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METHOD FOR DIAGNOSING ACUTE LUNG INJURY

Foreign code F120006837
File No. S2011-0359
Posted date Sep 5, 2012
Country WIPO
International application number 2012JP053174
International publication number WO 2012108538
Date of international filing Feb 10, 2012
Date of international publication Aug 16, 2012
Priority data
  • P2011-027679 (Feb 10, 2011) JP
Title METHOD FOR DIAGNOSING ACUTE LUNG INJURY
Abstract The present invention provides a useful diagnostic method and a useful diagnostic agent which are capable of diagnosing acute lung injury in clear distinction from chronic progressive interstitial pneumonia. The present invention specifically provides a method for determining whether a subject is suffering from acute lung injury or not, said method comprising quantitative determination of heat shock protein 47 in a biological sample derived from the subject.
Outline of related art and contending technology BACKGROUND ART
Acute lung injury (Acute Lung Injury; also termed ALI) is, in a direct or indirect injury to the lungs of sepsis, diseases such as pneumonia, an injury or trauma, such as aspiration and/or malfunctions caused by an inflammatory disease of the lungs. Show nonspecific symptoms, dyspnea is the main symptom, sometimes with a cough or chest pain. Patients with acute lung injury, typically within 24-48 of the original injury or disease as indicated by the symptoms, leading to death in a serious case. Mortality rate is as high as 30-40%, to further increase the aging or Childhood.
Diagnosis of acute lung injury, which is basically performed by the clinical diagnosis. The clinical finding of acute lung injury, acute heart failure and lung infection is similar in both the clinical observations, a diagnosis and, in order to identify the cause, the patient any more ABG(Arterial Blood Gas; arterial blood gas test, the partial pressure of oxygen in the blood, CO2 partial pressure, measuring the pH and the like) and the chest of the subject to X-ray inspection thereof. However, acute lung injury is very rapidly, effective treatment has not been established, in a very poor prognosis of diseases. Pneumothorax or severe pulmonary complications such as bacterial infection which may develop. Therefore, in particular for early diagnosis is needed.
Recently, more convenient, in order to diagnose acute lung injury quickly as serum markers (sialic-carbohydrate antigen) KL-6, SP-D(Surfactant protein-D), SP-A(Surfactant protein-A) is such that the carrier can be used. However, these may be organized with idiopathic (cryptogenic organizing pneumonia pneumonia; COP), idiopathic normal interstitial (idiopathic usual interstitial pneumonia; idiopathic UIP), idiopathic nonspecific interstitial pneumonia (idiopathic nonspecific interstitial pneumonia; idiopathic NSIP), collagen-related normal interstitial (collagen vascular disease (CVD) -associated UIP), collagen-related nonspecific interstitial pneumonia (collagen vascular disease (CVD) -associated NSIP) and the like, chronic progressive interstitial known and are also markers, acute lung injury to clearly distinguish them for the diagnosis of, high specificity marker is not known.
Heat shock protein (HSP47) is 47, which has specificity for collagen and molecular chaperones, exists in the endoplasmic reticulum stress-induced heat shock has been known as a protein. HSP47 Expression, the expression of the collagen matrix from the conjugated, HSP47 in a variety of fibrotic diseases with the involvement is important has been pointed out (Patent Document 1-3, 8 and Non-Patent Document 6). In addition, acute lung injury in the role of the HSP47 phase of the fibrosis and the like are reported (non-patent document 1-3). Heretofore, fibrotic lung disease of the lung tissue topically to enhance HSP47 expression has been reported (Non-Patent Document 5 and 6), located within the endoplasmic reticulum HSP47 and does not leak to the outside of the cells which have been, with interstitial fibrosis (such as blood for example) in the extracellular in elevated HSP47 has not been considered. Reports are actually in idiopathic pulmonary fibrosis in the patient's serum and HSP47 healthy individuals with the same level, there is no increase in the clear (non-patent document 7). HSP47 Is, with a marked increase in acute lung injury and has been observed, acute lung injury and chronic progressive interstitial pneumonia can be clearly distinguished, is made to be useful biomarkers, it has not been known at all, which is not unexpected.
Scope of claims (In Japanese)請求の範囲 [請求項1]
 被験体由来の生体試料におけるヒートショックプロテイン47を定量することを含む、被験体が急性肺損傷に罹患しているか否かを判定するための方法。

[請求項2]
 急性肺損傷と慢性進行性間質性肺炎との判別方法である、請求項1に記載の方法。

[請求項3]
 急性肺損傷と大動脈解離、急性心不全、慢性心不全急性増悪、びまん性肺胞出血、癌性リンパ管症、再膨張性肺水腫、過剰輸液による肺水腫、神経原性肺水腫、肺結核、又は粟粒結核との判別方法である、請求項1に記載の方法。

[請求項4]
 生体試料が血液、血清又は血漿である、請求項1~3のいずれか1項に記載の方法。

[請求項5]
 ヒートショックプロテイン47を特異的に認識する抗体及び/又は、コラーゲン又はヒートショックプロテイン47との特異的結合性を有するその部分断片を含む、急性肺損傷の診断薬。

[請求項6]
 被験体由来の生体試料におけるヒートショックプロテイン47を定量することを含む、被験体が急性肺損傷を発症するか否かを判定するための方法。

[請求項7]
 被験体由来の生体試料におけるヒートショックプロテイン47を定量することを含む、被験体の急性肺損傷の治療効果を判定又は予後を予測するための方法。

  • Applicant
  • ※All designated countries except for US in the data before July 2012
  • NAGASAKI UNIVERSITY
  • SAPPORO MEDICAL UNIVERSITY
  • Inventor
  • KAKUGAWA, Tomoyuki
  • YOKOTA, Shin-ichi
IPC(International Patent Classification)
Specified countries National States: AE AG AL AM AO AT AU AZ BA BB BG BH BR BW BY BZ CA CH CL CN CO CR CU CZ DE DK DM DO DZ EC EE EG ES FI GB GD GE GH GM GT HN HR HU ID IL IN IS JP KE KG KM KN KP KR KZ LA LC LK LR LS LT LU LY MA MD ME MG MK MN MW MX MY MZ NA NG NI NO NZ OM PE PG PH PL PT QA RO RS RU RW SC SD SE SG SK SL SM ST SV SY TH TJ TM TN TR TT TZ UA UG US UZ VC VN ZA ZM ZW
ARIPO: BW GH GM KE LR LS MW MZ NA RW SD SL SZ TZ UG ZM ZW
EAPO: AM AZ BY KG KZ MD RU TJ TM
EPO: AL AT BE BG CH CY CZ DE DK EE ES FI FR GB GR HR HU IE IS IT LT LU LV MC MK MT NL NO PL PT RO RS SE SI SK SM TR
OAPI: BF BJ CF CG CI CM GA GN GQ GW ML MR NE SN TD TG
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