of Th1 cells (r=0.434, P<0.01). ③ The percentage of bone marrow macrophages was correlated negatively with IPSS score (r=-0.532, P<0.001), percentage of bone marrow myeloblast cells (r=-0.457, P<0.01), peripheral blood hemoglobin concentration (r=-0.398, P<0.01) and percentage of bone marrow CD34+ cells (r=-0.324, P<0.05). Conclusions: The increased percentage of bone marrow macrophages may contribute to the abnormal activation of Th1 cells in low-risk MDS. Detecting the percentage of macrophage may be helpful in evaluating the prognosis of MDS.
[1] Glenthøj A, Ørskov AD, Hansen JW, et al. Immune Mechanisms in Myelodysplastic Syndrome[J]. Int J Mol Sci,2016,17(6),pii:E944.
[2] Gañán-Gómez I, Wei Y, Starczynowski DT, et al.Deregu-lation of innate immune and inflammatory signaling in myelodysplastic syndromes[J]. Leukemia,2015,29(7):1458-1469.
[3] 李晓, 应韶旭, 刘薏芝, 等. 骨髓增生异常综合征巨噬细胞增生与造血细胞凋亡的相关性[J]. 中华病理学杂志,2003,32(3):226-229.
[4] Kitagawa M, Kamiyama R, Kasuga T.Increase in number of bone marrow macrophages in patients with myelodysplastic syndromes[J]. Eur J Haematol,1993,51(1):56-58.
[5] 吴凌云, 李晓, 常春康, 等. 骨髓增生异常综合征患者T细胞异常极化导致的负性造血调控[J]. 中华血液学杂志,2007,28(8):549-554.
[6] Allavena P, Sica A, Garlanda C, et al.The Yin-Yang of tumor-associated macrophages in neoplastic progression and immune surveillance[J]. Immunol Rev,2008,222:155-161.
[7] Mantovani A, Sozzani S, Locati M, et al.Macrophage polarization: tumor-associated macrophages as a paradigm for polarized M2 mononuclear phagocytes[J]. Trends Immunol,2002,23(11):549-555.
[8] Komohara Y, Hasita H, Ohnishi K, et al.Macrophage infiltration and its prognostic relevance in clear cell renal cell carcinoma[J]. Cancer Sci,2011,102(7):1424-1431.
[9] Kamper P, Bendix K, Hamilton-Dutoit S, et al.Tumor-infiltrating macrophages correlate with adverse prognosis and Epstein-Barr virus status in classical Hodgkin's lymphoma[J]. Haematologica,2011,96(2):269-276.
[10] Itoh M, Yago K, Shimada H, et al.Reversible acceleration of disease progression following cyclosporin A treatment in a patient with myelodysplastic syndrome[J]. Int J Hematol,2002,75(3):302-304.
[11] Ohmori S, Ohmori M, Yamagishi M, et al.MDS-macrophage derived inhibitory activity on myelopoiesis of MDS abnormal clones[J]. Br J Haematol,1993,83(3):388-391.
[12] Hom J, Dulmovits BM, Mohandas N, et al.The erythroblastic island as an emerging paradigm in the anemia of inflammation[J]. Immunol Res,2015,63(1-3):75-89.
[13] Reza S, Dar S, Andric T, et al.Biologic characteristics of 164 patients with myelodysplastic syndromes[J]. Leuk Lymphoma,1999,33(3-4):281-287.
[14] Motomura S, Motoji T, Okutomi K, et al.Successful treatment of refractory anemia by high-dose methylprednisolone associated with an increment in CD68-positive cells in bone marrow[J]. Am J Hematol,2001,66(2):80-84.