刘丽娟
华北电网有限公司北京电力医院呼吸内科,北京 100073
[摘要] 目的 探讨血清铁蛋白(SF)与β2-微球蛋白(β2-MG)在感染性疾病中浓度的变化以及临床价值。 方法 选择2012年1月~2013年1月期间华北电网有限公司北京电力医院收治的感染性疾病患者60例作为感染组,主要以细菌感染为主,且均有病原学依据。并以干部门诊同期健康体检患者60例作为正常对照组,测定并比较分析两组患者血清SF和β2-MG结果。 结果 感染组患者血清SF水平为(325.85±189.10) μg/L,β2-MG水平为(3.92±2.20) mg/L,均显著高于正常对照组[血清SF水平(130.95±77.40) μg/L,β2-MG水平(2.02±0.59) mg/L],差异有高度统计学意义(P < 0.01)。感染组患者治疗后好转出院54例,住院期间死亡6例,但两组患者的SF、β2-MG水平比较,差异均无统计学意义(P > 0.05)。 结论 SF和β2-MG浓度的测定对感染的早期判定以及抗生素的合理使用方面均具有指导意义。
[关键词] 铁蛋白;β2微球蛋白;感染性疾病;临床价值
[中图分类号] R733.4 [文献标识码] A [文章编号] 1673-7210(2014)03(b)-0038-03
Expression and clinical significance of serum Ferritin and β2-microglobulin in patients with infectious diseases
LIU Lijuan
Department of Respiration, Beijing Electric Power Hospital of North China Grid Limited Company, Beijing 100073, China
[Abstract] Objective To investigate the levels of serum Ferritin (SF) and β2- microglobulin (β2-MG) in patients with infectious diseases. Methods From January 2012 to January 2013 in Beijing Electric Power Hospital of North China Grid Limited Company, 60 patients with infectious diseases were as infection group, which the mainly infection was bacterial infection with etiological basis, and 60 patients from clinic physical examination were as control group. Then, the levels of SF and β2-MG in two groups were measured and compared. Results SF levels of infection group was(325.85±189.10) μg/L, and β2-MG levels was (3.92±2.20) mg/L, both of them were significantly higher than those of control group[SF (130.95±77.40) μg/L,β2-MG (2.02±0.59) mg/L], the differences were statistically significant (P < 0.01). After treatment, 54 cases improved, 6 patients died, but the levels of SF, β2-MG of two groups were compared, the differences were not statistically significant (P > 0.05). Conclusion SF and β2-MG concentration determination is guiding significance to the early infectious decision and the rational using antibiotic.
[Key words] Serum ferritin ; β2-microglobulin (β2-MG); Infectious diseases; Clinical value
血清铁蛋白(SF)和β2-微球蛋白(β2-MG)是人体内重要的肿瘤标志物,在肿瘤以及多种疾病中均具有较高的阳性检出率,可指导疾病的诊断与治疗[1]。近年来,一些研究发现,此两项指标在感染性疾病患者中均有不同程度升高,对感染的早期判定以及抗生素的合理使用方面均具有指导意义[2-5]。因此,本研究对60例感染性疾病患者进行检测,旨在了解SF、β2-MG在感染性疾病患者中的表达及临床意义。
1 资料与方法
1.1 一般资料
选择2012年1月~2013年1月华北电网有限公司北京电力医院(以下简称“我院”)收治的感染性疾病患者60例,主要以细菌感染为主,且均有病原学依据。其中,男31例,女29例;年龄42~90岁,平均(77.48±10.05)岁;痰培养阳性者28例,尿培养阳性者27例,血培养阳性者5例;大肠埃希菌41例,肺炎克雷白杆菌16例,奇异变形杆菌2例,阴沟肠杆菌1例。入选病例均无肿瘤、肾功能不全病史,SF和β2-MG浓度的情况未受其他疾病影响。对照组60例,为干部门诊同期健康体检患者,男34例,女26例,年龄38~88岁,平均(74.25±11.37)岁,均无感染、贫血、心脑血管疾病、恶性肿瘤等疾病。两组性别、年龄比较,差异均无统计学意义(P > 0.05),具有可比性。本研究已经我院伦理委员会通过,所有研究对象均知情同意,并签署了知情同意书。
1.2 检测方法
两组均于清晨空腹采集患者静脉血3 mL,留取上层血清并分装,置于-20℃保存待测。SF和β2-MG均用Diasorin S.P.A公司生产的LIAISON化学发光分析仪测定。
1.3 观察项目
感染组与对照组血清SF和β2-MG浓度的变化;感染组不同转归患者血清SF和β2-MG浓度的变化。
1.4 统计学方法
采用SPSS17.0统计软件对数据进行分析,正态分布计量资料以均数±标准差(x±s)表示,组间比较采用t检验,以P < 0.05为差异有统计学意义。
2 结果
2.1 感染组与对照组血清SF和β2-MG浓度比较
感染组血清SF和β2-MG水平明显高于对照组,两组比较,差异均有高度统计学意义(P < 0.01)。见表1。
表1 感染组与对照组SF和β2微球蛋白浓度比较(x±s)
注:SF:血清铁蛋白;β2-MG:β2-微球蛋白
2.2 感染组不同转归患者血清SF 和β2-MG浓度比较
感染组中住院死亡患者比好转出院患者血清SF和β2-MG水平有所升高,但两组比较,差异均无统计学意义(P > 0.05)。见表2。
表2 感染组不同转归患者血清铁蛋白和β2微球蛋白浓度比较(x±s)
注:SF:血清铁蛋白;β2-MG:β2-微球蛋白
3 讨论
SF是去铁蛋白和铁核心Fe3+形成的复合物,铁蛋白的铁核心Fe3+具有强大的结合铁和贮备铁的能力,以维持体内铁的供应和血红蛋白相对稳定性。SF是铁的主要贮存形式,分布于全身各组织,但以肝、脾、骨髓含量最多,其含量变化可作为判断是否缺铁或铁负荷过量的指标。在感染性疾病过程中存在铁平衡的紊乱,而铁蛋白作为一种急性期蛋白(acute phase protein,APP),是由感染患者炎症部位的巨噬细胞和中性粒细胞所分泌TNF-α、IL-1和IL-6诱导肝细胞合成与分泌的[6]。Kossiva等[7]在2012年发表的一个单中心研究显示3F和铁调素(Hepcidin)水平在急性发热患者中明显升高,且SF与铁的比值(ferritinto iron ratio,FIR)能够作为细菌感染的辅助性诊断指标。Huang等[5]的研究数据也证明细菌感染患者SF水平明显升高。近年来一些国外文献报道SF水平在布鲁菌病和军团菌肺炎中均显著升高[8-9],并认为SF可作为一项辅助诊断指标指导临床工作。本研究结果提示感染组患者SF浓度较对照组明显升高,且统计学差异十分显著(P < 0.01),这与以上国外研究相符,因此,本研究认为感染者体内急性期反应时炎症相关细胞因子增多,从而使肝细胞合成和分泌SF增多。此外,有学者研究了42例流行性出血热患者,证实了SF升高的水平与疾病的严重程度呈正相关,且对预后的评估具有较高的灵敏性和特异性[10]。本研究中,感染组死亡患者SF均有升高,但与好转出院患者比较无明显统计学意义(P > 0.05),这有待于进一步的临床大样本研究。
β2-MG是一种由淋巴细胞、血小板、多形核白细胞产生的一种小分子球蛋白,分子质量为11 800,它是细胞表面人类淋巴细胞抗原(HLA)的β链(轻链)部分(为一条单链多肽),广泛存在于淋巴细胞表面及白细胞、血小板、上皮细胞和间叶细胞的膜上,当组织相容抗原代谢与降解或细胞更新时,以游离形式释放到体液中[11]。正常人β2-MG的合成率以及从细胞膜上的释放量相当恒定[1],但是,当机体出现炎性反应、免疫应激、细胞变性坏死以及肿瘤细胞异常代谢等情况时,其合成与释放增多。在感染性疾病过程中,由于炎症的刺激,细胞活动旺盛,免疫活性介质使淋巴细胞转化,在激活补体的同时使炎症加剧,造成高细胞因子血症,使β2-MG合成、释放增加,从而血清浓度升高[12]。D'Souza等[13]的研究发现,β2-MG分子基因中断的小鼠容易感染结核杆菌,这可能与β2-MG分子基因能够早期有效地促进保护性淋巴细胞进入感染灶进行防御有关。同时Soderblom等[14]也发现局部的细胞免疫事件能够解释类风湿性关节炎以及结核性胸膜炎患者胸水中β2-MG浓度升高的原因。因此,认为血清β2-MG浓度增高很可能为机体的一种防御性反应,其基因表达的缺失增加疾病的易感性。本研究结果提示感染组患者β2-MG浓度明显高于对照组,差异有高度统计学意义(P < 0.01),这与国内外研究[15-17]是一致的,说明感染组患者机体处于一种防御反应阶段,这可作为感染性疾病的一项辅助性诊断指标,为疾病的早期诊断与治疗提供可靠依据。目前,国外β2-MG水平升高在结核病、中枢神经系统感染中报道较多[13,16,18],在肺炎支原体肺炎、肺炎克雷白杆菌菌血症也偶有报道[19-20]。本研究主要针对病原学阳性的细菌感染,且以老年人为主,结果显示此类患者血清中β2-MG明显升高,虽然与其预后无明显相关性,但对临床诊断与治疗仍有很大帮助。
综上所述,SF和β2-MG是感染性疾病时机体炎性反应的产物,参与了疾病的发生、发展过程,通过国内外研究以及本实验结果得出,二者升高均可作为感染的辅助诊断指标,因此,在对感染的早期判定以及抗生素的合理使用方面均具有指导意义。
[参考文献]
[1] 王自正.现代医学标记免疫学[M].北京:人民军医出版社,2000:58,66-211.
[2] 黄刘炜,管丽华,雷后兴,等.肺炎患儿血清糖蛋白及β2微球蛋白的含量变化及意义[J].中国全科医学,2003,10(6):822.
[3] 龙宪和.血清铁蛋白高值对急性炎症感染性疾病的诊断临床应用探讨[J].标记免疫分析与临床,2001,8(4):242-244.
[4] Wanchu A,Arora S,Bhatnagar A,et al. Decline in beta-2 microglobulin levels after antitubercular therapy in tubercular patients with HIV infection [J]. Indian J Chest Dis Allied Sci,2001,43(4):211-215.
[5] Huang HH,Yan HC,Han CL,et al. Association of in vitro oxidative stress,serum ferritin concentration and C-reactive protein in febrile emergency room patients [J]. Clin Invest Med,2005,28(2):48-54.
[6] Marino IR,Panarelio G,Singh N. Efficacy of Aspergillusgalactomannan directed preemptive therapy for the prevention of invasive aspergillosis in organ transplant recipients [J]. Transpl Infect Dis ,2002,4(4):226-227.
[7] Kossiva L,Gourgiotis DI,Tsentidis C,et al. Serum hepcidin and ferritin to iron ratio in evaluation of bacterial versus viral infections in children:a single-center study [J]. Pediatr Infect Dis J,2012,31(8):795-798.
[8] Arica V,Silfeleri,Arica S,et al. Brucellosis with very high ferritin levels:report of five cases [J]. Hum Exp Toxicol,2012,31(1):104-106.
[9] Karabay O,Tuna N,Ogutlu A,et al. High ferritin and myoglobin level in legionella pneumonia:a case report and review of literature [J]. Indian J Pathol Microbiol,2011,54(2):381-383.
[10] Barut S,Dincer F,Sahin I. Increased serum ferritin level in patients with Crimean-Congo hemorrhagic fever:can it be a new severity criterion? [J]. Int J Infect Dis,2010,14(1):50-54.
[11] 郎江明.临床免疫诊断学[M].广州:广东科技出版社,2003:483.
[12] 胡红兵,夏维,刘芳,等.肺炎患儿血清β2-MG及白细胞介质-2水平变化[J].中国当代儿科杂志,2001,3(5):549-550.
[13] D'Souza CD,Cooper AM,Frank AA,et al. A novel nonclassic beta2-microglobulin-restricted mechanism influencing early lymphocyte accumulation and subsequent resistance to tuberculosis in the lung [J]. Am J Respir Cell Mol Biol,2000,23(2):188-193.
[14] Soderblom T,Nyberg P,Pettersson T,et al. Pleural fluid beta-2-microglobulin and angiotensin-converting enzyme concentrations in rheumatoid arthritis and tuberculosis [J]. Respiration,1996,63(5):272-276.
[15] 蒋荷萍.脑脊液乳酸、β2-微球蛋白、C反应蛋白和酶活性测定在脑膜炎中的应用[J].检验医学,2012,27(7):609-611.
[16] Wanchu A,Arora S,Bhatnagar A,et al. Decline in beta-2 microglobulin levels after antitubercular therapy in tubercular patients with HIV infection[J]. Indian J Chest Dis Allied Sci,2001,43(4):211-215.
[17] 陈品儒,陈华,易小萍,等.血清β2-微球蛋白的测定在菌阳肺结核诊断价值方面的探讨[J].临床肺科杂志,2007,12(8):868-869.
[18] Takahashi S,Oki J,Miyamoto A,et al. Beta-2-microglobulin and ferritin in cerebrospinal fluid for evaluation of patients with meningitis of different etiologies [J]. Brain Dev,1999,21(3):192-199.
[19] Inamo Y,Ishizuka Y,Hashimoto K,et al. A 7-year-old girl with subcutaneous emphysema,pneumomediastinum,pneumothorax,andpneumoretroperitoneum caused by Mycoplasma pneumoniae pneumonia [J]. J Infect Chemother,2012,18(2):247-250.
[20] Cogen AL,Moore TA. Beta2-microglobulin-dependent bacterial clearance and survival during murine Klebsiella pneumoniae bacteremia [J]. Infect Immun,2009,77(1):360-366.
(收稿日期:2013-10-28 本文编辑:苏 畅)
[5] Huang HH,Yan HC,Han CL,et al. Association of in vitro oxidative stress,serum ferritin concentration and C-reactive protein in febrile emergency room patients [J]. Clin Invest Med,2005,28(2):48-54.
[6] Marino IR,Panarelio G,Singh N. Efficacy of Aspergillusgalactomannan directed preemptive therapy for the prevention of invasive aspergillosis in organ transplant recipients [J]. Transpl Infect Dis ,2002,4(4):226-227.
[7] Kossiva L,Gourgiotis DI,Tsentidis C,et al. Serum hepcidin and ferritin to iron ratio in evaluation of bacterial versus viral infections in children:a single-center study [J]. Pediatr Infect Dis J,2012,31(8):795-798.
[8] Arica V,Silfeleri,Arica S,et al. Brucellosis with very high ferritin levels:report of five cases [J]. Hum Exp Toxicol,2012,31(1):104-106.
[9] Karabay O,Tuna N,Ogutlu A,et al. High ferritin and myoglobin level in legionella pneumonia:a case report and review of literature [J]. Indian J Pathol Microbiol,2011,54(2):381-383.
[10] Barut S,Dincer F,Sahin I. Increased serum ferritin level in patients with Crimean-Congo hemorrhagic fever:can it be a new severity criterion? [J]. Int J Infect Dis,2010,14(1):50-54.
[11] 郎江明.临床免疫诊断学[M].广州:广东科技出版社,2003:483.
[12] 胡红兵,夏维,刘芳,等.肺炎患儿血清β2-MG及白细胞介质-2水平变化[J].中国当代儿科杂志,2001,3(5):549-550.
[13] D'Souza CD,Cooper AM,Frank AA,et al. A novel nonclassic beta2-microglobulin-restricted mechanism influencing early lymphocyte accumulation and subsequent resistance to tuberculosis in the lung [J]. Am J Respir Cell Mol Biol,2000,23(2):188-193.
[14] Soderblom T,Nyberg P,Pettersson T,et al. Pleural fluid beta-2-microglobulin and angiotensin-converting enzyme concentrations in rheumatoid arthritis and tuberculosis [J]. Respiration,1996,63(5):272-276.
[15] 蒋荷萍.脑脊液乳酸、β2-微球蛋白、C反应蛋白和酶活性测定在脑膜炎中的应用[J].检验医学,2012,27(7):609-611.
[16] Wanchu A,Arora S,Bhatnagar A,et al. Decline in beta-2 microglobulin levels after antitubercular therapy in tubercular patients with HIV infection[J]. Indian J Chest Dis Allied Sci,2001,43(4):211-215.
[17] 陈品儒,陈华,易小萍,等.血清β2-微球蛋白的测定在菌阳肺结核诊断价值方面的探讨[J].临床肺科杂志,2007,12(8):868-869.
[18] Takahashi S,Oki J,Miyamoto A,et al. Beta-2-microglobulin and ferritin in cerebrospinal fluid for evaluation of patients with meningitis of different etiologies [J]. Brain Dev,1999,21(3):192-199.
[19] Inamo Y,Ishizuka Y,Hashimoto K,et al. A 7-year-old girl with subcutaneous emphysema,pneumomediastinum,pneumothorax,andpneumoretroperitoneum caused by Mycoplasma pneumoniae pneumonia [J]. J Infect Chemother,2012,18(2):247-250.
[20] Cogen AL,Moore TA. Beta2-microglobulin-dependent bacterial clearance and survival during murine Klebsiella pneumoniae bacteremia [J]. Infect Immun,2009,77(1):360-366.
(收稿日期:2013-10-28 本文编辑:苏 畅)
[5] Huang HH,Yan HC,Han CL,et al. Association of in vitro oxidative stress,serum ferritin concentration and C-reactive protein in febrile emergency room patients [J]. Clin Invest Med,2005,28(2):48-54.
[6] Marino IR,Panarelio G,Singh N. Efficacy of Aspergillusgalactomannan directed preemptive therapy for the prevention of invasive aspergillosis in organ transplant recipients [J]. Transpl Infect Dis ,2002,4(4):226-227.
[7] Kossiva L,Gourgiotis DI,Tsentidis C,et al. Serum hepcidin and ferritin to iron ratio in evaluation of bacterial versus viral infections in children:a single-center study [J]. Pediatr Infect Dis J,2012,31(8):795-798.
[8] Arica V,Silfeleri,Arica S,et al. Brucellosis with very high ferritin levels:report of five cases [J]. Hum Exp Toxicol,2012,31(1):104-106.
[9] Karabay O,Tuna N,Ogutlu A,et al. High ferritin and myoglobin level in legionella pneumonia:a case report and review of literature [J]. Indian J Pathol Microbiol,2011,54(2):381-383.
[10] Barut S,Dincer F,Sahin I. Increased serum ferritin level in patients with Crimean-Congo hemorrhagic fever:can it be a new severity criterion? [J]. Int J Infect Dis,2010,14(1):50-54.
[11] 郎江明.临床免疫诊断学[M].广州:广东科技出版社,2003:483.
[12] 胡红兵,夏维,刘芳,等.肺炎患儿血清β2-MG及白细胞介质-2水平变化[J].中国当代儿科杂志,2001,3(5):549-550.
[13] D'Souza CD,Cooper AM,Frank AA,et al. A novel nonclassic beta2-microglobulin-restricted mechanism influencing early lymphocyte accumulation and subsequent resistance to tuberculosis in the lung [J]. Am J Respir Cell Mol Biol,2000,23(2):188-193.
[14] Soderblom T,Nyberg P,Pettersson T,et al. Pleural fluid beta-2-microglobulin and angiotensin-converting enzyme concentrations in rheumatoid arthritis and tuberculosis [J]. Respiration,1996,63(5):272-276.
[15] 蒋荷萍.脑脊液乳酸、β2-微球蛋白、C反应蛋白和酶活性测定在脑膜炎中的应用[J].检验医学,2012,27(7):609-611.
[16] Wanchu A,Arora S,Bhatnagar A,et al. Decline in beta-2 microglobulin levels after antitubercular therapy in tubercular patients with HIV infection[J]. Indian J Chest Dis Allied Sci,2001,43(4):211-215.
[17] 陈品儒,陈华,易小萍,等.血清β2-微球蛋白的测定在菌阳肺结核诊断价值方面的探讨[J].临床肺科杂志,2007,12(8):868-869.
[18] Takahashi S,Oki J,Miyamoto A,et al. Beta-2-microglobulin and ferritin in cerebrospinal fluid for evaluation of patients with meningitis of different etiologies [J]. Brain Dev,1999,21(3):192-199.
[19] Inamo Y,Ishizuka Y,Hashimoto K,et al. A 7-year-old girl with subcutaneous emphysema,pneumomediastinum,pneumothorax,andpneumoretroperitoneum caused by Mycoplasma pneumoniae pneumonia [J]. J Infect Chemother,2012,18(2):247-250.
[20] Cogen AL,Moore TA. Beta2-microglobulin-dependent bacterial clearance and survival during murine Klebsiella pneumoniae bacteremia [J]. Infect Immun,2009,77(1):360-366.
(收稿日期:2013-10-28 本文编辑:苏 畅)