Profiles of interferon-gamma and interleukin-2 in patients after allogeneic hematopoietic stem cell transplantation.

Malwina Rybicka-Ramos, Mirosław Markiewicz, Aleksandra Suszka-Świtek, Ryszard Wiaderkiewicz, Sylwia Mizia, Monika Dzierżak-Mietła, Krzysztof Białas
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Abstract

Background: Allogeneic hematopoietic stem cell transplantation (allo-HSCT) may be related to the occurrence of complications, including graft-versus-host disease (GvHD) and infections. The pathogenesis of acute GvHD is connected with T lymphocytes, which identify alloantigens on host's antigen-presenting cells, activate production of interferon-gamma (IFN-gamma) and interleukin-2 (IL-2), and act on the immune effector cells and damage tissues and organs.

Aim: The aim of the study was to investigate and distinguish serum concentration profiles of IFN-gamma and IL-2 within a 30-d period after allo-HSCT.

Methods: We enrolled 62 patients, i.e., 30 (48%) male and 32 (52%) female subjects [median age 49.5 (19-68) years], after allo-HSCT from siblings (n = 12) or unrelated donors (n = 50) due to acute myeloid leukemia with myeloablative conditioning (n = 26; 42%) and with non-myeloablative conditioning (n = 36; 58%). All patients were given standard immunosuppressive therapy with cyclosporin-A and methotrexate and pre-transplant antithymocyte globulin in the unrelated setting. Blood samples were collected pre-transplant before and after (on day -1) the conditioning therapy and on days +2,+4, +6, +10, +20, and +30 after allo-HSCT. Serum levels of IL-2 and IFN-gamma were determined using ELISA.

Results: Patients were divided into four groups depending on the presence of acute GvHD and clinical manifestations of infection. Group I included patients with neither acute GvHD nor infections [n = 15 (24%)], group II consisted of patients with infections without acute GvHD [n = 17 (27%)], group III was comprised of patients with acute GvHD without infections [n = 9 (15%)], and group IV included patients with both acute GvHD and infections [n = 21 (34%)]. IFN-gamma concentrations were higher in Group II than in other groups on days +20 (P = 0.014) and +30 (P = 0.008). Post-hoc tests showed lower concentrations of IFN-gamma on day +30 in groups I (P = 0.039) and IV (P = 0.017) compared to group II. The levels of IL-2 were mostly undetectable.

Conclusion: Serum levels of IFN-gamma following allo-HSCT progressively escalate. High serum levels of IFN-gamma are related to infectious complications rather than acute GvHD. Serum concentrations of IL-2 in most patients are undetectable.

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异基因造血干细胞移植后患者干扰素- γ和白细胞介素-2的变化。
背景:同种异体造血干细胞移植(alloo - hsct)可能与移植物抗宿主病(GvHD)和感染等并发症的发生有关。急性GvHD的发病机制与T淋巴细胞有关,T淋巴细胞识别宿主抗原呈递细胞上的异体抗原,激活干扰素- γ (ifn - γ)和白细胞介素-2 (IL-2)的产生,作用于免疫效应细胞,损伤组织器官。目的:本研究的目的是研究和区分同种异体造血干细胞移植后30天内血清中ifn - γ和IL-2的浓度谱。方法:我们招募了62例患者,即30例(48%)男性和32例(52%)女性受试者[中位年龄49.5(19-68)岁],由于急性骨髓性白血病伴有清髓条件(n = 26),他们接受了来自兄弟姐妹(n = 12)或非亲属供体(n = 50)的同种异体造血干细胞移植(n = 26);42%)和非清髓调节组(n = 36;58%)。所有患者均给予环孢素a和甲氨蝶呤的标准免疫抑制治疗,并在移植前注射抗胸腺细胞球蛋白。在调理治疗前后(第1天)以及同种异体造血干细胞移植后+2、+4、+6、+10、+20和+30天采集移植前血液样本。ELISA法检测血清IL-2、ifn - γ水平。结果:根据急性GvHD的存在和感染的临床表现将患者分为四组。I组为无急性GvHD和感染的患者[n = 15 (24%)], II组为无急性GvHD感染的患者[n = 17 (27%)], III组为无感染的急性GvHD患者[n = 9 (15%)], IV组为既有急性GvHD又有感染的患者[n = 21(34%)]。第20天(P = 0.014)和第30天(P = 0.008), II组ifn - γ浓度高于其他组。事后测试显示,与II组相比,I组(P = 0.039)和IV组(P = 0.017)在第30天的ifn - γ浓度较低。IL-2的水平大多检测不到。结论:同种异体造血干细胞移植后血清ifn - γ水平逐渐升高。血清中ifn - γ的高水平与感染性并发症有关,而与急性GvHD无关。大多数患者的血清IL-2浓度无法检测到。
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