Method for measuring vanin-1 protein by latex agglutination method, measurement reagent, and measurement kit

Abstract

Provided are: a method for measuring vanin-1 in a sample by a latex agglutination method; and a reagent and a kit used for the method. Disclosed is a method for measuring vanin-1 in a sample by a latex agglutination method, the measurement method using: first latex particles carrying a first anti-vanin-1 antibody such as an anti-vanin-1 antibody having a heavy chain CDR1 comprising the amino acid sequence represented by SEQ ID NO: 1, a heavy chain CDR2 comprising the amino acid sequence represented by SEQ ID NO: 2, a heavy chain CDR3 comprising the amino acid sequence represented by SEQ ID NO: 3, a light chain CDR1 comprising the amino acid sequence represented by SEQ ID NO: 4, a light chain CDR2 comprising the amino acid sequence represented by SEQ ID NO: 5, and a light chain CDR3 comprising the amino acid sequence represented by SEQ ID NO: 6, or an antigen-binding fragment of the first anti-vanin-1 antibody; and second latex particles carrying a second anti-vanin-1 antibody different from the first anti-vanin-1 antibody or an antigen-binding fragment of the second anti-vanin-1 antibody.

Description

Method for measuring Vanin-1 protein, measurement reagent, and measurement kit by latex agglutination method

[0001] The present disclosure includes a method for measuring Vanin-1 protein (hereinafter, may be simply referred to as "Vanin-1") in a sample by latex agglutination method, and reagents and kits used in the method.

[0002] Vanin-1 in urine is a renal function marker that has been reported to increase with cisplatin-induced kidney injury (Non-Patent Document 1) and with decreased renal function in hypertensive patients (Non-Patent Document 2).

[0003] K. Hosohata et al., Toxicology, 2016; 359-360:71-75K. Hosohata et al., J Clin Hypertens. 2021; 23:1316-1321

[0004] In Non-Patent Documents 1 and 2, Vanin-1 was measured using a commercially available ELISA measurement kit (Cloud Clone).

[0005] The object of the present invention includes providing a method for measuring Vanin-1 in a sample by latex agglutination method, and reagents and kits used in the method.

[0006] As a result of intensive studies to achieve the above object, the present inventors have found a method for measuring Vanin-1 in a sample by latex agglutination method, and reagents and kits used in the method. Based on this finding, the present inventors have further intensively studied to complete the present invention.

[0007] The present invention includes the aspects described in the following items.

[0008] [Item 1] A method for measuring Vanin-1 in a sample by latex agglutination, comprising: a first latex particle carrying a first anti-Vanin-1 antibody or its antigen-binding fragment selected from (A) to (G) below; and a second latex particle carrying a second anti-Vanin-1 antibody or its antigen-binding fragment selected from (A) to (G) below and different from the first anti-Vanin-1 antibody: (A) An anti-vanin-1 antibody comprising a heavy chain CDR1 containing the amino acid sequence indicated by GFSITTTNYW (SEQ ID NO: 1), a heavy chain CDR2 containing the amino acid sequence indicated by ISYDGNT (SEQ ID NO: 2), a heavy chain CDR3 containing the amino acid sequence indicated by TSGWLLSLAEWG (SEQ ID NO: 3), a light chain CDR1 containing the amino acid sequence indicated by SEHSSSY (SEQ ID NO: 4), a light chain CDR2 containing the amino acid sequence indicated by LKSDGSH (SEQ ID NO: 5), and a light chain CDR3 containing the amino acid sequence indicated by GVAYSGGYV (SEQ ID NO: 6); (B) An anti-vanin-1 antibody comprising a heavy chain CDR1 containing the amino acid sequence indicated by GFTFSNYW (SEQ ID NO: 7), a heavy chain CDR2 containing the amino acid sequence indicated by INSDSSTM (SEQ ID NO: 8), a heavy chain CDR3 containing the amino acid sequence indicated by MTSGGLWG (SEQ ID NO: 9), a light chain CDR1 containing the amino acid sequence indicated by QSLLYSGNNNNY (SEQ ID NO: 10), a light chain CDR2 containing the amino acid sequence indicated by LAS, and a light chain CDR3 containing the amino acid sequence indicated by MQTFGIPRT (SEQ ID NO: 11); (C) An anti-vanin-1 antibody comprising a heavy chain CDR1 containing the amino acid sequence indicated by GFTFSNWY (SEQ ID NO: 12), a heavy chain CDR2 containing the amino acid sequence indicated by ISADSSDI (SEQ ID NO: 13), a heavy chain CDR3 containing the amino acid sequence indicated by ADISGSGI (SEQ ID NO: 14), a light chain CDR1 containing the amino acid sequence indicated by QSLLSSGNNKNY (SEQ ID NO: 15), a light chain CDR2 containing the amino acid sequence indicated by LAS, and a light chain CDR3 containing the amino acid sequence indicated by MQDYSVPLT (SEQ ID NO: 16);(D) An anti-vanin-1 antibody comprising a heavy chain CDR1 containing the amino acid sequence indicated by GFSLTSYS (SEQ ID NO: 17), a heavy chain CDR2 containing the amino acid sequence indicated by IWSDGSP (SEQ ID NO: 18), a heavy chain CDR3 containing the amino acid sequence indicated by ARDWGSLDV (SEQ ID NO: 19), a light chain CDR1 containing the amino acid sequence indicated by QSISRY (SEQ ID NO: 20), a light chain CDR2 containing the amino acid sequence indicated by YTN, and a light chain CDR3 containing the amino acid sequence indicated by QQYHSWPYT (SEQ ID NO: 21); (E) An anti-vanin-1 antibody comprising a heavy chain CDR1 containing the amino acid sequence indicated by GFTFSNDY (SEQ ID NO: 22), a heavy chain CDR2 containing the amino acid sequence indicated by ISGDSNYI (SEQ ID NO: 23), a heavy chain CDR3 containing the amino acid sequence indicated by ARHIAAYYFNL (SEQ ID NO: 24), a light chain CDR1 containing the amino acid sequence indicated by SVNNNF (SEQ ID NO: 25), a light chain CDR2 containing the amino acid sequence indicated by RTS, and a light chain CDR3 containing the amino acid sequence indicated by QQSSNDLT (SEQ ID NO: 26); (F) An anti-vanin-1 antibody comprising a heavy chain CDR1 containing the amino acid sequence indicated by GLTLSNSW (SEQ ID NO: 27), a heavy chain CDR2 containing the amino acid sequence indicated by INGDSRNI (SEQ ID NO: 28), a heavy chain CDR3 containing the amino acid sequence indicated by AASLDYYGLDI (SEQ ID NO: 29), a light chain CDR1 containing the amino acid sequence indicated by GLGNKY (SEQ ID NO: 30), a light chain CDR2 containing the amino acid sequence indicated by EDS, and a light chain CDR3 containing the amino acid sequence indicated by AIALGSGSGFHV (SEQ ID NO: 31); and (G) An anti-vanin-1 antibody comprising a heavy chain CDR1 containing the amino acid sequence indicated by GFTFSNSW (SEQ ID NO: 32), a heavy chain CDR2 containing the amino acid sequence indicated by INGDSTNI (SEQ ID NO: 33), a heavy chain CDR3 containing the amino acid sequence indicated by AAGPEYYSRNSYYMPFQY (SEQ ID NO: 34), a light chain CDR1 containing the amino acid sequence indicated by SDISVGRKS (SEQ ID NO: 35), a light chain CDR2 containing the amino acid sequence indicated by YYSDSDK (SEQ ID NO: 36), and a light chain CDR3 containing the amino acid sequence indicated by TIWHSGTWV (SEQ ID NO: 37).

[0009] [Item 2] The method according to item 1, wherein the first anti-Vanin-1 antibody is anti-Vanin-1 antibody (A).

[0010] [Item 3] The method according to item 1 or 2, wherein the second anti-Vanin-1 antibody is anti-Vanin-1 antibody (B) or (C).

[0011] [Item 4] The method according to any one of items 1 to 3, wherein the average particle diameter of the first and second latex particles is 100 to 500 nm, respectively.

[0012] [Item 5] The method according to any one of items 1 to 4, wherein a latex particle liquid is used in which the total concentration of the first and second latex particles is 0.005 to 0.5% by mass.

[0013] [Item 6] The method according to any one of items 1 to 5, wherein the measurement is a qualitative measurement, a semi-quantitative measurement, or a quantitative measurement.

[0014] [Item 7] The method according to any one of items 1 to 6, wherein the specimen is selected from urine, blood, serum, plasma, and interstitial fluid.

[0015] [Clause 8] The method of paragraph 7, which suggests that the subject from whom the sample was collected has kidney disease when the measured value obtained based on the measurement of the sample is greater than or equal to a reference value.

[0016] [Item 9] Reagents or kits for measuring Vanin-1 in a sample by latex agglutination, comprising a first anti-Vanin-1 antibody or its antigen-binding fragment selected from (A) to (G) below, and a second anti-Vanin-1 antibody or its antigen-binding fragment selected from (A) to (G) below and different from the first anti-Vanin-1 antibody: (A) An anti-Vanin-1 antibody having a heavy chain CDR1 containing the amino acid sequence indicated by GFSITTTNYW (SEQ ID NO: 1), a heavy chain CDR2 containing the amino acid sequence indicated by ISYDGNT (SEQ ID NO: 2), a heavy chain CDR3 containing the amino acid sequence indicated by TSGWLLSLAEWG (SEQ ID NO: 3), a light chain CDR1 containing the amino acid sequence indicated by SEHSSSY (SEQ ID NO: 4), a light chain CDR2 containing the amino acid sequence indicated by LKSDGSH (SEQ ID NO: 5), and a light chain CDR3 containing the amino acid sequence indicated by GVAYSGGYV (SEQ ID NO: 6); (B) An anti-vanin-1 antibody comprising a heavy chain CDR1 containing the amino acid sequence indicated by GFTFSNYW (SEQ ID NO: 7), a heavy chain CDR2 containing the amino acid sequence indicated by INSDSSTM (SEQ ID NO: 8), a heavy chain CDR3 containing the amino acid sequence indicated by MTSGGLWG (SEQ ID NO: 9), a light chain CDR1 containing the amino acid sequence indicated by QSLLYSGNNNNY (SEQ ID NO: 10), a light chain CDR2 containing the amino acid sequence indicated by LAS, and a light chain CDR3 containing the amino acid sequence indicated by MQTFGIPRT (SEQ ID NO: 11); (C) An anti-vanin-1 antibody comprising a heavy chain CDR1 containing the amino acid sequence indicated by GFTFSNWY (SEQ ID NO: 12), a heavy chain CDR2 containing the amino acid sequence indicated by ISADSSDI (SEQ ID NO: 13), a heavy chain CDR3 containing the amino acid sequence indicated by ADISGSGI (SEQ ID NO: 14), a light chain CDR1 containing the amino acid sequence indicated by QSLLSSGNNKNY (SEQ ID NO: 15), a light chain CDR2 containing the amino acid sequence indicated by LAS, and a light chain CDR3 containing the amino acid sequence indicated by MQDYSVPLT (SEQ ID NO: 16);(D) An anti-vanin-1 antibody comprising a heavy chain CDR1 containing the amino acid sequence indicated by GFSLTSYS (SEQ ID NO: 17), a heavy chain CDR2 containing the amino acid sequence indicated by IWSDGSP (SEQ ID NO: 18), a heavy chain CDR3 containing the amino acid sequence indicated by ARDWGSLDV (SEQ ID NO: 19), a light chain CDR1 containing the amino acid sequence indicated by QSISRY (SEQ ID NO: 20), a light chain CDR2 containing the amino acid sequence indicated by YTN, and a light chain CDR3 containing the amino acid sequence indicated by QQYHSWPYT (SEQ ID NO: 21); (E) An anti-vanin-1 antibody comprising a heavy chain CDR1 containing the amino acid sequence indicated by GFTFSNDY (SEQ ID NO: 22), a heavy chain CDR2 containing the amino acid sequence indicated by ISGDSNYI (SEQ ID NO: 23), a heavy chain CDR3 containing the amino acid sequence indicated by ARHIAAYYFNL (SEQ ID NO: 24), a light chain CDR1 containing the amino acid sequence indicated by SVNNNF (SEQ ID NO: 25), a light chain CDR2 containing the amino acid sequence indicated by RTS, and a light chain CDR3 containing the amino acid sequence indicated by QQSSNDLT (SEQ ID NO: 26); (F) An anti-vanin-1 antibody comprising a heavy chain CDR1 containing the amino acid sequence indicated by GLTLSNSW (SEQ ID NO: 27), a heavy chain CDR2 containing the amino acid sequence indicated by INGDSRNI (SEQ ID NO: 28), a heavy chain CDR3 containing the amino acid sequence indicated by AASLDYYGLDI (SEQ ID NO: 29), a light chain CDR1 containing the amino acid sequence indicated by GLGNKY (SEQ ID NO: 30), a light chain CDR2 containing the amino acid sequence indicated by EDS, and a light chain CDR3 containing the amino acid sequence indicated by AIALGSGSGFHV (SEQ ID NO: 31); and (G) An anti-vanin-1 antibody comprising a heavy chain CDR1 containing the amino acid sequence indicated by GFTFSNSW (SEQ ID NO: 32), a heavy chain CDR2 containing the amino acid sequence indicated by INGDSTNI (SEQ ID NO: 33), a heavy chain CDR3 containing the amino acid sequence indicated by AAGPEYYSRNSYYMPFQY (SEQ ID NO: 34), a light chain CDR1 containing the amino acid sequence indicated by SDISVGRKS (SEQ ID NO: 35), a light chain CDR2 containing the amino acid sequence indicated by YYSDSDK (SEQ ID NO: 36), and a light chain CDR3 containing the amino acid sequence indicated by TIWHSGTWV (SEQ ID NO: 37).

[0017] The present invention provides a method for measuring Vanin-1 in a sample by latex agglutination, as well as reagents and kits used in the said method.

[0018] Figure 1 shows the results of Example 1. Figure 2 shows the results of Example 2.

[0019] 1. Definitions, etc. In this specification, Vanin-1 means Vascular noninflammatory molecule-1.

[0020] In this specification, Vanin-1 (antigen) is a protein registered in humans as National Center for Biotechnology Information (NCBI) Reference Sequence: NP_004657.2, and has the amino acid sequence shown in SEQ ID NO: 38: MTTQLPAYVAILLFYVSRASCQDTFTAAVYEHAAILPNATLTPVSREEALALMNRNLDILEGAITSAADQGAHIIVTPEDAIYGWNFNRDSLYPYLEDIPDPEVNWIPCNNRNRFGQTPVQERLSCLAKNNSIYVVANIGDKKPCDTSDPQCPPDGRYQYNTDVVFDSQGKLVARYHKQNLFMGENQFNVPKEPEIVTFNTTFGSFGIFTCFDILFHDPAVTLVKDFHVDTIVFPTAWMNVLPHLSAVEFHSAWAM GMRVNFLASNIHYPSKKMTGSGIYAPNSSRAFHYDMKTEEGKLLLSQLDSHPHSAVVNWTSYASSIEALSSGNKEFKGTVFFDEFTFVKLTGVAGNYTVCQKDLCCHLSYKMSENIPNEVYALGAFD GLHTVEGRYYLQICTLLKCKTTNLNTCGDSAETASTRFEMFSLSGTFGTQYVFPEVLLSENQLAPGEFQVSTDGRLFSLKPTSGPVLTVTLFGRLYEKDWASNASSGLTAQARIIMLIVIAPIVCSLSW

[0021] In this specification, the anti-Vanin-1 antibody may be a monoclonal antibody or a polyclonal antibody, but it is preferably a monoclonal antibody. The anti-Vanin-1 antibody can be any isotype, such as IgG, IgA, IgD, IgE, IgM, etc. The anti-Vanin-1 antibody may be a human antibody or a non-human antibody. Examples of non-human antibodies include, but are not limited to, mouse antibodies, rat antibodies, guinea pig antibodies, rabbit antibodies, etc. The anti-Vanin-1 antibody may be a chimeric antibody. The anti-Vanin-1 antibody may be a partially or fully humanized antibody.

[0022] In this specification, the antigen-binding fragment of the anti-Vanin-1 antibody is not particularly limited as long as it includes heavy chain CDR1-3 and light chain CDR1-3, for example, Fv, Fab, Fab', (Fab'). ２ Examples include scFv, scFv-Fc, diabody, triabody, tetrabody, and minibody.

[0023] In this specification, heavy chain CDR1-3 and light chain CDR1-3 are defined based on the IMGT method.

[0024] All patent and non-patent document disclosures cited herein are incorporated in their entirety by reference.

[0025] 2. Method for Measuring Vanin-1 in a Sample by Latex Agglutination Method In one embodiment, the method for measuring Vanin-1 in a sample by latex agglutination method (hereinafter simply referred to as "this measurement method") preferably uses a first latex particle carrying a first anti-Vanin-1 antibody or its antigen-binding fragment, and a second latex particle carrying a second anti-Vanin-1 antibody different from the first anti-Vanin-1 antibody or its antigen-binding fragment.

[0026] The specimen is not particularly limited as long as it may contain Vanin-1, but examples include urine, blood, serum, plasma, interstitial fluid, and ascites. Urine may be spontaneous urine, collected urine, catheterized urine, or urine obtained by puncture of the bladder or kidney.

[0027] The sample may be derived from a person with kidney disease, such as impaired renal function or kidney damage. Furthermore, this measurement method may also be a method for determining whether or not the person who collected the sample has kidney disease.

[0028] The first anti-Vanin-1 antibody and the second anti-Vanin-1 antibody are preferably selected from (A) to (G) below. (A) An anti-Vanin-1 antibody having a heavy chain CDR1 containing the amino acid sequence indicated by GFSITTTNYW (SEQ ID NO: 1), a heavy chain CDR2 containing the amino acid sequence indicated by ISYDGNT (SEQ ID NO: 2), a heavy chain CDR3 containing the amino acid sequence indicated by TSGWLLSLAEWG (SEQ ID NO: 3), a light chain CDR1 containing the amino acid sequence indicated by SEHSSSY (SEQ ID NO: 4), a light chain CDR2 containing the amino acid sequence indicated by LKSDGSH (SEQ ID NO: 5), and a light chain CDR3 containing the amino acid sequence indicated by GVAYSGGYV (SEQ ID NO: 6); (B) An anti-vanin-1 antibody comprising a heavy chain CDR1 containing the amino acid sequence indicated by GFTFSNYW (SEQ ID NO: 7), a heavy chain CDR2 containing the amino acid sequence indicated by INSDSSTM (SEQ ID NO: 8), a heavy chain CDR3 containing the amino acid sequence indicated by MTSGGLWG (SEQ ID NO: 9), a light chain CDR1 containing the amino acid sequence indicated by QSLLYSGNNNNY (SEQ ID NO: 10), a light chain CDR2 containing the amino acid sequence indicated by LAS, and a light chain CDR3 containing the amino acid sequence indicated by MQTFGIPRT (SEQ ID NO: 11); (C) An anti-vanin-1 antibody comprising a heavy chain CDR1 containing the amino acid sequence indicated by GFTFSNWY (SEQ ID NO: 12), a heavy chain CDR2 containing the amino acid sequence indicated by ISADSSDI (SEQ ID NO: 13), a heavy chain CDR3 containing the amino acid sequence indicated by ADISGSGI (SEQ ID NO: 14), a light chain CDR1 containing the amino acid sequence indicated by QSLLSSGNNKNY (SEQ ID NO: 15), a light chain CDR2 containing the amino acid sequence indicated by LAS, and a light chain CDR3 containing the amino acid sequence indicated by MQDYSVPLT (SEQ ID NO: 16);(D) An anti-vanin-1 antibody comprising a heavy chain CDR1 containing the amino acid sequence indicated by GFSLTSYS (SEQ ID NO: 17), a heavy chain CDR2 containing the amino acid sequence indicated by IWSDGSP (SEQ ID NO: 18), a heavy chain CDR3 containing the amino acid sequence indicated by ARDWGSLDV (SEQ ID NO: 19), a light chain CDR1 containing the amino acid sequence indicated by QSISRY (SEQ ID NO: 20), a light chain CDR2 containing the amino acid sequence indicated by YTN, and a light chain CDR3 containing the amino acid sequence indicated by QQYHSWPYT (SEQ ID NO: 21); (E) An anti-vanin-1 antibody comprising a heavy chain CDR1 containing the amino acid sequence indicated by GFTFSNDY (SEQ ID NO: 22), a heavy chain CDR2 containing the amino acid sequence indicated by ISGDSNYI (SEQ ID NO: 23), a heavy chain CDR3 containing the amino acid sequence indicated by ARHIAAYYFNL (SEQ ID NO: 24), a light chain CDR1 containing the amino acid sequence indicated by SVNNNF (SEQ ID NO: 25), a light chain CDR2 containing the amino acid sequence indicated by RTS, and a light chain CDR3 containing the amino acid sequence indicated by QQSSNDLT (SEQ ID NO: 26); (F) An anti-vanin-1 antibody comprising a heavy chain CDR1 containing the amino acid sequence indicated by GLTLSNSW (SEQ ID NO: 27), a heavy chain CDR2 containing the amino acid sequence indicated by INGDSRNI (SEQ ID NO: 28), a heavy chain CDR3 containing the amino acid sequence indicated by AASLDYYGLDI (SEQ ID NO: 29), a light chain CDR1 containing the amino acid sequence indicated by GLGNKY (SEQ ID NO: 30), a light chain CDR2 containing the amino acid sequence indicated by EDS, and a light chain CDR3 containing the amino acid sequence indicated by AIALGSGSGFHV (SEQ ID NO: 31); and (G) An anti-vanin-1 antibody comprising a heavy chain CDR1 containing the amino acid sequence indicated by GFTFSNSW (SEQ ID NO: 32), a heavy chain CDR2 containing the amino acid sequence indicated by INGDSTNI (SEQ ID NO: 33), a heavy chain CDR3 containing the amino acid sequence indicated by AAGPEYYSRNSYYMPFQY (SEQ ID NO: 34), a light chain CDR1 containing the amino acid sequence indicated by SDISVGRKS (SEQ ID NO: 35), a light chain CDR2 containing the amino acid sequence indicated by YYSDSDK (SEQ ID NO: 36), and a light chain CDR3 containing the amino acid sequence indicated by TIWHSGTWV (SEQ ID NO: 37).

[0029] The first anti-Vanin-1 antibody is preferably anti-Vanin-1 antibody (A). In this case, the second anti-Vanin-1 antibody is preferably selected from anti-Vanin-1 antibodies (B) to (G).

[0030] The second anti-Vanin-1 antibody is preferably anti-Vanin-1 antibody (B) or (C). In this case, the first anti-Vanin-1 antibody is preferably selected from anti-Vanin-1 antibodies (A) and (D) to (G).

[0031] The following combinations of the first and second anti-Vanin-1 antibodies are preferred: • Combination of anti-Vanin-1 antibodies (A) and (B) • Combination of anti-Vanin-1 antibodies (A) and (C)

[0032] Anti-Vanin-1 antibodies (A) to (G) or their antigen-binding fragments can be produced by combining known methods, for example, by a method comprising the following steps (P1) to (P6): (P1) obtaining cells that produce antibodies that bind to the Vanin-1 protein from antibody-producing cells of animals (e.g., guinea pigs, rats, rabbits) immunized with an antigen (full-length Vanin-1 protein) and optionally an adjuvant; (P2) obtaining an antibody variable region gene fragment from the cells obtained in step (P1); (P3) obtaining a gene expression unit from the antibody variable region gene fragment obtained in step (P2); (P4) introducing the gene expression unit obtained in step (P3) into cells to express antibodies that bind to the Vanin-1 protein; (P5) recovering the antibodies expressed in step (P4); and (P6) obtaining antibodies that bind to the Vanin-1 protein from the antibodies recovered in step (P5).

[0033] Step (P1) can be carried out in accordance with, for example, the method described in U.S. Patent Application Publication No. 2013 / 0029325 (ERIAA method) or the method described in the literature (Novel method for the high-throughput production of phosphorylation site-specific monoclonal antibodies, Scientific Reports, 2016, 6:25174) (FIXAA method).

[0034] Step (P2) can be carried out according to the method described in the literature (A rapid and efficient single-cell manipulation method for screening antigen-specific antibody-secreting cells from human peripheral blood, Nature Medicine 2009, 15(9), 1088-92) (ISAAC method) or the method described in the literature (Rapid production of antigen-specific monoclonal antibodies from a variety of animals, BMC Biology 2012, 10:80) (MAGrahd method).

[0035] Step (P3) can be carried out, for example, in accordance with the method described in U.S. Patent Application Publication No. 2013 / 0023009 (TS-jPCR method).

[0036] Step (P4) can be carried out by known gene transfer methods, such as calcium phosphate method, lipofection method, DEAE dextran method, electroporation method, microinjection method, etc. The cells into which the gene expression unit is introduced are not particularly limited as long as they can transiently express the antibody, and examples of mammalian cells include CHO cells, HEK293 cells, Expi293 cells, 293F cells, 293T cells, and 293FT cells.

[0037] Step (P6) can be carried out by selecting antibodies that specifically bind to the antigen using known screening methods, such as enzyme immunosorbent assay (ELISA), Western blotting, or immunohistochemical staining.

[0038] Furthermore, the anti-Vanin-1 antibody may be purified as needed by known methods, such as salting-out using ammonium sulfate, sodium sulfate, etc.; affinity chromatography using protein A, etc.; ion exchange chromatography using DEAE cellulose, etc.; gel filtration; or purification methods using His-tag, FLAG-tag, etc.

[0039] The first and second latex particles are not particularly limited, as long as they are latex particles that can be used in a normal latex agglutination method, and examples include synthetic resin particles. Examples of synthetic resins include styrene-based resins such as polystyrene, styrene-butadiene copolymer, and styrene-styrene sulfonate copolymer; vinyl-based resins such as polyvinyl chloride; olefin-based resins such as polypropylene; and acrylic-based resins such as poly(meth)acrylic acid and polymethyl (meth)acrylate. The first and second latex particles may be used individually or in combination of two or more types.

[0040] The lower limit of the average particle diameter of the first and second latex particles is, for example, 100 nm or more, preferably 150 nm or more, and more preferably 200 nm or more. The upper limit of the average particle diameter of the first and second latex particles is, for example, 500 nm or less, preferably 450 nm or less, and more preferably 400 nm or less. In one embodiment, the average particle diameter of the first and second latex particles is preferably 100 to 500 nm, each. The average particle diameter may be measured by, for example, electron microscopy (TEM, SEM), differential mobility analyzer (DMA method), optical microscopy, etc., but is usually measured by dynamic light scattering (DLS).

[0041] The first and second latex particles are usually used in the form of a latex particle liquid. The lower limit of the total concentration of the first and second latex particles in the latex particle liquid (or reaction solution) is, for example, 0.005% by mass or more, preferably 0.01% by mass or more, and more preferably 0.015% by mass or more. The upper limit of the total concentration is 0.5% by mass or less, preferably 0.45% by mass or less, and more preferably 0.4% by mass or less. In one embodiment, the total concentration is preferably 0.005 to 0.5% by mass.

[0042] The lower limit of the total concentration of the first anti-Vanin-1 antibody or its antigen-binding fragment and the second anti-Vanin-1 antibody or its antigen-binding fragment in the latex particle liquid (or reaction solution) is, for example, 0.001 mg / mL or more, preferably 0.002 mg / mL or more, and more preferably 0.003 mg / mL or more. The upper limit of the total concentration is, for example, 1 mg / mL or less, preferably 0.9 mg / mL or less, and more preferably 0.8 mg / mL or less. In one embodiment, the concentration is preferably 0.001 to 1 mg / mL.

[0043] In this measurement method, the measurement may be any of qualitative measurement, semi-quantitative measurement, and quantitative measurement. Qualitative measurement may be, for example, determining whether Vanin-1 is present in the sample. Semi-quantitative measurement may be, for example, determining the Vanin-1 concentration in the sample as "none", "low", "medium", "high", etc. Quantitative measurement may be, for example, measuring the Vanin-1 concentration in the sample.

[0044] In one embodiment, this measurement method preferably includes step A of reacting the sample with the first latex particles and the second latex particles (antigen-antibody reaction), and step B of measuring the aggregability of the reactant (antigen-antibody reactant) in step A.

[0045] In step A, the reaction method is not particularly limited, but it is preferable to mix the first reagent containing the sample and the second reagent containing the first and second latex particles.

[0046] The first reagent may be the sample itself, or may contain a diluent solution for the sample in addition to the sample. Examples of the diluent solution include buffer solutions, and specific examples thereof include Tris buffer, glycine buffer, phosphate buffer, borate buffer, Good buffer, etc. The first reagent may further contain additional additives, and in order to enhance the sensitivity of the reaction, water-soluble additives such as polyethylene glycol, carboxymethyl cellulose, methyl cellulose, hydroxyethyl cellulose, dextran, dextran sulfate, polyvinylpyrrolidone, polyglycosylethyl methacrylate, pullulan, elsinan and other water-soluble polymers may be contained. Further, the first reagent may contain, as additives, proteins such as casein, gelatin, BSA or their degradation products and denatured products; quaternary ammonium salts such as choline chloride, polyanions, chaotropic ions (Cl−, I−, SCN−, etc.), EDTA, amino acids, surfactants, etc. for the purpose of improving specificity, stability, etc. The concentration of the additive in the first reagent is, for example, 0.01 to 5% by mass, preferably 0.05 to 3% by mass.

[0047] The lower limit of the total concentration of the first and second latex particles in the second reagent is, for example, 0.01% by mass or more, preferably 0.02% by mass or more, more preferably 0.03% by mass or more. The upper limit of the total concentration is 1% by mass or less, preferably 0.7% by mass or less, more preferably 0.5% by mass or less. In one embodiment, the total concentration is preferably 0.01 to 1% by mass.

[0048] The lower limit of the total concentration of the first anti-Vanin-1 antibody or its antigen-binding fragment and the second anti-Vanin-1 antibody or its antigen-binding fragment in the second reagent is, for example, 0.002 mg / mL or more, preferably 0.004 mg / mL or more, more preferably 0.006 mg / mL or more. The upper limit of the total concentration is, for example, 2 mg / mL or less, preferably 1.5 mg / mL or less, more preferably 1 mg / mL or less. In one embodiment, the concentration is preferably 0.002 to 2 mg / mL.

[0049] The second reagent typically contains a solvent. Examples of solvents include buffer solutions, such as Tris buffer, glycine buffer, phosphate buffer, borate buffer, and Good's buffer. The second reagent may also contain further additives, and may contain proteins such as casein, gelatin, and BSA, or their degradation products or denatured products, for purposes such as improving specificity and stability. It may also contain sugars or sugar alcohols selected from sucrose, mannitol, sorbitol, xylitol, maltitol, raffinose, rhamnose, and combinations of two or more of these, as particle sedimentation inhibitors. The concentration of additives in the second reagent is, for example, 0.01 to 30% by mass, preferably 0.05 to 20% by mass, and more preferably 0.1 to 15% by mass.

[0050] The lower limit of the reaction temperature is preferably, for example, 25°C or higher, preferably 30°C or higher. The upper limit of the reaction temperature is preferably, for example, 45°C or lower, preferably 40°C or lower. In one embodiment, the reaction temperature is preferably 25 to 45°C. The reaction time may be, for example, 30 seconds to 15 minutes or 1 to 10 minutes.

[0051] In step B, there are no particular limitations on the method for measuring the cohesiveness of the reactants from step A, but for example, a method of measuring the change in turbidity is possible, and a method of measuring the change in absorbance at a wavelength of 570 nm is preferred.

[0052] Of the two time points for measuring the change in turbidity or the change in absorbance at a wavelength of 570 nm, the first time point is, for example, 5 seconds or more, preferably 7 seconds or more, and more preferably 10 seconds or more, after mixing the first reagent and the second reagent. Alternatively, the first time point may be, for example, 60 seconds or less, preferably 50 seconds or less, more preferably 40 seconds or less, and even more preferably 30 seconds or less, after mixing the first reagent and the second reagent. In one embodiment, the first time point is preferably 5 to 60 seconds after mixing the first reagent and the second reagent. The measured value at the first time point may be the average value of multiple measured values ​​within that range, and may be the average value of the measured value at 10 to 15 seconds (e.g., 13 seconds) after mixing the first reagent and the measured value at 25 to 30 seconds (e.g., 26 seconds) after mixing the first reagent and the second reagent.

[0053] Of the two time points for measuring the change in turbidity or the change in absorbance at a wavelength of 570 nm, the second time point is, for example, 240 seconds or more, preferably 250 seconds or more, more preferably 260 seconds or more, even more preferably 270 seconds or more, and even more preferably 280 seconds or more, after mixing the first reagent and the second reagent. Alternatively, the second time point may be, for example, 320 seconds or less, preferably 310 seconds or less, more preferably 300 seconds or less, and even more preferably 290 seconds or less, after mixing the first reagent and the second reagent. In one embodiment, the second time point is preferably 240 to 320 seconds after mixing the first reagent and the second reagent. The measured value at the second time point may be the average value of multiple measured values ​​within that range, and may be the average value of the measured value at 280 to 290 seconds (e.g., 288 seconds) after mixing the first reagent and the measured value at 310 to 320 seconds (e.g., 311 seconds) after mixing the first reagent and the second reagent.

[0054] This indicates that the greater the absolute value (ΔmAbs) of the difference between the measured values ​​at the first and second time points, such as the change in turbidity or the change in absorbance at a wavelength of 570 nm, the more sensitive the measurement can be.

[0055] 3. Reagents or kits for measuring Vanin-1 in a sample by latex agglutination In one embodiment, the reagent or kit for measuring Vanin-1 protein in a sample by latex agglutination preferably contains the first and second antibodies or their antigen-binding fragments described in 2 above. The first and second antibodies or their antigen-binding fragments may be used as reagents alone, or a composition including pharmaceutically acceptable excipients or carriers and / or additives may be used as the reagent. Examples of the excipients or carriers include starch, lactose, crystalline cellulose, sorbitol, calcium hydrogen phosphate, water, ethanol, (poly)ethylene glycol, (poly)propylene glycol, glycerol, and vegetable oil. These can be used individually or in combination of two or more.

[0056] The first and second antibodies or their antigen-binding fragments may be included in the kit in the form of the reagent.

[0057] The kit may contain the reagents necessary for the latex agglutination method (for example, the latex particles, buffer solution, and diluent described in item 2 above). Two or more reagents may be sealed in the same container or in separate containers, and these containers may be housed in a single package. In addition to the reagents, the kit may also contain equipment, instructions for use, etc.

[0058] The present invention will be described more specifically below based on examples, but the present invention is not limited to these examples.

[0059] [Antibody Production] (Acquisition of antibody-producing cells by animal immunization) As the first immunization, 100 μg of recombinant Vanin-1 protein suspended in PBS was mixed with the adjuvant TiterMAX Gold (Funakoshi Co., Ltd.) and administered intramuscularly to the left and right gluteal muscles of guinea pigs. 21 days after the first immunization, 100 μg of recombinant Vanin-1 protein suspended in PBS was mixed with TiterMAX Gold and administered as an additional immunization subcutaneously to the dorsal base of the guinea pigs' limbs. Furthermore, 21 days after the additional immunization, 100 μg of recombinant Vanin-1 protein suspended in PBS was administered again as an additional immunization intramuscularly to the left and right gluteal muscles of the guinea pigs. 7 days after the second additional immunization, the two guinea pigs were anesthetized, had their blood totaled and euthanized, and their lumbar lymph nodes were removed.

[0060] (Sorting of plasma cells producing anti-Vanin-1 antibody) This was carried out in accordance with the method (ERIAA method) described in "Fluorescent probe for plasma cell identification and isolation and method for identifying or isolating plasma cells using the probe" (U.S. Patent Application Publication 2013 / 0029325).

[0061] Cells obtained from excised lumbar lymph nodes were fixed in formaldehyde PBS solution on ice for 10 minutes. The fixed cells were stained with Dylight488-labeled Vanin-1 protein, Dylight650-labeled anti-guinea pig IgG antibody, and DAPI (4',6-diamidino-2-phenylindole). Plasma cells showing strong positivity for both Vanin-1 protein and anti-guinea pig IgG antibody were sorted by flow cytometry.

[0062] (Synthesis of antibody variable region gene fragments) For each cell obtained by sorting, mRNA extraction, cDNA synthesis, and amplification of antibody variable region gene fragments were performed according to the method of Kurosawa et al. (MAGrahd method) (Rapid production of antigen-specific monoclonal antibodies from a variety of animals, BMC Biology 2012, 10:80).

[0063] (Preparation of antibody gene expression units) Antibody gene expression units were prepared from amplified antibody variable region gene fragments according to the method (TS-jPCR method) described in "Specific method for producing linked DNA fragments containing target gene-derived sequences" (U.S. Patent Application Publication No. 2013 / 0023009).

[0064] (Transient antibody expression in 293FT cells) The prepared antibody gene expression unit, FuGENE HD Transfection Reagent (trademark), and OptiPRO (trademark) were mixed in a 1:1:100 liquid-volume ratio and allowed to stand at room temperature for 20 minutes. The antibody gene expression unit was then introduced into 293FT cells suspended in DMEM medium containing 10% (w / v) FBS. The 293FT cells into which the antibody gene expression unit had been introduced were seeded in a 24-well plate and incubated at 37°C in 5% (v / v) CO2. ２ After incubation in the environment for 3 days, the culture supernatant was collected. Subsequent screening was performed using antibodies released in the culture supernatant.

[0065] (Antibody screening by ELISA) Screening was performed by evaluating the binding activity of each antibody to the Vanin-1 protein by ELISA. For the ELISA, Vanin-1 protein was immobilized on the bottom of a 96-well plate at a concentration of 10 ng / well, blocked with 1% (w / v) BSA-TBS-T, and then 100 μL of the culture supernatant of 293FT cells transiently expressing the antibody was added. The antigen-antibody reaction was carried out at room temperature for 1 hour. Guinea pig antibodies bound to the antigen were detected using alkaline phosphatase-labeled goat anti-guinea pig antibodies, and the absorbance at 405 nm was measured using a microplate reader.

[0066] (Preparation of antibody expression plasmids) Based on the results of ELISA evaluation, DNA encoding the sequence containing the CDR of the antibody was obtained from antibody clones that showed good reactivity. Antibody expression plasmids containing guinea pig-derived heavy chain and light chain constant regions were prepared using the Mammalian PowerExpress System (trademark) (MPH-102 and MPL-202, Toyobo Co., Ltd.) in accordance with the accompanying instructions.

[0067] (Transient Expression and Purification of Antibodies in ExpiCHO-S® Cells) Antibodies were produced by introducing the prepared antibody expression plasmids into ExpiCHO-S® cells. For gene transfer, ExpiCHO-S® Expression Medium (Thermo Fisher Scientific) and ExpiFectamine® CHO Transfection Kit (Thermo Fisher Scientific) were used. Gene transfer was performed by mixing 20 μg of each prepared antibody expression plasmid with 920 μL of OptiPRO® SFM and 80 μL of ExpiFectamine® CHO Reagent, allowing it to stand for 5 minutes, and then adding it to 25 mL of culture medium containing ExpiCHO-S® cells. 37°C, 5% (v / v) CO2 ２After 5 days of shaking culture at 110 rpm, the culture supernatant was collected. Next, the culture supernatant was passed through a HiTrap Protein A HP column (Cytiva) using the NGC™ Chromatography System (Bio-Rad) to adsorb the antibody. The column was washed with washing buffer (20 mM phosphate buffer, pH 7.4), and then eluted with elution buffer (0.1 M citrate-NaOH, pH 3.0) to obtain purified antibody. The obtained purified antibody was evaluated using a PD-10 column (Cytiva) with Tris-buffered saline (pH 7.4) instead of Tris buffer.

[0068] Table 1 shows the amino acid sequences (based on IMTG method) of the heavy chain CDR1-3 and light chain CDR1-3 of seven antibody clones that specifically bound to the Vanin-1 protein from among the acquired antibody clones.

[0069]

[0070] As a control, we used the commercially available antibody solution Monoclonal Antibody to Vanin-1 (VNN1) MAC598Hu22 (CLOUD-CLONE CORP) (hereinafter abbreviated as "M").

[0071] [Example 1] Preparation of anti-Vanin-1 antibody-sensitized latex particles (Second Reagent) 1 mL of a solution containing 0.5% by mass latex particles with an average particle size of 0.3 μm (a solution prepared by diluting 50 μL of Fujikura Chemicals FK-S300D with 950 μL of 10 mM HEPES (pH 7.0)) was added to 0.4 mL of anti-Vanin-1 antibody solution (PBS, pH 8.0) 1, 2, or 3 from Table 2, adjusted to 1 mg / mL. The mixture was stirred at room temperature for 2 hours, then centrifuged and the supernatant was removed. 1 mL of 1.0% (w / v) BSA / PBS (pH 7.4) was added to resuspend the mixture, and after sonication, the mixture was stirred at 4°C for at least 1 hour. After stirring, the supernatant was removed by centrifugation, 1 mL of 20 mM Tris-HCl (pH 8.0) was added and the mixture was resuspended. The mixture was then sonicated and diluted with 20 mM Tris-HCl (pH 8.0) to a concentration of 0.1% by mass to obtain the second reagent.

[0072]

[0073] - Reagent 1: A 20 mM Tris-HCl buffer (pH 8.0) containing 0.1% (w / v) BSA was prepared and used as Reagent 1.

[0074] • Recombinant Vanin-1 (VNN1) RPC598Hu04 (vanin-1 Gln22-Gly491 with N-terminal His Tag) (CLOUD-CLONE CORP) was used as the sample antigen. The antigen was diluted with 100 mM Tris-HCl (pH 8.0) containing 0.1% (w / v) BSA and used for measurement.

[0075] The antigen was measured using a Bioliss 30i automated analyzer (Tokyo Boeki Medisys Co., Ltd.) by combining the first and second reagents. Specifically, 150 μL of the first reagent and 6 μL of the sample were added to the cell and mixed uniformly, then incubated at 37°C for 5 minutes. After that, 50 μL of the second reagent was added and mixed uniformly, and the turbidity change was measured at a main wavelength of 570 nm for 5 minutes. The absolute value (ΔmAbs) of the difference between the average absorbance at 13 seconds and 26 seconds after adding the second reagent, and the average absorbance at 288 seconds and 311 seconds was calculated and evaluated. A higher ΔmAbs indicates that measurement is possible with higher sensitivity.

[0076] The results are shown in Figure 1. As is clear from Figure 1, anti-Vanin-1 antibody solutions 1 and 2 can measure the antigen with significantly higher sensitivity than anti-Vanin-1 antibody solution 3.

[0077] Example 2 Preparation of anti-Vanin-1 antibody-sensitized latex particles (Second Reagent) 1 mL of a solution containing 0.5% by mass latex particles with an average particle size of 0.4 μm (a solution prepared by diluting 50 μL of Fujikura Chemicals FK-S400D with 950 μL of 10 mM HEPES (pH 7.0)) was added to 0.3 mL of anti-Vanin-1 antibody solution (PBS, pH 8.0) 1, 2, or 3 from Table 3, adjusted to 1 mg / mL. The mixture was stirred at room temperature for 2 hours, then centrifuged and the supernatant was removed. 1 mL of 1.0% (w / v) BSA / PBS (pH 7.4) was added to resuspend the mixture, and after sonication, the mixture was stirred at 4°C for at least 1 hour. After stirring, the supernatant was removed by centrifugation, 1 mL of 20 mM Tris-HCl (pH 8.0) was added and the mixture was resuspended. The mixture was then sonicated and diluted with 20 mM Tris-HCl (pH 8.0) to a concentration of 0.05% by mass to obtain the second reagent.

[0078]

[0079] - Reagent 1: A 20 mM Tris-HCl buffer (pH 8.0) containing 0.1% BSA was prepared and used as Reagent 1.

[0080] • Recombinant Vanin-1 (VNN1) RPC598Hu04 (vanin-1 Gln22-Gly491 with N-terminal His Tag) (CLOUD-CLONE CORP) was used as the sample antigen. The antigen was diluted with 100 mM Tris-HCl (pH 8.0) containing 0.1% (w / v) BSA and used for measurement.

[0081] The antigen was measured using a Bioliss 30i automated analyzer (Tokyo Boeki Medisys) by combining the first and second reagents. Specifically, 150 μL of the first reagent and 6 μL of the sample were added to a cell and mixed uniformly, then incubated at 37°C for 5 minutes. After that, 50 μL of the second reagent was added and mixed uniformly, and the turbidity change was measured at a main wavelength of 570 nm for 5 minutes. The absolute value (ΔmAbs) of the difference between the average absorbance at 13 seconds and 26 seconds after adding the second reagent, and the average absorbance at 288 seconds and 311 seconds was calculated and evaluated. A higher ΔmAbs indicates that measurement is possible with higher sensitivity.

[0082] The results are shown in Figure 2. As is clear from Figure 2, anti-Vanin-1 antibody solution 1 can measure the antigen with significantly higher sensitivity than anti-Vanin-1 antibody solutions 2 and 3.

Claims

1. A method for measuring Vanin-1 in a sample by latex agglutination, comprising: a first latex particle carrying a first anti-Vanin-1 antibody or its antigen-binding fragment selected from (A) to (G) below; and a second latex particle carrying a second anti-Vanin-1 antibody or its antigen-binding fragment selected from (A) to (G) below and different from the first anti-Vanin-1 antibody: (A) An anti-vanin-1 antibody comprising a heavy chain CDR1 containing the amino acid sequence indicated by GFSITTTNYW (SEQ ID NO: 1), a heavy chain CDR2 containing the amino acid sequence indicated by ISYDGNT (SEQ ID NO: 2), a heavy chain CDR3 containing the amino acid sequence indicated by TSGWLLSLAEWG (SEQ ID NO: 3), a light chain CDR1 containing the amino acid sequence indicated by SEHSSSY (SEQ ID NO: 4), a light chain CDR2 containing the amino acid sequence indicated by LKSDGSH (SEQ ID NO: 5), and a light chain CDR3 containing the amino acid sequence indicated by GVAYSGGYV (SEQ ID NO: 6); (B) An anti-vanin-1 antibody comprising a heavy chain CDR1 containing the amino acid sequence indicated by GFTFSNYW (SEQ ID NO: 7), a heavy chain CDR2 containing the amino acid sequence indicated by INSDSSTM (SEQ ID NO: 8), a heavy chain CDR3 containing the amino acid sequence indicated by MTSGGLWG (SEQ ID NO: 9), a light chain CDR1 containing the amino acid sequence indicated by QSLLYSGNNNNY (SEQ ID NO: 10), a light chain CDR2 containing the amino acid sequence indicated by LAS, and a light chain CDR3 containing the amino acid sequence indicated by MQTFGIPRT (SEQ ID NO: 11); (C) An anti-vanin-1 antibody comprising a heavy chain CDR1 containing the amino acid sequence indicated by GFTFSNWY (SEQ ID NO: 12), a heavy chain CDR2 containing the amino acid sequence indicated by ISADSSDI (SEQ ID NO: 13), a heavy chain CDR3 containing the amino acid sequence indicated by ADISGSGI (SEQ ID NO: 14), a light chain CDR1 containing the amino acid sequence indicated by QSLLSSGNNKNY (SEQ ID NO: 15), a light chain CDR2 containing the amino acid sequence indicated by LAS, and a light chain CDR3 containing the amino acid sequence indicated by MQDYSVPLT (SEQ ID NO: 16);(D) An anti-vanin-1 antibody comprising a heavy chain CDR1 containing the amino acid sequence indicated by GFSLTSYS (SEQ ID NO: 17), a heavy chain CDR2 containing the amino acid sequence indicated by IWSDGSP (SEQ ID NO: 18), a heavy chain CDR3 containing the amino acid sequence indicated by ARDWGSLDV (SEQ ID NO: 19), a light chain CDR1 containing the amino acid sequence indicated by QSISRY (SEQ ID NO: 20), a light chain CDR2 containing the amino acid sequence indicated by YTN, and a light chain CDR3 containing the amino acid sequence indicated by QQYHSWPYT (SEQ ID NO: 21); (E) An anti-vanin-1 antibody comprising a heavy chain CDR1 containing the amino acid sequence indicated by GFTFSNDY (SEQ ID NO: 22), a heavy chain CDR2 containing the amino acid sequence indicated by ISGDSNYI (SEQ ID NO: 23), a heavy chain CDR3 containing the amino acid sequence indicated by ARHIAAYYFNL (SEQ ID NO: 24), a light chain CDR1 containing the amino acid sequence indicated by SVNNNF (SEQ ID NO: 25), a light chain CDR2 containing the amino acid sequence indicated by RTS, and a light chain CDR3 containing the amino acid sequence indicated by QQSSNDLT (SEQ ID NO: 26); (F) An anti-vanin-1 antibody comprising a heavy chain CDR1 containing the amino acid sequence indicated by GLTLSNSW (SEQ ID NO: 27), a heavy chain CDR2 containing the amino acid sequence indicated by INGDSRNI (SEQ ID NO: 28), a heavy chain CDR3 containing the amino acid sequence indicated by AASLDYYGLDI (SEQ ID NO: 29), a light chain CDR1 containing the amino acid sequence indicated by GLGNKY (SEQ ID NO: 30), a light chain CDR2 containing the amino acid sequence indicated by EDS, and a light chain CDR3 containing the amino acid sequence indicated by AIALGSGSGFHV (SEQ ID NO: 31); and (G) An anti-vanin-1 antibody comprising a heavy chain CDR1 containing the amino acid sequence indicated by GFTFSNSW (SEQ ID NO: 32), a heavy chain CDR2 containing the amino acid sequence indicated by INGDSTNI (SEQ ID NO: 33), a heavy chain CDR3 containing the amino acid sequence indicated by AAGPEYYSRNSYYMPFQY (SEQ ID NO: 34), a light chain CDR1 containing the amino acid sequence indicated by SDISVGRKS (SEQ ID NO: 35), a light chain CDR2 containing the amino acid sequence indicated by YYSDSDK (SEQ ID NO: 36), and a light chain CDR3 containing the amino acid sequence indicated by TIWHSGTWV (SEQ ID NO: 37).

2. The method according to claim 1, wherein the first anti-Vanin-1 antibody is anti-Vanin-1 antibody (A).

3. The method according to claim 1 or 2, wherein the second anti-Vanin-1 antibody is anti-Vanin-1 antibody (B) or (C).

4. The method according to claim 1 or 2, wherein the average particle diameter of the first and second latex particles is 100 to 500 nm, respectively.

5. The method according to claim 1 or 2, wherein a latex particle liquid is used in which the total concentration of the first and second latex particles is 0.005 to 0.5% by mass.

6. The method according to claim 1 or 2, wherein the measurement is a qualitative measurement, a semi-quantitative measurement, or a quantitative measurement.

7. The method according to claim 1 or 2, wherein the specimen is selected from urine, blood, serum, plasma, and interstitial fluid.

8. The method according to claim 7, wherein when the measured value obtained based on the measurement of the sample is greater than or equal to a reference value, it suggests that the subject from whom the sample was collected has a kidney disease.

9. Reagents or kits for measuring Vanin-1 in a sample by latex agglutination, comprising a first anti-Vanin-1 antibody or its antigen-binding fragment selected from (A) to (G) below, and a second anti-Vanin-1 antibody or its antigen-binding fragment selected from (A) to (G) below and different from the first anti-Vanin-1 antibody: (A) An anti-Vanin-1 antibody having a heavy chain CDR1 containing the amino acid sequence indicated by GFSITTTNYW (SEQ ID NO: 1), a heavy chain CDR2 containing the amino acid sequence indicated by ISYDGNT (SEQ ID NO: 2), a heavy chain CDR3 containing the amino acid sequence indicated by TSGWLLSLAEWG (SEQ ID NO: 3), a light chain CDR1 containing the amino acid sequence indicated by SEHSSSY (SEQ ID NO: 4), a light chain CDR2 containing the amino acid sequence indicated by LKSDGSH (SEQ ID NO: 5), and a light chain CDR3 containing the amino acid sequence indicated by GVAYSGGYV (SEQ ID NO: 6); (B) An anti-vanin-1 antibody comprising a heavy chain CDR1 containing the amino acid sequence indicated by GFTFSNYW (SEQ ID NO: 7), a heavy chain CDR2 containing the amino acid sequence indicated by INSDSSTM (SEQ ID NO: 8), a heavy chain CDR3 containing the amino acid sequence indicated by MTSGGLWG (SEQ ID NO: 9), a light chain CDR1 containing the amino acid sequence indicated by QSLLYSGNNNNY (SEQ ID NO: 10), a light chain CDR2 containing the amino acid sequence indicated by LAS, and a light chain CDR3 containing the amino acid sequence indicated by MQTFGIPRT (SEQ ID NO: 11); (C) An anti-vanin-1 antibody comprising a heavy chain CDR1 containing the amino acid sequence indicated by GFTFSNWY (SEQ ID NO: 12), a heavy chain CDR2 containing the amino acid sequence indicated by ISADSSDI (SEQ ID NO: 13), a heavy chain CDR3 containing the amino acid sequence indicated by ADISGSGI (SEQ ID NO: 14), a light chain CDR1 containing the amino acid sequence indicated by QSLLSSGNNKNY (SEQ ID NO: 15), a light chain CDR2 containing the amino acid sequence indicated by LAS, and a light chain CDR3 containing the amino acid sequence indicated by MQDYSVPLT (SEQ ID NO: 16);(D) An anti-vanin-1 antibody comprising a heavy chain CDR1 containing the amino acid sequence indicated by GFSLTSYS (SEQ ID NO: 17), a heavy chain CDR2 containing the amino acid sequence indicated by IWSDGSP (SEQ ID NO: 18), a heavy chain CDR3 containing the amino acid sequence indicated by ARDWGSLDV (SEQ ID NO: 19), a light chain CDR1 containing the amino acid sequence indicated by QSISRY (SEQ ID NO: 20), a light chain CDR2 containing the amino acid sequence indicated by YTN, and a light chain CDR3 containing the amino acid sequence indicated by QQYHSWPYT (SEQ ID NO: 21); (E) An anti-vanin-1 antibody comprising a heavy chain CDR1 containing the amino acid sequence indicated by GFTFSNDY (SEQ ID NO: 22), a heavy chain CDR2 containing the amino acid sequence indicated by ISGDSNYI (SEQ ID NO: 23), a heavy chain CDR3 containing the amino acid sequence indicated by ARHIAAYYFNL (SEQ ID NO: 24), a light chain CDR1 containing the amino acid sequence indicated by SVNNNF (SEQ ID NO: 25), a light chain CDR2 containing the amino acid sequence indicated by RTS, and a light chain CDR3 containing the amino acid sequence indicated by QQSSNDLT (SEQ ID NO: 26); (F) An anti-vanin-1 antibody comprising a heavy chain CDR1 containing the amino acid sequence indicated by GLTLSNSW (SEQ ID NO: 27), a heavy chain CDR2 containing the amino acid sequence indicated by INGDSRNI (SEQ ID NO: 28), a heavy chain CDR3 containing the amino acid sequence indicated by AASLDYYGLDI (SEQ ID NO: 29), a light chain CDR1 containing the amino acid sequence indicated by GLGNKY (SEQ ID NO: 30), a light chain CDR2 containing the amino acid sequence indicated by EDS, and a light chain CDR3 containing the amino acid sequence indicated by AIALGSGSGFHV (SEQ ID NO: 31); and (G) An anti-vanin-1 antibody comprising a heavy chain CDR1 containing the amino acid sequence indicated by GFTFSNSW (SEQ ID NO: 32), a heavy chain CDR2 containing the amino acid sequence indicated by INGDSTNI (SEQ ID NO: 33), a heavy chain CDR3 containing the amino acid sequence indicated by AAGPEYYSRNSYYMPFQY (SEQ ID NO: 34), a light chain CDR1 containing the amino acid sequence indicated by SDISVGRKS (SEQ ID NO: 35), a light chain CDR2 containing the amino acid sequence indicated by YYSDSDK (SEQ ID NO: 36), and a light chain CDR3 containing the amino acid sequence indicated by TIWHSGTWV (SEQ ID NO: 37).

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