中国经典型多发性硬化患者β干扰素-1b治疗前后血清尿酸水平

徐雁, 刘彩燕, 张遥, 孔令燕, 冯逢, 金征宇, 崔丽英

徐雁, 刘彩燕, 张遥, 孔令燕, 冯逢, 金征宇, 崔丽英. 中国经典型多发性硬化患者β干扰素-1b治疗前后血清尿酸水平[J]. 协和医学杂志, 2012, 3(3): 282-286. DOI: 10.3969/j.issn.1674-9081.2012.03.008
引用本文: 徐雁, 刘彩燕, 张遥, 孔令燕, 冯逢, 金征宇, 崔丽英. 中国经典型多发性硬化患者β干扰素-1b治疗前后血清尿酸水平[J]. 协和医学杂志, 2012, 3(3): 282-286. DOI: 10.3969/j.issn.1674-9081.2012.03.008
Yan XU, Cai-yan LIU, Yao ZHANG, Ling-yan KONG, Feng FENG, Zheng-yu JIN, Li-ying CUI. Serum Uric Acid Levels in Chinese Patients with Classic Multiple Sclerosis: Before and After Treatment with Interferon-beta 1b[J]. Medical Journal of Peking Union Medical College Hospital, 2012, 3(3): 282-286. DOI: 10.3969/j.issn.1674-9081.2012.03.008
Citation: Yan XU, Cai-yan LIU, Yao ZHANG, Ling-yan KONG, Feng FENG, Zheng-yu JIN, Li-ying CUI. Serum Uric Acid Levels in Chinese Patients with Classic Multiple Sclerosis: Before and After Treatment with Interferon-beta 1b[J]. Medical Journal of Peking Union Medical College Hospital, 2012, 3(3): 282-286. DOI: 10.3969/j.issn.1674-9081.2012.03.008

中国经典型多发性硬化患者β干扰素-1b治疗前后血清尿酸水平

详细信息
    通讯作者:

    崔丽英 电话:010-69156373, E-mail:pumchcly@yahoo.com.cn

  • 中图分类号: R741

Serum Uric Acid Levels in Chinese Patients with Classic Multiple Sclerosis: Before and After Treatment with Interferon-beta 1b

More Information
  • 摘要:
      目的  探讨中国经典型多发性硬化(classical multiple sclerosis, CMS)患者β干扰素-1b治疗前后血清尿酸(uric acid, UA)水平的变化及其与复发率、扩展残疾状态评分(Expanded Disability Status Scale, EDSS)和颅内增强病灶(contrast-enhancing lesions, CELs)数目间的关系。
      方法  12例CMS患者(10例女性, 2例男性, 年龄:24~54岁)被纳入至一项为期6个月的疗效观察研究。在疾病缓解期, 给予β干扰素-1b(250 μg, 皮下注射, 隔日1次)治疗。治疗前后评估患者EDSS评分、年复发次数、颅内CELs数目和血清UA水平。
      结果  治疗后, 患者年复发次数(0.0比0.9, P=0.011)和颅内CELs数目(0.0比1.5, P=0.007)较治疗前明显减低; EDSS评分有降低趋势(2.0比2.8), 但差异无统计学意义(P=0.064);血清UA水平从222.2 μmol/L升高至234.9 μmol/L, 但差异亦无统计学意义(P=0.213)。进一步研究发现, 血清UA水平升高与颅内CELs数目减低显著相关(r=-0.716, P=0.009)。
      结论  血清UA水平有可能成为评估CMS患者对β干扰素-1b治疗反应的一个监测指标。
    Abstract:
      Objective  To investigate the changes of serum uric acid (UA) level and its relationship with relapse rate, Expanded Disability Status Scale (EDSS) score, and the number of contrast-enhancing lesions (CELs) in Chinese patients with classic multiple sclerosis (CMS) before and after interferon (IFN) -beta 1b treatment.
      Methods  Twelve patients (10 women and 2 men, aged 24 to 54 years) with definite CMS were enrolled into a 6-month open-label observational treatment study. IFN-beta 1b (250 μg, qod) was injected subcutaneously during remission stage. EDSS, relapse rate, number of CELs, and serum UA levels were examined both at baseline and at the end of the study.
      Results  After treatment, the median relapse rate (0.0 vs. 0.9, P=0.011) and median number of CELs (0.0 vs. 1.5, P=0.007) decreased significantly compared with those before treatment. The median EDSS score also decreased from 2.8 to 2.0, but the difference was not statistically significant (P=0.064). Serum UA level increased from 222.2 μmol/L to 239.4 μmol/L after treatment, although the difference was not statistically significant (P=0.213). However, there was significant correlation between the increase in UA level and the decrease in number of CELs (r=-0.716, P=0.009).
      Conclusions  UA may serve as an easily detectable and economic marker for the blood-brain barrier function in CMS patients and for the responses to IFN-beta 1b treatment.
  • 大疱性类天疱疮(bullous pemphigoid,BP)是一种严重的自身免疫性大疱性疾病,BP患者血清中出现抗BP180和BP230的IgG型自身抗体,可与皮肤基底膜结合而诱发水疱形成。近年来,一种新的抗体类型IgE逐渐进入人们的视野。IgE在过敏性疾病、系统性红斑狼疮和类风湿性关节炎等自身免疫性疾病中均发挥重要作用。早在1974年就有学者提出天疱疮和类天疱疮患者血清中IgE升高,且皮损基底膜带可见IgE沉积[1]。然而,该现象一直未引起足够重视,直到1984年,有学者提出BP患者血清中IgE水平与病情相关[2]。但随着近年来对BP180 IgE和BP230 IgE研究的逐渐深入,该结论受到质疑。国外有报道显示血清中总IgE水平与病情关系不明显[3-4],目前国内尚缺乏相关数据。为此,本研究对1990年1月至2011年8月在本院住院的具有完整临床资料的BP患者进行回顾性分析,同时对2011年8月至2012年4月门诊就诊的BP患者进行前瞻性研究,旨在探讨BP患者外周血总IgE在疾病发生发展过程中的变化特点及与病情的相关性。

    收集1990年1月至2011年8月北京协和医院皮肤科住院BP患者及2011年8月至2012年4月门诊BP患者共223例,所有患者经临床、组织病理、直接和间接免疫荧光(indirect immunofluorescence,IIF)检查证实,均满足BP的诊断标准。选取其中有总IgE检测记录的患者59例作为研究组,其中男33例、女26例,男:女为1. 27 : 1;年龄22 ~ 93岁,平均(65. 3 ± 16. 1)岁; 病程10 d至10年; 59例中,有39例同时进行了IIF检测。所有患者病程中均无哮喘、特应性皮炎、嗜酸性粒细胞(eosinophil,EOS)增多症和高IgE综合征病史。选取30名体检正常的年龄、性别匹配的健康人群作为正常对照组,其中男16例、女14例,平均年龄(62. 8 ± 6. 5)岁。两组在性别、年龄构成上差异无统计学意义(P>0. 05)。

    所有患者根据病程记录,确定病情的严重程度,记录患者不同治疗时期的EOS总数、总IgE水平、皮质类固醇激素(以下简称激素)应用的最大剂量及IIF滴度。总IgE检测方法采用ELISA法。本文所涉及到的激素剂量均换算为泼尼松的剂量,换算方法为: 5 mg泼尼松(泼尼松龙) ≈20 mg氢化可的松≈4 mg曲安西龙(甲泼尼龙,甲强龙) ≈0. 75 mg地塞米松≈0. 8 mg倍他米松。

    数据以M (QL,QU)表示,数据为非正态分布且存在非精确测量值,因此组间比较采用秩和检验,IgE与激素应用最大剂量、EOS数量、IIF滴度间的相关性检验采用Spearman等级相关分析,P<0. 05为差异具有统计学意义。

    59例BP患者中,53例(89. 83%)总IgE升高,其中位数为712. 00 (178. 00,2500. 00) kU/L; 30名正常对照者中,3名(10%)总IgE升高,其中位数为58. 20 (31. 78,68. 50) kU/L。两组间比较差异有统计学意义(Z = - 6. 232,P<0. 001)。

    59例BP患者中,19例有治疗前后IgE的记录,其中14例(73. 68%)患者治疗后IgE下降,但仅有2例(10. 53%)患者降至正常; 4例(21. 05%)患者治疗后轻度升高; 1例(5. 26%)患者病情复发,IgE升高(表 1)。对所有患者治疗前后总IgE进行比较,发现治疗前后体内IgE含量明显变化(Z = - 2. 374,P = 0. 018)。

    表  1  19例大疱性类天疱疮患者治疗前后总IgE的变化
    病例 治疗前(kU/L) 治疗后(kU/L)
    1 117 37. 4
    2 4633 4789
    3 1330 1540
    4 2312 4138*
    5 655 138
    6 >5000 3699
    7 >5000 4423
    8 >5000 3028
    9 4804 1664
    10 6. 9 9
    11 84. 3 28. 2
    12 197 128
    13 3902 375
    14 970 344
    15 150 135
    16 26 41. 3
    17 >5000 3495
    18 2911 898
    19 712 657
    *该患者病情复发时的数据
    下载: 导出CSV 
    | 显示表格

    选择1例有详细记录的BP患者,对其IgE水平与新发水疱数量间的关系进行分析,结果显示患者IgE水平与新发水疱数量的变化趋势大致相同,但IgE水平变化晚于水疱数量变化,且在患者病情控制(无新发水疱)后,IgE水平呈缓慢下降趋势但未降至正常(图 1)。

    图  1  大疱性类天疱疮患者总IgE水平与新发水疱数量间的关系

    59例BP患者中,33例男性患者和26例女性患者的IgE中位数分别为1006. 00 (310. 00,2705. 50) kU/L和496 (144. 75,1575. 50) kU/L,两组间差异无统计学意义(Z = - 1. 191,P = 0. 234)。

    对59例患者的激素应用最大剂量与总IgE水平进行Spearman等级相关分析,结果显示两者间无相关性(r = 0. 040,P = 0. 765)。

    对IgE水平与EOS数量进行Spearman相关分析,结果显示两者间无相关性(r = 0. 203,P = 0. 123)。

    对39例患者总IgE与IIF滴度进行Spearman等级相关分析,结果显示两者间无相关性(r = 0. 161,P = 0. 328)。

    虽然已有大量证据表明抗BP180 IgG抗体与BP发病相关,且与病情相平行[5-6],但越来越多的证据显示IgE水平在BP发病过程中起重要作用:在大多数BP患者血清中可检测到IgE抗体,且沿基底膜带呈线状沉积[7],这些抗体同样结合于BP180 NC16A[8]; 体外实验证明IgE抗体与BP发病相关[9]; 用抗IgE人源化抗体成功治疗1例皮质类固醇治疗无效的BP患者,该抗体能抑制IgE与其相应受体结合[10]。种种迹象表明IgE抗体在BP发病中起重要作用,但IgE水平是否与病情严重程度相关,至今仍无定论。

    BP患者中出现高IgE已是不争的事实。由于所采用方法不同及病例选择不同,测得的IgE升高率也不尽相同。据报道70% ~ 90%的BP患者出现高IgE[3, 11],77%的患者可检测到抗BP180 NC16A IgE抗体[12]。本组资料中高IgE占BP患者的89. 83%,与国外报道的数据相似。高IgE多出现于变态反应性疾病、寄生虫感染等。BP患者出现高IgE,也从一个侧面解释了临床所观测到的BP发病早期出现湿疹皮炎样皮损的原因,提示变态反应可能是BP发病的始动环节。

    为了评价总IgE水平与BP病情的相关性,本研究对所有患者的总IgE水平和激素应用的最大剂量、EOS数量、IIF滴度进行了相关性分析,结果显示总IgE与激素应用最大剂量、EOS数量、IIF滴度均无相关性。激素应用的最大剂量可一定程度反映疾病的严重程度,疾病越重,所需激素的最大剂量越大。既往有研究显示EOS与BP间有明确的相关性,EOS的数量与病情的严重程度相关[13]。本研究组的初步研究结果显示BP患者EOS水平与激素应用剂量呈明显的正相关,EOS越高,激素应用剂量越高[14]。众所周知,IIF滴度不能作为评价疾病严重程度的指标,其原因是仅从IIF检测结果不能判定是BP180还是BP230占优势,抗BP180抗体滴度与BP的严重程度相关,而抗BP230抗体与BP的关系不明确[5]。本研究证实总IgE水平与反映病情严重程度的指标(激素应用的最大剂量、EOS水平)均无明显相关性,提示BP患者出现高IgE不能作为病情严重的指标,也不能根据IgE水平指导临床治疗。

    本研究中19例患者记录了治疗前后IgE的变化,其中18例患者是在一次病程中治疗前后的比较,1例患者是在病情复发时得到的数据。18例患者中14例患者治疗后IgE下降(但仅有2例患者降至正常水平),4例患者治疗后轻度升高,另有1例患者在病情复发时IgE升高。提示IgE水平随着病情的好转可有所下降,但即使临床得到完全缓解,其IgE水平仍超过正常。在2例有详细IgE记录的患者中,IgE水平与病情变化趋势相一致,当病情未控制时,IgE呈直线上升趋势,水疱控制后IgE达最高水平,此后IgE缓慢下降,高IgE持续时间与总IgE明显相关,IgE越高持续时间越长(目前的观察可长达2年)。若在疾病早期病情未控制时(IgE呈上升状态)采血测得IgE,即使病情控制后仍会出现治疗后IgE高于治疗前的假象。提示动态观察IgE水平对研究IgE与BP间的相关性至关重要。

    此外,本研究还就性别对IgE产生的影响作了分析。有报道表明妊娠妇女血清中抗BP180 IgE抗体水平明显高于非妊娠妇女[15],提示妊娠亦是抗体产生的原因之一。为排除妊娠导致IgE升高的因素,本研究对患者按性别进行分组,所有女性患者均有妊娠史,均无妊娠疱疹史,结果显示在不考虑病情严重程度、激素治疗剂量等因素的情况下,单独就性别比较,两组差异无统计学意义,证实妊娠并非IgE升高的因素。

    本研究的局限性: (1)本研究只评价了激素应用的最大剂量,而未对免疫抑制剂的应用情况进行分析。因为免疫抑制剂种类繁多,且无等量换算方法。(2)在既往的研究报道中,多数是以水疱的数量和皮损累及面积来衡量疾病的严重程度[5, 16],本研究中的部分病例不能完全再现患者入院时的状况,故未能通过上述临床指标评价患者病情的严重程度。(3)病例例数限制。

    总之,本研究结果显示BP患者血清中总IgE水平明显升高,但与病情严重程度无关。BP患者出现高IgE的确切机制有待进一步探讨。

  • 图  1   血清尿酸水平升高与颅内增强病灶数目减少显著相关(r = -0. 716,P =0. 009)

    表  1   β干扰素-1b对患者EDSS、年复发次数、颅内增强病灶数目及血清尿酸水平的影响

    时间 EDSS (中位数) 年复发次数(中位数) 颅内增强病灶数目(中位数) 尿酸(μmol/L,x ± s)
    治疗前(缓解期) 2.8 0.9 1.5 222. 2 ± 28. 9
    治疗后6个月 2.0 0.0 0.0 239. 4 ± 48. 7
    P 0.064 0.011 0.007 0.213
    EDSS:扩展残疾状态评分
    下载: 导出CSV
  • [1]

    Liu JS, Zhao ML, Brosnan CF, et al. Expression of inducible nitric oxide synthase and nitrotyrosine in multiple sclerosis lesions[J]. Am J Pathol, 2001, 158:2057-2066. DOI: 10.1016/S0002-9440(10)64677-9

    [2]

    Tran EH, Hardin-Pouzet H, Verge G, et al. Astrocytes and microglia express inducible nitric oxide synthase in mice with experimental allergic encephalomyelitis[J]. J Neuroimmunol, 1997, 74:121-129. DOI: 10.1016/S0165-5728(96)00215-9

    [3]

    Mitrovic B, Ignarro LJ, Montestruques S, et al. Nitric oxide as a potential pathological mechanism in demyelination:its differential effects on primary glial cells in vitro[J]. Neuroscience, 1994, 61:575-585. DOI: 10.1016/0306-4522(94)90435-9

    [4]

    Squadrito GL, Cueto R, Splenser AE, et al. Reaction of uric acid with peroxynitrite and implications for the mechanism of neuroprotection by uric acid[J]. Arch Biochem Biophys, 2000, 376:333-337. DOI: 10.1006/abbi.2000.1721

    [5]

    Scott GS, Spitsin SV, Kean RB, et al. Therapeutic intervention in experimental allergic encephalomyelitis by administration of uric acid precursors[J]. Proc Natl Acad Sci U S A, 2002, 99:16303-16308. DOI: 10.1073/pnas.212645999

    [6]

    Hooper DC, Spitsin K, Kean RB, et al. Uric acid, a natural scavenger of peroxynitrite, in experimental allergic encephalomyelitis and multiple sclerosis[J]. Proc Natl Acad Sci U S A, 1998, 95:675-680. DOI: 10.1073/pnas.95.2.675

    [7]

    Zamani A, Rezaei A, Khaeir F, et al. Serum and cerebrospinal fluid uric acid levels in multiple sclerosis patients[J]. Clin Neurol Neurosurg, 2008, 110:642-643. DOI: 10.1016/j.clineuro.2008.03.002

    [8]

    Sotgiu S, Pugliatti M, Sanna A, et al. Serum uric acid and multiple sclerosis[J]. Neurol Sci, 2002, 23:183-188. DOI: 10.1007/s100720200059

    [9]

    Rentzos M, Nikolaou C, Anagnostouli M, et al. Serum uric acid and multiple sclerosis[J]. Clin Neurol Neurosurg, 2006, 108:527-531. DOI: 10.1016/j.clineuro.2005.08.004

    [10]

    Spitsin S, Hooper DC, Mikheeva T, et al. Uric acid levels in patients with multiple sclerosis:analysis in mono- and dizygotic twins[J]. Mult Scler, 2001, 7:165-166. DOI: 10.1177/135245850100700305

    [11]

    Toncev G, Milicic B, Toncev S, et al. Serum uric acid levels in multiple sclerosis patients correlate with activity of disease and blood-brain barrier dysfunction[J]. Eur J Neurol, 2002, 9:221-226. DOI: 10.1046/j.1468-1331.2002.00384.x

    [12]

    Mostert JP, Ramsaransing SM, Heersema DJ, et al. Serum acid levels and leukocyte nitric oxide production in multiple sclerosis patients outside relapses[J]. J Neurol Sci, 2005, 231:41-44. DOI: 10.1016/j.jns.2004.12.008

    [13]

    Kastenbauer S, Kieseier BC, Becker BF. No evidence of increased oxidative degradation of urate to allantoin in the CSF and serum of patients with multiple sclerosis[J]. J Neurol, 2005, 252:611-612. DOI: 10.1007/s00415-005-0697-z

    [14]

    Ramsaransing GSM, Heersema DJ, De Keyser J. Serum uric acid, dehydroepiandrosterone sulphate, and apolipoprotein E genotype in benign vs. progressive multiple sclerosis[J]. Eur J Neurol, 2005, 12:514-518. DOI: 10.1111/j.1468-1331.2005.01009.x

    [15]

    Drulovic J, Dujmovic I, Stojsavljevic N, et al. Uric acid levels in sera from patients with multiple sclerosis[J]. J Neurol, 2001, 248:121-126. DOI: 10.1007/s004150170246

    [16]

    Karg E, Klivenyi P, Nemeth I, et al. Nonenzymatic antioxidants of blood in multiple sclerosis[J]. J Neurol, 1999, 246:533-539. DOI: 10.1007/s004150050399

    [17]

    Peng F, Zhang B, Zhong X, et al. Serum uric acid levels of patients with multiple sclerosis and other neurological diseases[J]. Mult Scler, 2008, 14:188-196. DOI: 10.1177/1352458507082143

    [18]

    Constantinescu C, Freitag P, Kappos L. Increase in serum levels of uric acid, endogenous antioxidant, under treatment with glatiramer acetate for multiple sclerosis[J]. Mult Scler, 2000, 6:378-381. DOI: 10.1177/135245850000600603

    [19]

    Guerrero AL, Martín-Polo J, Laherrán E, et al. Variation of serum uric acid levels in multiple sclerosis during relapses and immunomodulatory treatment[J]. Eur J Neurol, 2008, 15:394-397. DOI: 10.1111/j.1468-1331.2008.02087.x

    [20]

    Polman CH, Reingold SC, Edan G, et al. Diagnostic criteria for multiple sclerosis:2005 revisions to the "McDonald Criteria"[J]. Ann Neurol, 2005, 58:840-846. DOI: 10.1002/ana.20703

    [21]

    Lövblad KO, Anzalone N, Dörfler A, et al. MR imaging in multiple sclerosis:review and recommendations for current practice[J]. AJNR Am J Neuroradiol, 2010, 31:983-989. DOI: 10.3174/ajnr.A1906

    [22]

    Mowry EM, Beheshtian A, Waubant E, et al. Quality of life in multiple sclerosis is associated with lesion burden and brain volume measures[J]. Neurology, 2009, 72:1760-1785. DOI: 10.1212/WNL.0b013e3181a609f8

    [23]

    Brex PA, Molyneux PD, Smiddy P, et al. The effect of IFN beta-1b on the evolution of enhancing lesions in secondary progressive MS[J]. Neurology, 2001, 57:2185-2190. DOI: 10.1212/WNL.57.12.2185

    [24]

    Milanese C, Mantia LL, Palumbo R, et al. A post-marketing study on interferon-beta 1b and 1a treatment in relapsingremitting multiple sclerosis:different response in drop-outs and treated patients[J]. J Neurol Neurosurg Psychiatry, 2003, 74:1689-1692. DOI: 10.1136/jnnp.74.12.1689

    [25]

    Barkhof F, Polman CH, Radue EW, et al. Magnetic resonance imaging effects of interferon beta-1b in the BENEFIT study:integrated 2-year results[J]. Arch Neurol, 2007, 64:1292-1298. DOI: 10.1001/archneur.64.9.1292

    [26]

    Gaindh D, Jeffries N, Ohayon J, et al. The effect of interferon beta-1b on size of short-lived enhancing lesions in patients with multiple sclerosis[J]. Expert Opin Biol Ther, 2008, 8:1823-1829. DOI: 10.1517/14712590802510629

    [27]

    Khan OA, Tselis AC, Kamholz JA, et al. A prospective, open-label treatment trial to compare the effect of IFNβ-1a (Avonex), IFNβ-1b (Betaseron), and glatiramer acetate (Copaxone) on the relapse rate in relapsing-remitting multiple sclerosis[J]. Eur J Neurol, 2001, 8:141-148. DOI: 10.1046/j.1468-1331.2001.00189.x

    [28]

    Etemadifar M, Janghorbani M, Shaygannejad V. Comparison of Betaferon, Avonex, and Rebif in treatment of relapsing-remitting multiple sclerosis[J]. Acta Neurol Scand, 2006, 113:283-287. http://europepmc.org/abstract/MED/16629762

    [29]

    Flechter S, Vardi J, Finkelstein Y, et al. Cognitive dysfunction evaluation in multiple sclerosis patients treated with interferon beta-1b:an open-label prospective 1 year study[J]. Isr Med Assoc J, 2007, 9:457-459. http://www.ncbi.nlm.nih.gov/pubmed/17642394

    [30]

    Lily O, McFadden E, Hensor E, et al. Disease-specific quality of life in multiple sclerosis:the effect of disease modifying treatment[J]. Mult Scler, 2006, 12:808-813. DOI: 10.1177/1352458506070946

    [31]

    Trojano M, Paolicelli D, Zimatore GB, et al. The IFNbeta treatment of multiple sclerosis (MS) in clinical practice:the experience at the MS Center of Bari, Italy[J]. Neurol Sci, 2005, 26:S179-S182. DOI: 10.1007/s10072-005-0511-9

    [32]

    Trojano M, Liguori M, Paolicelli D, et al. Interferon beta in relapsing-remitting multiple sclerosis:an independent postmarketing study in southern Italy[J]. Mult Scler, 2003, 9:451-457. DOI: 10.1191/1352458503ms948oa

    [33]

    Flechter S, Vardi J, Pollak L, et al. Comparison of glatiramer acetate (Copaxone) and interferon beta-1b (Betaferon) in multiple sclerosis patients:an open-label 2-year follow-up[J]. J Neurol Sci, 2002, 197:51-55. DOI: 10.1016/S0022-510X(02)00047-3

    [34]

    Grossman RI, Braffman BH, Brorson JR, et al. Multiple sclerosis:serial study of gadolinium-enhanced MR imaging[J]. Radiology, 1988, 169:117-122. DOI: 10.1148/radiology.169.1.3420246

    [35]

    Jimenez J, Jy W, Mauro LM, et al. Elevated endothelial microparticle-monocyte complexes induced by multiple sclerosis plasma and the inhibitory effects of interferon-beta 1b on release of endothelial microparticles, formation and transendothelial migration of monocyte-endothelial microparticle complexes[J]. Mult Scler, 2005, 11:310-315. DOI: 10.1191/1352458505ms1184oa

    [36]

    Minagar A, Long A, Ma T, et al. Interferon (IFN) -beta 1a and IFN-beta 1b block IFN-gamma-induced disintegration of endothelial junction integrity and barrier[J]. Endothelium, 2003, 10:299-307. DOI: 10.1080/10623320390272299

    [37]

    Trojano M, Defazio G, Avolio C, et al. Effects of rIFN-beta-1b on serum circulating ICAM-1 in relapsing remitting multiple sclerosis and on the membrane-bound ICAM-1 expression on brain microvascular endothelial cells[J]. J Neurovirol, 2000, 6(Suppl 2):S47-S51. http://www.ncbi.nlm.nih.gov/pubmed/10871785

  • 期刊类型引用(5)

    1. 扈容英,苏雅丽,王立鹏,董灵娣,李可心,夏莉,喻楠. 大疱性类天疱疮85例回顾性临床分析. 实用皮肤病学杂志. 2023(06): 338-342 . 百度学术
    2. 潘春梅,潘萌,冯雨苗,丁高中,朱燕萍,孙澜. 度普利尤单抗治疗难治性大疱性类天疱疮1例. 中国皮肤性病学杂志. 2022(03): 311-314 . 百度学术
    3. 盖晓磊,左亚刚. 嗜酸性粒细胞在大疱性类天疱疮发病机制中的作用及临床应用. 中华临床免疫和变态反应杂志. 2020(03): 250-254 . 百度学术
    4. 周夕湲,廖金凤,薛竞,潘宁. 儿童大疱性类天疱疮5例分析. 实用皮肤病学杂志. 2019(04): 193-196 . 百度学术
    5. 赵英,吕玲,安蔚,贾艳辉. ELISA指数在大疱性类天疱疮治疗中的应用价值分析. 航空航天医学杂志. 2013(09): 1074-1075 . 百度学术

    其他类型引用(5)

图(1)  /  表(1)
计量
  • 文章访问数:  174
  • HTML全文浏览量:  46
  • PDF下载量:  5
  • 被引次数: 10
出版历程
  • 收稿日期:  2012-05-02
  • 刊出日期:  2012-07-29

目录

/

返回文章
返回
x 关闭 永久关闭