CN-121342976-B - Anti-KLHL 11 antibody and application thereof

Abstract

The invention relates to an anti-KLHL 11 antibody and application thereof, belonging to the technical field of antibodies, wherein the anti-KLHL 11 antibody comprises VHH, and the VHH comprises CDR1, CDR2 and CDR3 in an amino acid sequence shown as SEQ ID NO. 2. The invention develops the high-specificity and high-affinity anti-KLHL 11 antibody for the first time, can be used as a positive reference for detecting the anti-KLHL 11 autoantibody kit, solves the problems of development and quality control of the diagnosis kit caused by difficult acquisition of positive serum and complex components in the prior art, and is particularly suitable for the diagnosis kit of the autoimmune diseases (such as autoimmune encephalitis) of the nervous system.

Inventors

• PENG LISHENG
• XU CANCAN
• HOU LI
• ZHU JINXIN
• Mai Xuexia
• XIE ZHIDA
• LIANG YUNXIAN

Assignees

• 广州敏特生物技术有限公司

Dates

Publication Date

20260512

Application Date

20251104

Claims (2)

1. 1. An anti-KLHL 11 antibody, which is a humanized chimeric antibody comprising a VHH comprising the amino acid sequence as set forth in SEQ ID No. 2, wherein the VHH of the humanized chimeric antibody is linked to a human IgG1 Fc fragment.
2. 2. A kit for detecting an anti-KLHL 11 autoantibody comprising a positive reference, wherein the positive reference is the anti-KLHL 11 antibody of claim 1.

Description

Anti-KLHL 11 antibody and application thereof Technical Field The invention belongs to the field of antibodies, and particularly relates to an anti-KLHL 11 antibody and application thereof. Background The autoimmune diseases of nervous system are diseases caused by injury such as inflammation caused by autoimmune molecules and immune cells recognizing the self components (autoantigen) of tissue cells of nervous system, and can occur in central nervous system, peripheral nervous system and nerve-muscle joints, including autoimmune encephalitis (autoimmune encephalitis, AE), central demyelinating diseases, autoimmune peripheral neuropathy, etc. Among them, AE is most commonly seen in clinical manifestations of acute or subacute onset (< 3 months), with one or more neurological and psychiatric symptoms or clinical syndromes: 1) marginal systemic symptoms: hypomnesis, seizures, abnormal mental behavior, 2) encephalitis syndrome: clinical manifestations of diffuse or multifocal brain lesions, 3) basal ganglia and/or inter/hypothalamic involvement, 4) psychotic disorders, and psycho-psychological specialty considered non-conforming to non-organic diseases. Mainly affects people in middle-aged and young, and has high mortality and disability rate. Autoantibodies against KLHL11 (Kelch-like protein 11) are biomarkers of great interest in recent years in the study of neurological diseases, and are of great importance in particular in the diagnosis of autoimmune neurological diseases. Is a biomarker which is of great interest in the research of nervous system diseases in recent years, and has important significance in the diagnosis of autoimmune nervous diseases in particular. Currently, there are detection kits directed against KLHL11 (Kelch-like protein 11) autoantibodies. Whether a detection kit prepared by using a plurality of methods such as a cell-based immunofluorescence method, an immunospot method, a chemiluminescence method, a colloidal gold method or an ELISA method is used, a plurality of difficulties exist in the product design and development stage, and the products have no national standard, industry standard and the like which are on the market as references, and enterprises can only use positive serum and negative serum to establish enterprise references for the research of product performance verification, quality control and the like, but due to complex serum components, the morbidity of the diseases is low, the positive serum is less in quantity and is not easy to collect, and the early research and the long-term quality control of the products cannot be satisfied. Therefore, there is a need in the art to develop humanized chimeric antibodies that bind KLHL11 to meet the requirements of positive references for diagnostic kits Disclosure of Invention In order to overcome the disadvantages of the prior art, the present invention aims to provide an anti-KLHL 11 antibody and application thereof, wherein the antibody has strong specificity and high sensitivity, can meet the requirements of positive references of diagnostic kits, is easy to store and reform, and has the capability of recognizing a target antigen KLHL 11. In a first aspect, the invention provides an anti-KLHL 11 antibody comprising a VHH comprising CDR1, CDR2 and CDR3 of the amino acid sequence shown in SEQ ID NO. 2. Alternatively, the CDRs 1-3 are determined according to the Kabat numbering system, abM numbering system, IMGT numbering system, chothia numbering system or Contact numbering system. Alternatively, the amino acid sequence of the CDR1 is shown as SEQ ID NO. 3, the amino acid sequence of the CDR2 is shown as SEQ ID NO. 4, and the amino acid sequence of the CDR3 is shown as SEQ ID NO. 5. Optionally, the VHH comprises an amino acid sequence with more than 90% homology, wherein any one or more amino acids in the amino acid sequence shown in SEQ ID NO. 2 are substituted, deleted and/or added with one or more amino acids and/or subjected to terminal modification. Alternatively, the VHH comprises an amino acid sequence as shown in SEQ ID NO. 2. Alternatively, the anti-KLHL 11 antibody is a humanized chimeric antibody. Alternatively, the VHH is linked to a human IgG1 Fc fragment. In a second aspect, the invention provides the use of an anti-KLHL 11 antibody as described in the first aspect for the preparation of a kit for detecting anti-KLHL 11 autoantibodies. Optionally, the method for detecting the anti-KLHL 11 autoantibody is selected from at least one of CBA, immunoblotting, membrane strip method, ELISA, chemiluminescence, radioimmunoassay, liquid chip method, lateral chromatography, electrochemistry and flow cell. In a third aspect, the invention provides a kit for detecting an anti-KLHL 11 autoantibody, comprising a positive reference, wherein the positive reference is the anti-KLHL 11 antibody. Alternatively, the kit is used for autoimmune diseases of the nervous system, such as, for example, autoimmune encephalitis. Compared w