A VHH antibody against human FcRn and its application

Abstract

This invention belongs to the field of biology and discloses a VHH antibody against human FcRn and its applications. The complementarity-determining regions (CDR1-CDR3) of the VHH antibody are shown in SEQ ID NO. 1-9. Some examples of the anti-human FcRn VHH antibodies of this invention can specifically bind to human FcRn; they can replace traditional antibodies and be used in the treatment and diagnosis of autoimmune diseases; the fused Fc fragment targets and binds to the FcRn receptor, effectively reducing the half-life of IgG in the blood while enhancing antibody targeting. Some examples of the anti-human FcRn VHH antibodies of this invention, by fusing the Fc fragment, can increase their affinity for the FcRn receptor, effectively reducing the half-life of IgG in autoimmune diseases, while also mitigating ADCC and CDC effects.

Description

Technical Field

[0001] This invention belongs to the field of biology, specifically relating to a VHH antibody against human FcRn and its application. Background Technology

[0002] The neonatal Fc receptor (FcRn) has a molecular structure similar to MHC class I molecules, consisting of a heavy chain (containing α1-α2-α3 domains and a transmembrane region) and a non-covalently bound β2-MG. FcRn is an atypical FcγR, acting only on IgG and not on other immunoglobulins. α1 binds to IgG, while α2-α3 bind to albumin; these two binding sites are independent and do not interfere with each other. FcRn is expressed in various cells and organs, including epidermal cells, endothelial cells, APCs, hematopoietic stem cells, small intestine, kidney, lung, and central nervous system, making it a multifunctional receptor capable of performing various functions. Under acidic conditions (pH 6.0-6.5), FcRn has a high affinity for the Fc fragment. IgG molecules are engulfed intracellularly via endocytosis and fuse with acidic granulosomes to form an acidic nucleosome environment. Unbound IgG and other proteins are sorted and enter lysosomes for degradation. At physiological pH (7.4), the binding ability of the two is actually weaker. Unbound IgG is released back into the extracellular space through exocytosis, thus protecting IgG and maintaining its half-life in a cycle.

[0003] Antibodies, also called immunoglobulins (Ig), are proteins that specifically bind to antigens. Antibodies consist of four polypeptide chains: two heavy chains (H chains, 50kD) and two light chains (L chains, 23kD), linked by disulfide bonds. The hydroxyl terminus of the polypeptide chain contains relatively stable amino acids with no significant differences in number or order; this region is called the invariant or stable region, or C region, and occupies half of the L chain and three-quarters of the H chain. The amino terminus contains a region where the sequence of different amino acids varies; this region is called the variable region, or V region. The highly variable nature of the variable region determines the diversity of antibodies and also determines that antibodies bind only to specific antigens. Humans have five different classes of antibodies: IgA (including subclasses IgA1 and IgA2), IgD, IgE, IgG (including subclasses IgG1, IgG2, IgG3, and IgG4), and IgM. IgG is the most prevalent type of immunoglobulin in humans and is commonly used in treatment. In autoimmune diseases, the body's immune system mistakenly identifies its own tissues or organs as foreign antigens, triggering an immune response. Abnormally activated B lymphocytes proliferate and differentiate into plasma cells, producing excessive immunoglobulins, including IgG. Excess IgG can bind to antigens in the body's own tissues or organs, forming immune complexes. These immune complexes deposit in tissues, activating the complement system, causing inflammation, and leading to tissue damage. IgG can also directly kill the body's own tissue cells through antibody-dependent cell-mediated cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC), exacerbating tissue damage. Therefore, effectively reducing IgG levels in autoimmune diseases is crucial.

[0004] Unlike conventional antibody molecules composed of four polypeptide chains (heavy and light chains), single-domain antibodies (sdAbs) are a class of antibodies that lack the antibody light chain and only possess the variable domain of the heavy chain. They are called VHHs (Variable Domain of Heavy Chain of Heavy Chain antibody) and, due to their small molecular weight, are also known as nanobodies. Although single-domain antibodies have a simple structure, they can still achieve affinity for specific antigens comparable to or even higher than that of traditional antibodies. Compared to traditional antibodies, single-domain antibodies have advantages such as small molecular weight, high stability, and ease of recombinant expression.

[0005] Autoimmune diseases encompass illnesses that occur when the body's immune system attacks its own normal tissues, organs, or other components due to an unexplained immune system abnormality. These autoimmune diseases are systemic illnesses that can occur in almost all parts of the body, including the nervous system, gastrointestinal system, endocrine system, skin, skeletal system, and vascular tissue. Autoimmune diseases are known to affect approximately 5-8% of the world's population, but the reported prevalence of autoimmune diseases is lower than the actual level due to limitations in our understanding of these diseases and in the methods used to diagnose them.

[0006] The etiology of autoimmune diseases has been extensively studied in terms of genetic, environmental, and immune factors, but a definitive identification remains elusive. Recent studies have revealed that many autoimmune diseases are caused by IgG type autoantibodies. In fact, research on the diseases and treatments of autoimmune diseases has broadly established the relationship between the presence or absence of disease-specific autoantibodies and their therapeutic effects. Therefore, the presence and pathological role of disease-specific autoantibodies in a large number of autoimmune diseases have been identified, and rapid therapeutic effects can be achieved when the target autoantibodies are removed from the blood.

[0007] Autoimmune diseases and alloimmune diseases are mediated by pathogenic antibodies, and common examples include immune neutropenia, Guillain-Barre syndrome, epilepsy, autoimmune encephalitis, Isaac syndrome, nevus syndrome, pemphigus vulgaris, pemphigus foliaceus, bullous pemphigoid, acquired epidermolysis bullosa, pemphigoid of pregnancy, mucosal pemphigoid, antiphospholipid syndrome, autoimmune anemia, autoimmune Graves' disease, Goodpasture syndrome, myasthenia gravis, multiple sclerosis, rheumatoid arthritis, lupus, idiopathic thrombocytopenic purpura (ITP), lupus nephritis or membranous nephropathy, or others.

[0008] Antibodies with novel mechanisms of action for treating autoimmune diseases by clearing pathogenic autoantibodies are expected to have therapeutic effects against pathogenic IgG-mediated autoimmune diseases (such as pemphigus, neuromyelitis optica, and myasthenia gravis) and immune complex-mediated glomerular diseases (such as lupus nephritis or membranous nephropathy).

[0009] Intravenous administration of large doses of IgG (IVIG) is widely used to treat autoimmune diseases (Arnson Auto Immunity 42:553, 2009). The effects of IVIG are explained by multiple mechanisms, including increased clearance of pathogenic antibodies through competition with endogenous IgG for Fc receptors. Intravenous administration of large doses of human immunoglobulin (IVIG) has been shown to increase platelet counts in children with immune ITP, and IVIG has also been shown to be beneficial as a therapy for several other autoimmune diseases. Numerous studies have investigated the mechanisms by which IVIG works in treating autoimmune diseases. For ITP, early studies concluded that the effect of IVIG was primarily due to the blockade of Fc receptors on platelets responsible for opsonizing antibodies. Subsequent studies showed that Fc-depleted IVIG formulations caused elevated platelet counts in some ITP patients, and more recently, the effect of IVIG has been reported to be attributed to stimulation of FcγRIIb expression on macrophages, leading to inhibition of platelet phagocytosis.

[0010] Using inhibitors that competitively inhibit the binding of IgG to FcRn is a promising treatment for autoimmune diseases. However, due to the high affinity of endogenous IgG for FcRn and the high concentration of endogenous IgG in the blood, competitive inhibition of FcRn may require extremely high doses and therefore has the same limitations as existing IVIG treatments. Summary of the Invention

[0011] The purpose of this invention is to overcome at least one deficiency of the prior art and to provide a VHH antibody against human FcRn and its application.

[0012] The technical solution adopted in this invention is:

[0013] The first aspect of the present invention provides:

[0014] A VHH antibody against human FcRn, comprising a framework region (FR) and a complementarity-determining region (CDR), wherein the amino acid sequences of the complementarity-determining regions CDR1 to CDR3 of the VHH antibody are selected from any of the following combinations:

[0015] Combination 1, the amino acid sequences of CDR1 to CDR3 are shown in SEQ ID NO.1 to SEQ ID NO.3, respectively;

[0016] Combination 2, the amino acid sequences of CDR1 to CDR3 are shown in SEQ ID NO.4 to SEQ ID NO.6, respectively;

[0017] Combination 3, the amino acid sequences of CDR1 to CDR3 are shown in SEQ ID NO.7 to SEQ ID NO.9, respectively.

[0018] In some examples of VHH antibodies, the FR of the VHH antibody is selected from any combination of the following:

[0019] Combination 1, the amino acid sequences of FR1 to FR4 are shown in SEQ ID NO.10 to SEQ ID NO.13, respectively;

[0020] Combination 2, the amino acid sequences of FR1 to FR4 are shown in SEQ ID NO.14 to SEQ ID NO.17, respectively;

[0021] Combination 3, the amino acid sequences of FR1 to FR4 are shown in SEQ ID NO.18 to SEQ ID NO.21, respectively.

[0022] In some examples of VHH antibodies, the VHH antibody is selected from one of the amino acid sequences shown below:

[0023] VHH-1: The amino acid sequences of its CDR1 to CDR3 are shown in SEQ ID NO.1 to SEQ ID NO.3, respectively, and the amino acid sequences of its FR1 to FR4 are shown in SEQ ID NO.10 to SEQ ID NO.13, respectively;

[0024] VHH-2: The amino acid sequences of its CDR1 to CDR3 are shown in SEQ ID NO.4 to SEQ ID NO.6, and the amino acid sequences of its FR1 to FR4 are shown in SEQ ID NO.14 to SEQ ID NO.17, respectively;

[0025] VHH-3: The amino acid sequences of its CDR1 to CDR3 are shown in SEQ ID NO.7 to SEQ ID NO.9, and the amino acid sequences of its FR1 to FR4 are shown in SEQ ID NO.18 to SEQ ID NO.21, respectively.

[0026] In some instances, VHH antibodies are chimeric antibodies, humanized antibodies, nanobodies fused with Fc fragments, or bivalent or multivalent nanobodies.

[0027] In some instances of VHH antibodies, the Fc fragment is selected from the Fc segment of human IgG1, IgG2, IgG3 or IgG4 or its variants or modifications.

[0028] In some examples of VHH antibodies, the amino acid sequence of the Fc fragment is: EPKSSDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMITRTPEVTCVVVAVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTPLHQDWLNGKEYKCKVSNKALPAGIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVGSCSVMHEALHAHYTQKSLSLSPGK.

[0029] A second aspect of the present invention provides:

[0030] A nucleic acid molecule encoding the VHH antibody described in the first aspect of this invention.

[0031] A third aspect of the present invention provides:

[0032] An expression vector comprising the nucleic acid molecule described in the second aspect of the present invention.

[0033] A fourth aspect of the present invention provides:

[0034] The application of the VHH antibody according to the first aspect of the present invention includes:

[0035] Preparation of diagnostic reagents for autoimmune diseases;

[0036] Preparation of FcRn adsorbent;

[0037] To prepare formulations for the treatment of autoimmune diseases;

[0038] Preparation of FcRn detection reagents;

[0039] Preparation of drug delivery carriers;

[0040] Fabrication of biosensors;

[0041] Reagents for preparing proteins for structural and functional studies.

[0042] VHH antibodies possess high specificity, enabling them to recognize and bind to specific antigens associated with autoimmune diseases. In autoimmune diseases, the body's immune system mistakenly attacks its own tissues and organs, producing antibodies against its own antigens. Furthermore, once VHH antibodies bind to the target antigen, they can generate detectable signals through various mechanisms.

[0043] In some application examples, the autoimmune disease is selected from one of the following: immune neutropenia, Guillain-Barre syndrome, epilepsy, autoimmune encephalitis, Isaac syndrome, nevus syndrome, pemphigus vulgaris, pemphigus foliaceus, bullous pemphigoid, acquired epidermolysis bullosa, pemphigoid of pregnancy, mucosal pemphigoid, antiphospholipid syndrome, autoimmune anemia, autoimmune Grave's disease, Goodpasture syndrome, myasthenia gravis, multiple sclerosis, rheumatoid arthritis, lupus, idiopathic thrombocytopenic purpura, lupus nephritis, and membranous nephropathy.

[0044] The beneficial effects of this invention are:

[0045] The VHH antibodies against human FcRn in some examples of this invention can specifically bind to human FcRn.

[0046] The VHH antibodies against human FcRn in some examples of this invention can replace traditional antibodies and be used in the treatment and diagnosis of autoimmune diseases.

[0047] The present invention provides VHH antibodies against human FcRn in some examples, which fuse Fc fragments to target and bind to FcRn receptors, thereby enhancing antibody targeting while effectively reducing the half-life of IgG in the blood.

[0048] The VHH antibodies against human FcRn in some examples of this invention, by fusing an Fc fragment, can increase their affinity for the FcRn receptor, effectively reduce the half-life of IgG in autoimmune diseases, and at the same time alleviate ADCC and CDC effects. Attached Figure Description

[0049] Figure 1 This is an electrophoresis image (45kD) of purified anti-human FcRn VHH-Fc antibody.

[0050] Figure 2 This is a schematic diagram showing the results of the VHH-Fc antibody binding activity assay against human FcRn. Detailed Implementation

[0051] The technical solution of the present invention will be further illustrated below with examples and experiments.

[0052] Example 1: Construction of VHH-Fc antibody specifically targeting human FcRn using alpaca natural library

[0053] Xinjiang Bactrian camels were immunized with FcRn protein expressed in CHO cells. After four immunizations, lymphocytes were extracted from 100 ml of peripheral blood of the camels, and total RNA was extracted. The extracted RNA was reverse transcribed into cDNA. Nested PCR was used to amplify the nucleic acid fragment encoding the variable region of the heavy chain antibody and the Fc fragment (the amino acid sequence of which is shown in SEQ ID NO. 22), constructing a VHH-Fc antibody phage display library targeting human FcRn. The library size was 1.33 × 10⁻⁶. 11 The insertion rate reached 100%.

[0054] The amino acid sequence of the Fc fragment is as follows:

[0055] EPKSSDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMITRTPEVTCVVVAVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTPLHQDWLNGKEYKCKVSNK ALPAGIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVGSCSVMHEALHAHYT QKSLSLSPGK (SEQ ID NO.: 22).

[0056] Example 2: Monoclonal bacterial screening of VHH-Fc antibodies targeting human FcRn

[0057] 100 nM biotinylated human FcRn was bound to magnetic beads at room temperature for 30 min. Unbound antigens were discarded. A blocked phage display library was then added to the magnetic beads and bound at room temperature for 1 h. Unbound phages were washed away with sodium acetate solution, and antigen-bound phages were eluted with Tris buffered saline solution at pH 7.4. The resulting phages were used to infect logarithmic-phase *E. coli* TG1 bacteria to generate and purify phages for the next round of screening. This screening process was repeated 2-3 times until positive clones were enriched.

[0058] Single colonies were selected from the enriched clones for phage ELISA testing. The ELISA plate was coated with 2 μg / mL FcRn protein and incubated overnight at 4°C, followed by three washes with PBST. The plate was then blocked with 2% skim milk at room temperature for 1 h, washed three times with PBST, and phage supernatant diluted with blocking buffer was added. The reaction was incubated at room temperature for 1 h, followed by six washes with PBST. Anti-M13 secondary antibody was added, and the reaction was incubated at room temperature for 1 h, followed by three washes with PBST. 100 μL of TMB substrate was added, and the reaction was terminated with 100 μL of 1M sulfuric acid. The absorbance was measured at 450 nm using a microplate reader. Clones with an OD450 value greater than 0.5 in the ELISA binding test were sequenced. Finally, three VHH-Fc antibodies with the best performance were selected and labeled NO.1–3, among which:

[0059] The VHH amino acid sequence of NO.1 is: QVQLVESGGGLVQPGGSLRLSCAASGFTESGSGFQYHAWFRQAPGKERERVALSWSGSRIRETISRDNSKNTVYLQMNSLRAEDTAVYYCAATADRMLGYPQGHEDDYGTLVTVSS (SEQ ID NO.23).

[0060] The VHH amino acid sequence of NO.2 is: QVQLVESGGGLVQPGGSLRLSCTGSGRGFTDFGIGWFRQAPGKERKFVAGISWSGHSTWYGDSVKGRFTISRDNAKNVVYLQMNDLQPEDTGVYYCGVIGLHLWGQGTEVTVSS (SEQ ID NO.24).

[0061] The VHH amino acid sequence of NO.3 is: AVQLVDSGGGLVQAGGSLRLSCEASGFTFDDYEIGWFRQAPGKEREGVSWIIPKYGDTYYADPVKGRFTISRGNAKSTVSLQMNSLKPEDTAVYYCAADVRTTEWGAPLRYWGQGTQVTVSS (SEQ ID NO.25).

[0062] Further analysis of the three VHHs determined their CDR and FR regions, and the analysis results are shown in Table 1.

[0063] Table 1. Structural analysis results of different VHH

[0064]

[0065] Example 3: In vitro expression and purification of VHH-Fc antibody targeting human FcRn

[0066] The gene sequence of the VHH-Fc antibody against FcRn (NO.1) was transferred into the PET28 plasmid via restriction enzyme sites and expressed in E. coli BL21. After expansion culture in LB medium containing 70 µg / mL kanamycin, the bacterial cells were collected, sonicated (5 s on, 10 s off, working time 20 min), centrifuged at 10,000 rpm for 10 min, and the supernatant was collected.

[0067] The target antibody was purified using protein A packing material and eluted with 0.1M acetic acid. SDS-PAGE electrophoresis analysis revealed that the expression level of VHH-Fc antibody was 38.4 mg / L.

[0068] Figure 1 This is an electrophoresis image of purified anti-human FcRn VHH-Fc antibody. The molecular weight of the VHH-Fc antibody is approximately 45 kD.

[0069] Example 4: Determination of VHH-Fc antibody affinity for anti-FcRn

[0070] The affinity of the antibody prepared in Example 3 was determined using the Octet@RED96 intermolecular interaction detection system. Ka (association rate constant) refers to the rate at which the antibody binds to the antigen to form an immune complex per unit time; a higher Ka value indicates rapid antibody-antigen binding. Kd (dissociation rate constant) refers to the rate at which the antibody dissociates from the antigen in the immune complex per unit time; a lower Kd value indicates that the antibody is less likely to dissociate after binding to the antigen. KD is the ratio of Ka to Kd, i.e., KD = Kd / Ka. The KD value reflects the affinity between the antibody and the antigen; the smaller the KD value, the higher the affinity between the antibody and the antigen. Human FcRn protein was diluted to 10 μg / mL, and the antibody obtained in Example 3 was diluted to 50 μg / mL. The dilution buffer used was PBS + 0.1% Tween 20 + 0.1% BSA. The affinity test results are shown in Table 2.

[0071] Table 2. Determination of VHH-Fc antibody affinity for anti-FcRn

[0072]

[0073] Table 2 shows that all three VHH-Fc antibodies obtained by screening have good affinity for FcRn protein, with NO.1 having the highest affinity for FcRn.

[0074] Example 5: Detection of the binding activity of VHH-Fc antibody against FcRn protein.

[0075] FcRn protein was serially diluted (1000 ng / mL, 500 ng / mL, 250 ng / mL, 125 ng / mL, 62.5 ng / mL, 31.25 ng / mL, 15.63 ng / mL) and added to 100 μL / well of an ELISA plate. The plate was incubated overnight at 4°C. After washing three times with PBST, 300 μL of 5% BSA was added, and the plate was blocked at 37°C for 2 h. After washing three times with PBST, 100 μL of diluted VHH-Fc antibody was added, and the plate was incubated at 37°C for 1 h. After washing six times with PBST, 100 μL of HRP-labeled M13 secondary antibody was added, and the plate was incubated at 37°C for 1 h. After washing six times with PBST, 100 μL of TMB substrate solution was added, and the plate was developed for 10 min. The absorbance was read at 450 nm. The results are shown below. Figure 2 As shown. From Figure 2 As can be seen, both VHH-Fc antibody and FcRn protein have binding activity, with NO1 exhibiting the highest binding activity.

[0076] The above is a further detailed description of the present invention and should not be considered as a limitation on the specific implementation of the present invention. For those skilled in the art, simple deductions or substitutions without departing from the concept of the present invention are all within the protection scope of the present invention.

Claims

1. A VHH antibody against human FcRn, comprising a framework region FR and a complementarity determining region CDR, characterized in that, The amino acid sequences of the CDR1~CDR3 of the VHH antibody are selected from any one of the following combinations: Combination 1, the amino acid sequences of the CDR1~CDR3 are respectively shown in SEQ ID NO.1~SEQ ID NO.3; Combination 2, the amino acid sequences of the CDR1~CDR3 are respectively shown in SEQ ID NO.4~SEQ ID NO.6; Combination 3, the amino acid sequences of the CDR1~CDR3 are respectively shown in SEQ ID NO.7~SEQ ID NO.

9.

2. The VHH antibody of claim 1, wherein, The FR of the VHH antibody is selected from any one of the following combinations: Combination 1, the amino acid sequences of the FR1~FR4 are respectively shown in SEQ ID NO.10~SEQ ID NO.13; Combination 2, the amino acid sequences of the FR1~FR4 are respectively shown in SEQ ID NO.14~SEQ ID NO.17; Combination 3, the amino acid sequences of the FR1~FR4 are respectively shown in SEQ ID NO.18~SEQ ID NO.

21.

3. The VHH antibody of claim 1, wherein, The VHH antibody is selected from one of the following amino acid sequences: VHH-1: the amino acid sequences of the CDR1~CDR3 are respectively shown in SEQ ID NO.1~SEQ ID NO.3, and the amino acid sequences of the FR1~FR4 are respectively shown in SEQ ID NO.10~SEQ ID NO.13; VHH-2: the amino acid sequences of the CDR1~CDR3 are respectively shown in SEQ ID NO.4~SEQ ID NO.6, and the amino acid sequences of the FR1~FR4 are respectively shown in SEQ ID NO.14~SEQ ID NO.17; VHH-3: the amino acid sequences of the CDR1~CDR3 are respectively shown in SEQ ID NO.7~SEQ ID NO.9, and the amino acid sequences of the FR1~FR4 are respectively shown in SEQ ID NO.18~SEQ ID NO.

21.

4. The VHH antibody according to any one of claims 1 to 3, characterized in that, It is a chimeric antibody, a humanized antibody, a nanobody fused with an Fc fragment, a bivalent or multivalent nanobody.

5. The VHH antibody of claim 4, wherein, The Fc fragment is selected from the Fc fragment of human IgG1, IgG2, IgG3 or IgG4 or a variant or modification thereof.

6. The VHH antibody of claim 4, wherein, The amino acid sequence of the Fc fragment is: EPKSSDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMITRTPEVTCVVVAVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTPLHQDWLNGKEYKCKVSNKALPAGIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVGSCSVMHEALHAHYTQKSLSLSPGK.

7. A nucleic acid molecule, characterized in that, A VHH antibody according to any one of claims 1 to 6.

8. An expression vector, characterized by, A nucleic acid molecule according to claim 7.

9. Use of a VHH antibody according to any one of claims 1 to 6, characterized in that, The use comprises: The preparation of a diagnostic reagent for FcRn-related autoimmune diseases, said autoimmune diseases being one selected from the group consisting of immune neutropenia, Guillain-Barre syndrome, epilepsy, autoimmune encephalitis, Isaac syndrome, nevus syndrome, pemphigus vulgaris, pemphigus foliaceus, bullous pemphigoid, acquired epidermolysis bullosa, pemphigoid gestationis, mucous membrane pemphigoid, anti-phospholipid syndrome, autoimmune anemia, autoimmune Grave's disease, Goodpasture's syndrome, myasthenia gravis, multiple sclerosis, rheumatoid arthritis, lupus, idiopathic thrombocytopenic purpura and membranous nephropathy.

10. Use according to claim 9, characterized in that, The lupus is lupus nephritis.

11. An FcRn adsorber, characterized in that A VHH antibody according to any one of claims 1 to 6.

12. An FcRn detection reagent, characterized in that, A VHH antibody according to any one of claims 1 to 6.

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