JP2017524130A - 膜性腎症をモニタリングするための方法およびキット - Google Patents
膜性腎症をモニタリングするための方法およびキット Download PDFInfo
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- JP2017524130A JP2017524130A JP2017503580A JP2017503580A JP2017524130A JP 2017524130 A JP2017524130 A JP 2017524130A JP 2017503580 A JP2017503580 A JP 2017503580A JP 2017503580 A JP2017503580 A JP 2017503580A JP 2017524130 A JP2017524130 A JP 2017524130A
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- thsd7a
- membranous nephropathy
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- autoantibodies
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Abstract
Description
(i)患者から取得された生物学的試料を、THSD7Aポリペプチドまたはその抗体結合性断片と接触させるステップ、および
(ii)形成された任意の抗原−抗体複合体を検出するステップ
を含み、抗原−抗体複合体の存在は膜性腎症を示す。
(i)第1の時点において、この第1の時点において患者から取得された試料中の抗THSD7A自己抗体のレベルを決定するステップ、
(ii)第2の時点において、この第2の時点において患者から取得された試料中の抗THSD7A自己抗体のレベルを決定するステップ、および
(iii)これら2つの時点の自己抗体のレベルを比較するステップ
を含み、
・第1の時点と比較した第2の時点における抗THSD7A自己抗体のレベルにおける減少は、その処置が有効であることを示し、かつ/または
・第1の時点と比較した第2の時点における抗THSD7A自己抗体のレベルにおける増加は、その処置が有効でないことを示す。
・THSD7Aポリペプチドまたはその抗体結合性断片、および
・生物学的試料中に存在する自己抗原と自己抗体との間で形成された抗原−抗体複合体の検出のための試薬
を含む。
(i)患者から取得された生物学的試料中のTHSD7Aタンパク質のレベルを測定するステップ、
(ii)このレベルを参照レベルと比較するステップ
を含み、参照レベルと比較したTHSD7Aタンパク質の増加したレベルは、膜性腎症を示す。
用語「膜性腎症」は、当技術分野におけるその一般的な意味を有し、成人ネフローゼ症候群のよくある原因である腎疾患を指す。これは、全身性エリテマトーデス、B型肝炎または梅毒(...)などの二次的要因によって引き起こされる二次性膜性腎症、および「特発性膜性腎症」とも呼ばれる原発性自己免疫性膜性腎症を包含する。「特発性膜性腎症」は、糸球体を標的化する自己免疫疾患であるとみなされ、主要な公知の標的抗原は自己抗原PLA2R1である。
診断方法
したがって、本発明の第1の目的は、患者における膜性腎症、より特には特発性膜性腎症を診断および/または予後判定するためのin vitro方法に関し、この方法は、患者から取得された生物学的試料中の、THSD7Aタンパク質を認識する1または複数の自己抗体を検出するステップを含む。
(i)患者から取得された生物学的試料を、THSD7Aポリペプチドまたはその抗体結合性断片と接触させるステップ、および
(ii)形成された任意の抗原−抗体複合体を検出するステップ
を含み、抗原−抗体複合体の存在は膜性腎症を示す。
本発明者らは、抗THS7A自己抗体の存在およびレベルと、膜性腎症、より具体的には特発性膜性腎症を有する患者の処置の有効性、寛解または再燃との間の相関もまた示した。
(i)第1の時点において、この第1の時点において患者から取得された試料中の抗THSD7A自己抗体のレベルを決定するステップ、
(ii)第2の時点において、この第2の時点において患者から取得された試料中の抗THSD7A自己抗体のレベルを決定するステップ、および
(iii)これら2つの時点の自己抗体のレベルを比較するステップ
を含み、
・第1の時点と比較した第2の時点における抗THSD7A自己抗体のレベルにおける減少は、その処置が有効であることを示し、および/または
・第1の時点と比較した第2の時点における抗THSD7A自己抗体のレベルにおける増加は、その処置が有効でないことを示す。
別の一態様では、本発明は、本発明に従う方法を実施するために有用な材料を含むキットを提供する。本明細書で提供される診断手順は、診断検査室、実験研究室または従事者によって実施され得る。本発明は、これらの異なる設定において使用され得るキットを提供する。
・THSD7Aポリペプチドまたはその抗体結合性断片、および
・自己抗原、好ましくはTHSD7Aポリペプチドまたはその抗体結合性断片と、生物学的試料中に存在する自己抗体、好ましくはTHSD7Aに対する自己抗体との間で形成された抗原−抗体複合体の検出のための試薬
を含む。
・THSD7Aポリペプチドまたはその抗体結合性断片、および
・自己抗原マーカーと、生物学的試料中に存在する自己抗体との間で形成された抗原−抗体複合体の検出のための試薬
を含み、本発明の方法に従って使用され得る。
本発明者らは、自己抗原THSD7Aが、膜性腎症に罹った患者、特に、特発性膜性腎症に罹った患者の腎臓において(特に、THSD7A自己抗体を有する患者において)、過剰発現されることを示した。
一実施形態では、本発明は、患者における膜性腎症、特に特発性膜性腎症を診断および/または予後判定するためのin vitro方法に関し、この方法は、患者から取得された生物学的試料中のTHSD7Aタンパク質のレベルを決定するステップを含む。
(i)患者から取得された生物学的試料中のTHSD7Aタンパク質のレベルを測定するステップ、
(ii)このレベルを参照レベルと比較するステップ
を含み、参照レベルと比較したTHSD7Aタンパク質の増加したレベルは、膜性腎症、特に特発性膜性腎症を示す。
別の一実施形態では、本発明は、患者における膜性腎症、特に特発性膜性腎症を診断および/または予後判定するためのin vitro方法に関し、この方法は、患者から取得された生物学的試料中のTHSD7A発現のレベルを決定するステップを含む。
(i)患者から取得された生物学的試料中のTHSD7A mRNAのレベルを測定するステップ、
(ii)このレベルを参照レベルと比較するステップ
を含み、参照レベルと比較したTHSD7A mRNAの増加したレベルは、膜性腎症、特に特発性膜性腎症を示す。
本発明者らは、有足細胞上で発現されるTHSD7Aタンパク質が、膜性腎症の特定の症例における自己抗原であることを強調し、このことが、この自己抗原を標的化することに基づく新規治療アプローチを想起することを可能にする。
患者。膜性腎症(MN)の診断を、腎生検によって行った。血清を、膜性腎症を有する患者、他の腎臓疾患を有する患者および健康な対照から採取した。全ての患者は、最初の血清を採取した時点では、先行する免疫抑制治療を有さなかった。血清を、ELISAによって、抗PLA2R1抗体について調査した。
PLA2R1のパラログおよびヒト糸球体由来のタンパク質溶解物による特発性膜性腎症血清のスクリーニング。本発明者らは、2つの並行するアプローチによって、特発性膜性腎症(iMN)血清および適切な対照血清をスクリーニングした。第1のアプローチは、候補抗原として、PLA2R1のパラログに焦点を当てた。第2のアプローチは、ヒト糸球体抽出物(HGE)由来の総タンパク質に対する、より一般的な血清のスクリーニングであった。
Claims (19)
- 患者における膜性腎症を診断および/または予後判定するためのin vitro方法であって、該患者から取得された生物学的試料中の、THSD7A(トロンボスポンジン、I型、ドメイン含有7A)タンパク質を認識する1または複数の自己抗体を検出するステップを含む、方法。
- (i)前記患者から取得された生物学的試料を、THSD7Aポリペプチドまたはその抗体結合性断片と接触させるステップ、および
(ii)形成された任意の抗原−抗体複合体を検出するステップ
を含み、抗原−抗体複合体の存在は膜性腎症を示す、請求項1に記載のin vitro方法。 - 前記膜性腎症が特発性膜性腎症である、請求項1または2に記載のin vitro方法。
- 前記生物学的試料が血液試料である、請求項1から3のいずれか一項に記載のin vitro方法。
- 前記患者がPLA2R1陰性患者である、請求項1から4のいずれか一項に記載のin vitro方法。
- 患者における膜性腎症、特に特発性膜性腎症に対する処置の有効性を評価するためのin vitro方法であって、
(i)第1の時点において、該第1の時点において該患者から取得された試料中の抗THSD7A自己抗体のレベルを決定するステップ、
(ii)第2の時点において、該第2の時点において該患者から取得された試料中の抗THSD7A自己抗体のレベルを決定するステップ、および
(iii)該2つの時点の自己抗体のレベルを比較するステップ
を含み、
・該第1の時点と比較した該第2の時点における抗THSD7A自己抗体のレベルにおける減少は、該処置が有効であることを示し、および/または
・該第1の時点と比較した該第2の時点における抗THSD7A自己抗体のレベルにおける増加は、該処置が有効でないことを示す、
方法。 - 前記THSD7Aポリペプチドまたはその断片でコーティングされたデバイスの使用を含む、請求項1から6のいずれか一項に記載の方法。
- 患者における膜性腎症を診断および/または予後判定するためのキットであって、
・THSD7Aポリペプチドまたはその抗体結合性断片、および
・THSD7Aポリペプチドまたはその抗体結合性断片と、生物学的試料中に存在するTHSD7Aに対する自己抗体との間で形成された抗原−抗体複合体の検出のための試薬
を含む、キット。 - PLA2R1ポリペプチドまたはその抗体結合性断片をさらに含む、請求項8に記載のキット。
- 患者における膜性腎症を診断および/または予後判定するためのin vitro方法であって、該患者から取得された生物学的試料中のTHSD7Aレベルを決定するステップを含む、方法。
- (i)前記患者から取得された生物学的試料中のTHSD7Aタンパク質のレベルを測定するステップ、
(ii)該レベルを参照レベルと比較するステップ
を含み、該参照レベルと比較したTHSD7Aタンパク質の増加したレベルは、膜性腎症を示す、請求項10に記載のin vitro方法。 - 前記膜性腎症が特発性膜性腎症である、請求項10または11に記載のin vitro方法。
- 前記生物学的試料が腎臓生検である、請求項10から12に記載のin vitro方法。
- 膜性腎症を処置するための使用のための、THSD7Aポリペプチドまたはその断片。
- 前記膜性腎症が特発性膜性腎症である、請求項14に記載の使用のためのTHSD7Aポリペプチドまたはその断片。
- 患者がTHSD7A陽性患者である、請求項14または15に記載の使用のためのTHSD7Aポリペプチドまたはその断片。
- THSD7Aポリペプチドまたはその断片でコーティングされたデバイス。
- THSD7Aポリペプチドまたはその断片および薬学的に許容されるキャリアを含む、医薬組成物。
- 膜性腎症を処置するための使用のための、請求項18に記載の医薬組成物。
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IT201700025190A1 (it) * | 2017-03-07 | 2018-09-07 | Pad 4 Di Emanuele Ghiggeri S A S | Metodo in vitro e kit per predire l’andamento clinico e la sensibilita’ ai farmaci nei pazienti con nefropatia membranosa |
CN111413506A (zh) * | 2018-01-30 | 2020-07-14 | 深圳市伯劳特生物制品有限公司 | 一种检测试纸条在制备检测pla2r抗体的试剂盒中的应用 |
CN108414748B (zh) * | 2018-01-30 | 2022-02-15 | 深圳市伯劳特生物制品有限公司 | 一种thsd7a抗体的检测试纸条及检测方法 |
CN108802375A (zh) * | 2018-08-06 | 2018-11-13 | 滴准生物科技(常州)有限公司 | 一种抗核抗体谱的检测试剂盒 |
US20210270832A1 (en) * | 2018-08-15 | 2021-09-02 | Mayo Foundation For Medical Education And Research | Methods and materials for identifying and treating membranous nephropathy |
CN109324043A (zh) * | 2018-10-17 | 2019-02-12 | 睿诺医疗科技(上海)有限公司 | 一种用于肾病检测的试剂盒、及其制备和使用方法 |
CN110702916B (zh) * | 2019-04-15 | 2022-06-21 | 四川大学华西医院 | 一种整合蛋白质组和糖蛋白组的定量分析方法 |
CN112195154B (zh) * | 2019-07-08 | 2024-03-29 | 江苏汇智生物科技有限公司 | 一种基因改造表达改造型pla2r受体的细胞及其应用 |
EP4010704A1 (en) | 2019-08-06 | 2022-06-15 | Euroimmun Medizinische Labordiagnostika AG | An improved autoantibody detection assay |
WO2021055767A1 (en) * | 2019-09-19 | 2021-03-25 | Mayo Foundation For Medical Education And Research | Methods and materials for identifying and treating membranous nephropathy |
US20230348610A1 (en) * | 2020-03-06 | 2023-11-02 | Mayo Foundation For Medical Education And Research | Methods and materials for identifying and treating membranous nephropathy |
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CN114689859A (zh) * | 2020-12-30 | 2022-07-01 | 广州市微米生物科技有限公司 | 一种膜性肾病抗体检测试剂 |
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