JP2018519525A5

JP2018519525A5 -

Info

Publication number: JP2018519525A5
Application number: JP2017568262A
Authority: JP
Filing date: 2016-06-28
Publication date: 2020-12-03
Anticipated expiration: 2036-06-28

Description

本発明の第1の側面により、IgG4関連疾患を検出またはモニタリングするための方法であって、サンプル中で、
（i）IgG重鎖クラス；
（ii）κ軽鎖およびλ軽鎖の両方に結合するIgG4重鎖クラス；
および場合によっては、
（iii）同じ重鎖クラスを有するが、κ軽鎖のみ、またはλ軽鎖のみに結合した免疫グロブリン
を有する、抗体の相対量の間の比を検出すること
を含み、
前記方法は、
（i）前記免疫グロブリンを前記免疫グロブリンに特異的な結合剤に結合させ、ここで前記結合剤は、基材に固定化されているか、レポーター分子と複合化されており、
（ii）前記結合剤に結合した、又はレポーター分子と複合化された免疫グロブリンを検出する、標識化された検出剤を使用すること
を含む、前記免疫グロブリンの定量的検出を含む、方法が提供される。 According to the first aspect of the present invention, a method for detecting or monitoring IgG4-related disease in a sample.
(I) IgG heavy chain class;
(Ii) IgG4 heavy chain class that binds to both κ and λ light chains;
And in some cases
(Iii) Includes detecting the ratio between relative amounts of antibody having the same heavy chain class but having immunoglobulins bound only to the κ light chain or only the λ light chain.
The method is
(I) The immunoglobulin is bound to a binding agent specific for the immunoglobulin, where the binding agent is immobilized on a substrate or complexed with a reporter molecule.
(Ii) Provided methods comprising the quantitative detection of the immunoglobulin, comprising the use of a labeled detector, which detects an immunoglobulin bound to or complexed with the reporter molecule. Will be done.

Claims

A method for detecting or monitoring IgG4-related disease of interest.
In the sample
(I) IgG heavy chain class; and (ii) IgG4 heavy chain bound to both κ and λ light chains ;
And in some cases
(Iii) Includes detecting the ratio between relative amounts of two or more immunoglobulins having the same heavy chain class but having immunoglobulins bound only to the κ light chain or only the λ light chain.
The method is
(I) The immunoglobulin is bound to a binding agent specific for the immunoglobulin, where the binding agent is immobilized on a substrate or complexed with a reporter molecule.
(Ii) bound to the binding agent, or detecting the complexed immunoglobulin with a reporter molecule, by binding assays involving the use of labeled detection agent, see it contains the quantitative detection of said immunoglobulin ,
The ratio is as follows:
(I) At least one binder specific for the IgG heavy chain class; and
a) A combination of an IgG4-heavy chain-specific binder bound to the κ light chain and a λ light chain specific binder; and / or
b) A combination of an IgG4-heavy chain-specific binder bound to the λ light chain and a κ light chain specific binder; and / or
c) A combination of an IgG4 heavy chain-specific binder bound to the κ light chain and an IgG4 heavy chain-specific binder bound to the λ light chain;
Or use
(Ii) A combination of an IgG4 heavy chain-specific binder bound to the κ light chain and an IgG4 heavy chain-specific binder bound to the λ light chain.
The method , which is determined using.

A method for detecting the amount of IgG4κ / λ hybrid molecule.
In the sample
(I) IgG heavy chain class; and <br/> (ii) κ IgG4 heavy chain attached to both the light chain and λ light chains;
And in some cases
(Iii) Includes detecting the amount of immunoglobulin having the same heavy chain class but with immunoglobulins bound only to the κ light chain or only the λ light chain.
The method is
(I) the immunoglobulin is bound to a binding agent specific for the immunoglobulin, where the binding agent is immobilized on a substrate or complexed with a reporter molecule, and (ii) said. bound to the binding agent, or detecting the complexed immunoglobulin with a reporter molecule, by binding assays involving the use of labeled detection agent, see contains the quantitative detection of said immunoglobulin,
The amount of the IgG4κ / λ hybrid molecule is as follows:
(I) At least one binder specific for the IgG heavy chain class; and
a) A combination of an IgG4-heavy chain-specific binder bound to the κ light chain and a λ light chain specific binder; and / or
b) A combination of an IgG4-heavy chain-specific binder bound to the λ light chain and a κ light chain specific binder; and / or
c) A combination of an IgG4 heavy chain-specific binder bound to the κ light chain and an IgG4 heavy chain class-specific binder bound to the λ light chain;
Or use
(Ii) A combination of an IgG4 heavy chain-specific binder bound to the κ light chain and an IgG4 heavy chain-specific binder bound to the λ light chain.
The method , which is determined using.

The method of claim 1 or 2 , wherein the IgG heavy chain class is IgG4.

The method of any one of claims 1-3 , wherein the ratio is determined using an enzyme-linked immunosorbent assay (ELISA) containing an antibody.

The method of claim 1 or 2 , wherein the binding is determined using flow cytometry or fluorescently labeled beads.

The sample according to claim 1 or 2 , wherein the sample is whole blood, plasma, serum, urine, cerebrospinal fluid, lymph, tissue, or tumor tissue, most typically whole blood, plasma, or serum. the method of.

The result is
i) Subject's response to treatment of IgG4-related disease ; and / or
ii) Removal of antigen from the subject's environment; and / or
iii) Further characterization of IgG4-related disease or allergic response,
The method of claim 1 or 2 , which is used to determine.

The method of claim 1 or 2 , further comprising determining the presence of IgG4 isoarotype K409.

The method of any one of claims 1-8 , further comprising the step of detecting the presence and / or amount of the free κ and / or free λ light chain in the sample.

The method of claim 9, wherein the ratio of the amount of free κ light chain to the amount of free λ light chain is determined.

The liberated κ light chain and / or the liberated λ light chains are detected by specific antibodies or binding agents to the liberated κ light chain and / or liberated λ light chains, to claim 9 or 1 0 The method described.

A method of determining the amount or percentage of kappa IgG4 heavy chain attached to both the light chain and λ light chains in the synthetic antibody preparation,
In the sample of the synthetic antibody preparation,
(I) IgG heavy chain class; and (ii) IgG4 heavy chain bound to both κ and λ light chains ;
And in some cases
(Iii) Includes detecting the ratio between relative amounts of two or more immunoglobulins having the same heavy chain class but having immunoglobulins bound only to the κ light chain or only the λ light chain.
The method is
(I) The immunoglobulin is bound to a binding agent specific for the immunoglobulin, where the binding agent is immobilized on a substrate or complexed with a reporter molecule.
(Ii) bound to the binding agent, or detecting the complexed immunoglobulin with a reporter molecule, by binding assays involving the use of labeled detection agent, see it contains the quantitative detection of said immunoglobulin ,
The amount or proportion of IgG4 heavy chains bound to both the κ and λ light chains is:
(I) At least one binder specific for the IgG heavy chain class; and
a) A combination of an IgG4-heavy chain-specific binder bound to the κ light chain and a λ light chain specific binder; and / or
b) A combination of an IgG4-heavy chain-specific binder bound to the λ light chain and a κ light chain specific binder; and / or
c) A combination of an IgG4 heavy chain-specific binder bound to the κ light chain and an IgG4 heavy chain class-specific binder bound to the λ light chain;
Or use
(Ii) A combination of an IgG4 heavy chain-specific binder bound to the κ light chain and an IgG4 heavy chain-specific binder bound to the λ light chain.
The method , which is determined using.

(I) At least one binder specific for the IgG heavy chain class; and
a) A combination of an IgG4-heavy chain-specific binder bound to the κ light chain and a λ light chain specific binder; and / or
b) A combination of an IgG4-heavy chain-specific binder bound to the λ light chain and a κ light chain specific binder; and / or
c) A combination of an IgG4 heavy chain-specific binder bound to the κ light chain and an IgG4 heavy chain class-specific binder bound to the λ light chain; or
(Ii) A combination of an IgG4 heavy chain-specific binder bound to the κ light chain and an IgG4 heavy chain-specific binder bound to the λ light chain;
And in some cases,
(Iii) IgG4-specific binders and IgG-heavy chain class-specific binders ,
Assay kit containing.

Comprising a substantially pure IgG4κ / λ hybrid predetermined amount, the assay kit according to claim 1 3.

A method performed by claims 1 3 or 1 4 assay kit,
(I) binding agents specific for the IgG heavy chain class; and,
a) A combination of an IgG heavy chain class-specific binder bound to the κ light chain and a κ light chain specific binder; and / or
b) A combination of an IgG heavy chain class specific binder bound to the λ light chain and a λ light chain specific binder; and / or
c) A combination of an IgG heavy chain class-specific binder bound to the κ light chain and an IgG heavy chain class-specific binder bound to the λ light chain;
A method in which the ratio between the relative amounts of two or more immunoglobulins is detected.

(I) With a binder specific for IgG4 κ light chain;
(Ii) With a binder specific for IgG4 λ light chain;
(Iii) a predetermined amount substantially pure IgG4λ / κ hybrid to include <br/>, assay kit.

The method or kit according to any one of claims 1 to 16 , wherein the binder or detection agent is an antigen-specific aptamer, antibody, or antigen-specific fragment thereof.