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    Methods of diagnosing clinical subtypes of crohn's disease with characteristic responsiveness to anti-Th1 cytokine therapy
    1.
    发明授权
    Methods of diagnosing clinical subtypes of crohn's disease with characteristic responsiveness to anti-Th1 cytokine therapy 失效
    诊断克罗恩病临床亚型的方法具有抗Th1细胞因子治疗的特征反应

    公开(公告)号：US06183951B2

    公开(公告)日：2001-02-06

    申请号：US08855825

    申请日：1997-05-12

    申请人： Scott E. Plevy ,  Stephan R. Targan ,  Kent Taylor ,  Mary J. Barry

    发明人： Scott E. Plevy ,  Stephan R. Targan ,  Kent Taylor ,  Mary J. Barry

    IPC分类号： C12Q168

    CPC分类号： G01N33/6863 ,  C07K14/525 ,  G01N33/564 ,  G01N2333/525 ,  G01N2800/52

    摘要： The present invention provides methods based on serological and genetic markers for diagnosing clinical subtypes of Crohn's disease (CD) having characteristic responsiveness to anti-Th1 cytokine therapy. In the methods of the inventions the presence of perinuclear anti-neutrophil antibody (pANCA), the presence of the TNFa10b4c1d3e3 haplotype or the presence TNFa11b4c1d3e3 haplotype each are independently diagnostic of a clinical subtype of CD having an inferior clinical response to anti-Th1 cytokine therapy. In addition, the presence of the homozygous TNF-&bgr; 1111 haplotype involving the TNFc, aa13L, aa26 and NcoI loci is independently diagnostic of a clinical subtype of CD having an inferior clinical response to anti-Th1 cytokine therapy. The presence of speckling anti-pan polymorphonuclear antibody (SAPPA) is diagnostic of a clinical subtype of CD having a superior clinical response to anti-Th1 cytokine therapy.

    摘要翻译： 本发明提供了用于诊断对抗Th1细胞因子治疗具有特征反应性的克罗恩病（CD）的临床亚型的血清学和遗传标记物的方法。 在本发明的方法中，核周抗中性粒细胞抗体（pANCA）的存在，TNFa10b4c1d3e3单倍型的存在或TNFa11b4c1d3e3单元型的存在各自独立地诊断对抗Th1细胞因子治疗具有差的临床反应的CD的临床亚型 。 此外，涉及TNFc，aa13L，aa26和NcoI基因座的纯合TNF-β1111单体型的存在独立地诊断对抗Th1细胞因子治疗具有差的临床反应的CD的临床亚型。 斑点型抗泛型多形核抗体（SAPPA）的存在是对抗Th1细胞因子治疗具有优越临床反应的CD的临床亚型的诊断。

    Methods of diagnosing clinical subtypes of crohn's disease
    2.
    发明授权
    Methods of diagnosing clinical subtypes of crohn's disease 失效
    诊断克罗恩病临床亚型的方法

    公开(公告)号：US5932429A

    公开(公告)日：1999-08-03

    申请号：US837059

    申请日：1997-04-11

    申请人： Stephan R. Targan ,  Eric A. Vasiliauskas ,  Scott E. Plevy ,  Mary J. Barry

    发明人： Stephan R. Targan ,  Eric A. Vasiliauskas ,  Scott E. Plevy ,  Mary J. Barry

    IPC分类号： C12Q1/68 ,  G01N33/569 ,  G01N33/68 ,  G01N33/564

    CPC分类号： C12Q1/6883 ,  G01N33/56972 ,  G01N33/6893 ,  G01N2800/065 ,  Y10S435/975

    摘要： Provided herein is a method of diagnosing a clinical subtype of Crohn's disease (CD) by determining whether perinuclear anti-neutrophil antibody (pANCA) is present in a patient with CD, where the presence of pANCA indicates a clinical subtype of CD with features of ulcerative colitis (UC). Also provided is a method of diagnosing a clinical subtype of Crohn's disease in a patient with CD by determining whether pANCA or speckling anti-pan polymorphonuclear antibody (SAPPA) is present in the patient with CD, where the presence of pANCA indicates a clinical subtype of CD with features of ulcerative colitis and where the presence of SAPPA indicates a clinical subtype of CD having perforating, fistulizing or small bowel obstructive disease. The invention further provides a method of diagnosing a clinical subtype of Crohn's disease in a patient with CD by determining the presence or absence of ANCA, pANCA, SAPPA and anti-Saccharomyces cerevisiae antibodies (ASCA) in the patient with CD, where the presence of pANCA combined with the absence of ASCA indicate a clinical subtype of CD with features of UC, the presence of SAPPA indicates a clinical subtype of CD having perforating or fistulizing disease or small bowel obstructive disease, and the presence of ASCA combined with the absence of ANCA indicates a clinical subtype of CD lacking features of ulcerative colitis and having perforating or fistulizing disease or small bowel obstructive disease. Kits for diagnosing a clinical subtype of Crohn's disease, which contain neutrophil and antigen specific for ASCA, also are provided.

    摘要翻译： 本文提供了通过确定是否存在CD患者中存在核周抗中性粒细胞抗体（pANCA）来诊断克罗恩病（CD）的临床亚型的方法，其中pANCA的存在表示具有溃疡特征的CD的临床亚型 结肠炎（UC）。 还提供了通过确定患有CD的患者中是否存在pANCA或斑点抗泛多晶核抗体（SAPPA）来诊断患有CD的克罗恩病的临床亚型的方法，其中pANCA的存在表示临床亚型 CD具有溃疡性结肠炎的特征，并且其中SAPPA的存在表示具有穿孔，瘘管或小肠阻塞性疾病的CD的临床亚型。 本发明还提供了一种通过在CD患者中确定ANCA，pANCA，SAPPA和抗Saccharomyces cerevisiae抗体（ASCA）的存在或不存在来诊断患有CD的克罗恩病的临床亚型的方法，其中 与无ASCA相结合表明具有UC特征的CD的临床亚型，SAPPA的存在表明CD具有穿孔或瘘阻碍性疾病或小肠阻塞性疾病的临床亚型，并且ASCA的存在与不存在ANCA 表示缺乏溃疡性结肠炎特征的CD的临床亚型，具有穿孔或瘘管疾病或小肠阻塞性疾病。 还提供了用于诊断克罗恩病临床亚型的试剂盒，其中含有嗜中性粒细胞和ASCA特异性抗原。

    Methods of screening for Crohn's disease using TNF microsatellite alleles
    3.
    发明授权
    Methods of screening for Crohn's disease using TNF microsatellite alleles 有权
    使用TNF微卫星等位基因筛选克罗恩病的方法

    公开(公告)号：US06534263B1

    公开(公告)日：2003-03-18

    申请号：US09419406

    申请日：1999-10-15

    申请人： Scott E. Plevy ,  Jerome I. Rotter ,  Stephan R. Targan ,  Hiroo Toyoda ,  Huiying Yang

    发明人： Scott E. Plevy ,  Jerome I. Rotter ,  Stephan R. Targan ,  Hiroo Toyoda ,  Huiying Yang

    IPC分类号： C12Q1568

    CPC分类号： C12Q1/6858 ,  C12Q1/6883 ,  C12Q2600/156 ,  C12Q2600/172

    摘要： A novel association between certain tumor necrosis factor microsatellite alleles and Crohn's disease has been discovered. In accordance with the present invention, there is provided methods for screening for Crohn's disease comprising detecting the presence or absence of nucleic acid of a subject encoding TNF microsatellite alleles associated with Crohn's disease, wherein the presence of nucleic acid encoding three or more of the alleles is indicative of Crohn's disease. Kits useful for screening for Crohn's disease are also provided which comprise nucleic acid encoding TNF microsatellite alleles associated with Crohn's disease.

    摘要翻译： 已经发现了某些肿瘤坏死因子微卫星等位基因与克罗恩病之间的关联。 根据本发明，提供了用于筛选克罗恩病的方法，包括检测编码与克罗恩病相关的TNF微卫星等位基因的受试者的核酸的存在或不存在，其中编码三个或更多个等位基因的核酸的存在 表明克罗恩病。 还提供了用于筛选克罗恩病的试剂盒，其包含编码与克罗恩病相关的TNF微卫星等位基因的核酸。

    Method of diagnosing a clinical subtype of crohn's disease with features of ulcerative colitis
    5.
    发明授权
    Method of diagnosing a clinical subtype of crohn's disease with features of ulcerative colitis 失效
    诊断具有溃疡性结肠炎特征的克罗恩病的临床亚型的方法

    公开(公告)号：US5916748A

    公开(公告)日：1999-06-29

    申请号：US689873

    申请日：1996-08-15

    申请人： Stephan R. Targan ,  Eric A. Vasiliauskas ,  Scott E. Plevy ,  Huiying Yang ,  Jerome I. Rotter

    发明人： Stephan R. Targan ,  Eric A. Vasiliauskas ,  Scott E. Plevy ,  Huiying Yang ,  Jerome I. Rotter

    IPC分类号： C12Q1/68 ,  G01N33/569 ,  G01N33/68 ,  G01N33/564

    CPC分类号： G01N33/6893 ,  C12Q1/6883 ,  G01N33/56972 ,  C12Q2600/112 ,  C12Q2600/156 ,  G01N2800/065

    摘要： The present invention provides a method of diagnosing a clinical subtype of Crohn's disease (CD) by determining whether perinuclear anti-neutrophil antibodies (pANCA) are present in a patient with CD, where the presence of pANCA indicates the clinical subtype of CD with features of ulcerative colitis (UC). The invention also provides a method of diagnosing a clinical subtype of CD by detecting an Arg.sup.241 allele at an ICAM-1 locus in a patient with CD, where the Arg.sup.241 allele indicates a clinical subtype of CD with features of ulcerative colitis. In addition, the invention provides a method of diagnosing a pANCA-positive subtype of CD by detecting an Arg.sup.241 allele at an ICAM-1 locus in a patient with CD, where the Arg.sup.241 allele indicates the pANCA-positive subtype of CD.

    摘要翻译： 本发明提供了一种诊断克罗恩氏病（CD）的临床亚型的方法，该方法是通过确定是否存在CD患者中的核周抗中性粒细胞抗体（pANCA），其中pANCA的存在表示CD的临床亚型， 溃疡性结肠炎（UC）。 本发明还提供了通过检测患有CD的患者的ICAM-1位点处的Arg241等位基因来诊断CD的临床亚型的方法，其中Arg241等位基因表示具有溃疡性结肠炎特征的CD的临床亚型。 另外，本发明提供了通过检测患有CD的患者中ICAM-1位点处的Arg241等位基因来诊断CD的pANCA阳性亚型的方法，其中Arg241等位基因指示CD的pANCA阳性亚型。

    Methods of diagnosing a medically resistant clinical subtype of ulcerative colitis
    6.
    发明授权
    Methods of diagnosing a medically resistant clinical subtype of ulcerative colitis 失效
    诊断溃疡性结肠炎的耐药性临床亚型的方法

    公开(公告)号：US5968741A

    公开(公告)日：1999-10-19

    申请号：US837302

    申请日：1997-04-11

    申请人： Scott E. Plevy ,  Stephan R. Targan

    发明人： Scott E. Plevy ,  Stephan R. Targan

    IPC分类号： C12Q1/68 ,  G01N33/569 ,  G01N33/68

    CPC分类号： C12Q1/6883 ,  G01N33/56961 ,  G01N33/6893 ,  C12Q2600/106 ,  C12Q2600/156 ,  C12Q2600/172 ,  G01N2800/065

    摘要： The present invention provides serological and genetic methods of diagnosing a medically resistant clinical subtype of ulcerative colitis UC. The present invention provides a method of diagnosing a medically resistant clinical subtype of UC by determining the presence or absence of anti-Saccharomyces cerevisiae antibodies (ASCA) in a patient with UC, where the presence of ASCA indicates the medically resistant clinical subtype of UC. The present invention also provides a method of diagnosing a medically resistant clinical subtype of UC by determining the presence or absence of a TNFa2b1c2d4e1 haplotype in a patient with UC, where the presence of said TNFa2b1c2d4e1 haplotype indicates the medically resistant clinical subtype of UC. In addition, the invention provides a method of diagnosing a medically resistant clinical subtype of UC by determining the presence or absence of a TNFa2b1c2d4e1 haplotype in a patient with UC and determining the presence or absence of ASCA in the patient with UC, where the presence of said TNFa2b1c2d4e1 haplotype indicates the medically resistant clinical subtype of UC and the presence of ASCA independently indicates the medically resistant clinical subtype of UC. The invention further provides kits for diagnosing a medically resistant clinical subtype of UC containing antigen specific for ASCA and one or more oligonucleotide primers complementary to a nucleotide sequence flanking TNF microsatellite locus TNFa, TNFb, TNFc, TNFd or TNFe.

    摘要翻译： 本发明提供诊断溃疡性结肠炎UC的医学抗性临床亚型的血清学和遗传学方法。 本发明提供一种通过测定UC患者中存在或不存在抗Saccharomyces cerevisiae抗体（ASCA）来诊断UC的耐药性临床亚型的方法，其中ASCA的存在表示UC的耐药性临床亚型。 本发明还提供了通过确定UC患者中TNFα2b1c2d4e1单元型的存在或不存在来诊断UC的耐药性临床亚型的方法，其中所述TNFa2b1c2d4e1单元型的存在表示UC的耐药性临床亚型。 另外，本发明提供了通过在UC患者中确定TNFa2b1c2d4e1单元型的存在或不存在来确定UC的耐药性临床亚型的方法，并且确定UC患者中是否存在ASCA，其中存在 所述TNFa2b1c2d4e1单体型表示UC的耐药性临床亚型，ASCA的存在独立地表示UC的耐药性临床亚型。 本发明进一步提供用于诊断包含ASCA特异性抗原的UC的耐药性临床亚型的试剂盒和与TNF微卫星位点TNFa，TNFb，TNFc，TNFd或TNFe侧翼的核苷酸序列互补的一个或多个寡核苷酸引物。

    Methods of determining the risk of pouchitis development
    7.
    发明授权
    Methods of determining the risk of pouchitis development 失效
    确定囊泡发育风险的方法

    公开(公告)号：US5937862A

    公开(公告)日：1999-08-17

    申请号：US833388

    申请日：1997-04-04

    申请人： Stephan R. Targan ,  Phillip Fleshner ,  Scott E. Plevy

    发明人： Stephan R. Targan ,  Phillip Fleshner ,  Scott E. Plevy

    IPC分类号： G01N33/569 ,  G01N33/68 ,  A61B19/00

    CPC分类号： G01N33/6893 ,  G01N33/56972 ,  G01N2800/065

    摘要： Provided is a method of determining a risk of pouchitis development following a surgical procedure whereby colon is removed and an internal pouch is created in a patient with UC by determining a first pANCA titer, where the first pANCA titer is determined following the surgical procedure; determining a second pANCA titer at a later time; and comparing the first pANCA titer and the second pANCA titer, where a significantly elevated second pANCA titer indicates an increased risk of pouchitis development. Also provided is a method of determining a risk of pouchitis development following a surgical procedure whereby colon is removed and an internal pouch is created in a patient with UC by determining a first pANCA titer, where the first pANCA titer is determined prior to the surgical procedure; determining a second pANCA titer following said surgical procedure; and comparing the first pANCA titer and the second pANCA titer, where a significantly elevated second pANCA titer indicates an increased risk of pouchitis development.

    摘要翻译： 提供了一种在外科手术之后确定肠壁炎发展的风险的方法，其中通过确定第一pANCA滴度来确定第一pANCA滴度，其中在手术过程之后确定第一pANCA滴度，除去结肠并在患有UC的患者中产生内部小袋。 在稍后时间确定第二个pANCA滴度; 并比较第一个pANCA滴度和第二个pANCA滴度，其中明显升高的第二个pANCA滴度表明发生囊泡炎的风险增加。 还提供了一种在外科手术之后确定囊泡炎发展的风险的方法，其中结肠被移除并且通过确定第一pANCA滴度在患有UC的患者中产生内部小袋，其中在外科手术之前确定第一pANCA滴度 ; 在所述外科手术之后确定第二pANCA滴度; 并比较第一个pANCA滴度和第二个pANCA滴度，其中明显升高的第二个pANCA滴度表明发生囊泡炎的风险增加。

    Methods of diagnosing a clinical subtype of Crohn's disease with features of ulcerative colitis
    8.
    发明授权
    Methods of diagnosing a clinical subtype of Crohn's disease with features of ulcerative colitis 失效
    诊断具有溃疡性结肠炎特征的克罗恩病的临床亚型的方法

    公开(公告)号：US5874233A

    公开(公告)日：1999-02-23

    申请号：US689870

    申请日：1996-08-15

    申请人： Stephan R. Targan ,  Eric A. Vasiliauskas ,  Scott E. Plevy

    发明人： Stephan R. Targan ,  Eric A. Vasiliauskas ,  Scott E. Plevy

    IPC分类号： C12Q1/68 ,  G01N33/569 ,  G01N33/68 ,  G01N33/543 ,  G01N33/564

    CPC分类号： C12Q1/6883 ,  G01N33/56972 ,  G01N33/6893 ,  G01N2800/065

    摘要： The present invention provides a method of diagnosing a clinical subtype of Crohn's disease (CD) by determining whether perinuclear anti-neutrophil antibodies (pANCA) are present in a patient with CD, where the presence of pANCA indicates the clinical subtype of CD with features of ulcerative colitis (UC). The invention also provides a method of diagnosing a clinical subtype of CD by detecting an Arg.sup.241 allele at an ICAM-1 locus in a patient with CD, where the Arg.sup.241 allele indicates a clinical subtype of CD with features of ulcerative colitis. In addition, the invention provides a method of diagnosing a pANCA-positive subtype of CD by detecting an Arg.sup.241 allele at an ICAM-1 locus in a patient with CD, where the Arg.sup.241 allele indicates the pANCA-positive subtype of CD.

    摘要翻译： 本发明提供了一种诊断克罗恩氏病（CD）的临床亚型的方法，该方法是通过确定是否存在CD患者中的核周抗中性粒细胞抗体（pANCA），其中pANCA的存在表示CD的临床亚型， 溃疡性结肠炎（UC）。 本发明还提供了通过检测患有CD的患者的ICAM-1位点处的Arg241等位基因来诊断CD的临床亚型的方法，其中Arg241等位基因表示具有溃疡性结肠炎特征的CD的临床亚型。 另外，本发明提供了通过检测患有CD的患者中ICAM-1位点处的Arg241等位基因来诊断CD的pANCA阳性亚型的方法，其中Arg241等位基因指示CD的pANCA阳性亚型。