JP4942034B2 - Autoantibody adsorbent and extracorporeal circulation module - Google Patents

Description

  The present invention relates to an adsorbent for autoantibodies present in the blood of patients with pemphigus and an extracorporeal circulation module.

  Pemphigus is a serious disease that often causes blisters on the surface of the skin and mucous membranes, resulting in an intractable erosion and sometimes death. Epidemiologically, it is more common in women than men, and it occurs frequently in the 30s-60s with the peak in the 50s. Symptoms often begin in the visible mucosa, especially in the oral cavity, and blisters and eros eventually become generalized and exhibit generalized burns. The blisters are flaccid and easy to break, quickly erode, and further progress and spread the epidermis. Moreover, it is painful and afflicts patients. In particular, oral rash prevents eating and causes hypoproteinemia along with serum loss from a wide range of erosions on the skin. In the period of exacerbation, when the apparently normal skin surface is displaced with pressure applied by the fingertips, epidermis peeling occurs (Nicholsky phenomenon). Treatment is difficult, and it is designated as a specific disease in the country as a so-called intractable disease. If treatment is inadequate, death can occur due to atrophy and dysfunction of internal organs, as well as defense against infection.

  Pemphigus can be divided into two types, pemphigus vulgaris and deciduous pemphigus, according to clinical and histological characteristics. In all pemphigus, the lesion is intraepidermal blistering due to impaired cell-cell contact of keratinocytes (hereinafter referred to as “spin thawing”), but in pemphigus vulgaris, spinal lysis immediately above the basal layer. In deciduous pemphigus, blisters occur below the upper stratum corneum.

  In both pemphigus vulgaris and deciduous pemphigus, when the lesioned skin is examined by the fluorescent antibody method, IgG deposits are seen in epithelial cells, indicating a characteristic intercellular staining pattern. Furthermore, Non-Patent Documents 1 and 2 describe that IgG binding to the epithelial cell membrane surface was detected in patient blood. Non-patent document 3 shows that when IgG purified from a patient with pemphigus is injected into a newborn mouse, blisters having the same histological characteristics as those found in the patient are formed in the mouse skin. ing. Non-Patent Documents 4 and 5 report that the loss of cell adhesion occurs when IgG purified from a patient with pemphigus is added to the skin culture medium in which organ culture is performed. That is, patients with pemphigus produce IgG against self-epithelial tissue, and the IgG is thought to be responsible for the pathogenesis of loss of epithelial cell-cell adhesion in blister formation, which is the main pathology of pemphigus.

  In Non-Patent Documents 6 to 11, immunochemical analysis of antigens targeted by pemphigus vulgaris and deciduous pemphigus antibodies revealed that they are 130 kD and 160 kD glycoproteins, respectively. . Furthermore, in Non-Patent Documents 12 and 13, it is clear that cDNAs are used to clone these antigen molecules into a subfamily of desmoglein (hereinafter referred to as “Dsg”) belonging to the cadherin supergene family, which is an intercellular adhesion molecule. It was done. In Non-Patent Document 14, the target antigens for pemphigus vulgaris and deciduous pemphigus are now called desmoglein 3 (hereinafter referred to as “Dsg3”) and desmoglein 1 (hereinafter referred to as “Dsg1”), respectively. It is described that.

  According to the description in Non-Patent Document 15, in patients with pemphigus, autoantibodies against Dsg1 or Dsg3, which is one of the cell adhesion factors cadherin in the epithelium, are produced, and the antibodies react with Dsg1 and Dsg3. It is thought that the function of Dsg as an adhesion factor is inhibited, and plasmin, complement and the like are secondarily activated to cause epidermis peeling.

  Currently, systemic administration of corticosteroids called steroids is used for treatment for patients with pemphigus, but plasma exchange therapy (including double filtration plasma exchange) is used in combination because of strong side effects. In addition, immunosuppressants and high-dose gamma globulin intravenous therapy are being studied. Steroids and immunosuppressants are thought to suppress autoimmune effects, and long-term administration is known to cause serious side effects such as worsening of infections and osteonecrosis of the head. Plasma exchange therapy and high-dose gamma globulin intravenous therapy are thought to remove or neutralize the etiological antibody, but use blood plasma components from donated blood, which may infect viruses and unknown pathogens. Therefore, the current treatment method for pemphigus is not sufficient for all patients, and a new treatment method is desired. As one of them, therapeutic devices that selectively adsorb autoantibodies against Dsg3 or Dsg1 are being studied.

  In Patent Document 1, a target protein of pemphigus vulgaris is a similar protein of cadherin, which is a protein responsible for cell adhesion, and a fusion protein of protein Dsg3 and IgG, which is also considered to be involved in cell adhesion, is vulgaris. It is described that it is used for the treatment of pemphigus, and a therapeutic device for pemphigus vulgaris characterized by having an adsorbent material in which the fusion protein is immobilized on a carrier.

  In Patent Document 2, a target protein of deciduous pemphigus is a similar protein of cadherin, which is a protein responsible for cell adhesion, and a fusion protein of protein Dsg1 and IgG, which is also considered to be involved in cell adhesion, is disclosed in Patent Document 2. It is described that it is used for the treatment of pemphigus vulgaris, and a therapeutic device for deciduous pemphigus characterized by having an adsorbent in which the fusion protein is immobilized on a carrier has been devised.

However, in both Patent Documents 1 and 2, since the ligand immobilized on the carrier is a fusion protein, the antigenicity of the ligand becomes a problem, and the storage stability and sterilization stability of the ligand are poor, In addition, there is a risk of hydrolysis when it comes into contact with blood or plasma during extracorporeal circulation. Furthermore, the production of fusion proteins is a bioprocess, which requires a lot of labor for production, high production costs, high risk of endotoxin contamination during production, and endotoxin removal to ensure sufficient safety. The purification process is very laborious and costly, and has the disadvantage that the labor, equipment, time, cost, etc. for producing the ligand are enormous.
EHBeutner et al., Proc Soc Exp Biol Med, 1964, 117, pp. 505-510 Stanley et al., Journal of Clinical Investigation, 1989, 83, 1443-1448 GJAnhalt et al., New England Journal of Medicine, 1982, 306, 1189-1196 Hashimoto et al., Journal of Experimental Medicine, 1983, 157, 259-272 JRSchiltz et al., Journal of Investigative Dermatology, 1976, 67, 254-260 JRStanley et al., Journal of Clinical Investigation, 1982, 70, 281-288 Stanley et al., Journal of Clinical Investigation, 1984, 74, pp. 313-320 L. Koulu et al., Journal of Experimental Medicine, 1984, 160, 1509-1518 RWEyre et al., Journal of Clinical Investigation, 1988, 81, 807-812, Hashimoto et al., Journal of Investigative Dermatology, 1990, 94, 327-331 NJ Korman et al., New England Journal of Medicine, 1989, No. 321, 631-635 European Journal of Cell Biology, 53, 1-12, 1990, PJKoch et al. Amagaya et al., Cell, 1991, 67, 869-877 RSBuxton et al., Journal of Cell Biology, 1993, 121, 481-483 Masayuki Amaya, 1992, Modern Medicine, 47, 159-161 JP-A-8-188540 JP-A-9-77800

  An object of the present invention is to provide an adsorbent and a therapeutic adsorber excellent in safety and storage stability, which adsorb autoantibodies of pemphigus patients and further autoantibodies against Dsg.

  As a result of intensive studies to solve the above-mentioned problems, the present inventors have made it possible for an adsorbent in which a ligand comprising a thienyl group-containing compound is immobilized on a water-insoluble carrier to selectively detect autoantibodies in patients with pemphigus. And it adsorb | sucked at high rate and it discovered that it was excellent in safety | security and storage stability, and came to complete this invention. That is, the present invention relates to the following.

(1) A pemphigus autoantibody adsorbent, wherein a ligand comprising a compound containing a thienyl group is immobilized on a water-insoluble carrier.
(2) An autoantibody adsorbent for desmoglein, wherein a ligand comprising a compound containing a thienyl group is immobilized on a water-insoluble carrier.
(3) The autoantibody adsorbent according to (1) or (2), wherein the ligand has 4 to 8 carbon atoms.
(4) The autoantibody adsorbent according to any one of (1) to (3), wherein the ligand is 2-thiophenethylamine.
(5) The autoantibody adsorbent according to any one of (1) to (4), wherein the amount of the ligand immobilized is 10 μmol to 200 μmol per ml of a water-insoluble carrier.
(6) The autoantibody adsorbent according to any one of (1) to (5), wherein the water-insoluble carrier is a particulate porous body and has an exclusion limit molecular weight of 150,000 to 10,000,000. .
(7) A container having an inlet port through which blood or plasma flows and an outlet port through which blood or plasma flows out is filled with the autoantibody adsorbent according to any one of (1) to (6). Extracorporeal circulation module.

  The autoantibody adsorbent according to the present invention can adsorb pemphigus autoantibodies and autoantibodies against Dsg. In particular, the anti-Dsg antibody (anti-Dsg1 antibody, anti-Dsg3 antibody) is selectively and highly adsorbed, and the adsorbent is excellent in safety and storage stability. Further, by using an extracorporeal circulation module enclosing the adsorbent, pemphigus autoantibodies including anti-Dsg antibodies (anti-Dsg1 antibody, anti-Dsg3 antibody) can be safely removed from the blood of a pemphigus patient by extracorporeal circulation.

The present invention will be described in detail below.
The ligand referred to in the present invention needs to be a ligand composed of a compound containing a thienyl group. The number of thienyl groups contained in the ligand is not particularly limited, but is preferably 1 to 5 in view of the chemical stability and blood compatibility of the ligand.

  The number of carbon atoms in the ligand referred to in the present invention is preferably 4 or more and 8 or less. If the number of carbon atoms is 4 or less, the adsorptivity of anti-Dsg antibodies (anti-Dsg1 antibody and anti-Dsg3 antibody) will be significantly reduced. If the number of carbon atoms of the ligand exceeds 8, the hydrophobicity of the ligand increases and the anti-Dsg antibody (anti-Dsg1 antibody, anti-Dsg3 antibody) adsorbability increases, but other proteins in plasma also adsorb. Specific adsorption occurs, resulting in poor blood compatibility. Further, the solubility and storage stability at the time of ligand fixation are also deteriorated, which is not preferable.

  The ligand composed of a compound containing a thienyl group is preferably an amine compound having one or more primary amines effective for immobilization on a carrier and adsorption of an anti-Dsg antibody. Specific examples include thienylglycine, thienylalanine, and thienylserine, which are amino acids containing a thienyl group. The amino acids and amino acid derivatives described in this specification are L-forms unless otherwise specified. Furthermore, 2-thiophenethylamine, which is a compound containing a thienyl group that does not contain a carboxylic acid, is more excellent as an anti-desmoglein antibody adsorbing ability than an amino acid containing a thienyl group, and therefore can be suitably used as a ligand.

  The water-insoluble carrier referred to in the present invention refers to a carrier that is hardly soluble in water to the extent that the adsorbent does not dissolve in blood when it comes into contact with blood.

  As a carrier used for immobilizing a low molecular ligand, an amino group, a carboxyl group, a hydroxyl group, etc. that have a hydrophilic surface and can be used to form a covalent bond with the low molecular ligand. Those having a reactive functional group are preferred. The water-insoluble carrier is desirably a porous material having a wide effective surface area that can be adsorbed.

  The carrier can be in any shape such as particulate, fiber, sheet, hollow fiber, etc. However, in consideration of the amount of ligand retained and the handling property as an adsorbent, the carrier is preferably particulate.

  A spherical or particulate carrier having an average particle diameter of 25 μm to 2500 μm can be used, but considering its specific surface area (adsorption ability as an adsorbent) and the fluidity of body fluids, those having a particle diameter of 50 μm to 1500 μm are preferable.

  As the carrier that can be used, organic or inorganic porous materials such as cellulose gel, dextran gel, agarose gel, polyacrylamide gel, porous glass, vinyl polymer gel, etc. can be used, and they are used for ordinary affinity chromatography. Any material for the carrier can be used.

  Examples of these carriers include cellulose such as Asahi Kasei Microcarrier (manufactured by Asahi Kasei Co., Ltd.), CM-Cellulofine (registered trademark) CH (exclusion limit protein molecular weight: about 3 × 10 6, sold by Seikagaku Corporation). -Based carriers, polyvinyl alcohol-based carriers such as a total porous activated gel described in JP-B-1-44725, CM-Toyopearl (registered trademark) 650C (exclusion limit protein molecular weight: 5 × 106, manufactured by Tosoh Corporation), etc. , CM-Trisacryl M (CM-Trisacryl M) [exclusion limit protein molecular weight: 1 × 10 7, Pharmacia-LKB, Sweden] polyacrylamide carrier, Sepharose CL-4B (Sepharose CL-4B) ) [Exclusion limit protein molecular weight: 2 × 107, -Organic carrier such as agarose carrier such as Pharmacia-LKB (Pharmacia-LKB), and CPG-10-1000 [exclusion limit protein molecular weight: 1 × 10 8, average pore size: 100 nm, US electro-nucleo Inorganic supports such as porous glass such as those manufactured by Electro-nucleonics.

  The porous polymer particles used in the present invention can immobilize a ligand, and the exclusion limit molecular weight (protein) is 15 because the molecular weight of the target adsorbent of the present invention is about 150,000 (IgG). 10,000 to 10,000,000 is preferable. The most preferred exclusion limit molecular weight for the purposes of the present invention is between 1 and 5 million.

  The polymer composition may be a known polymer that can take a porous structure, such as a polyamide-based, polyester-based, polyurethane-based, or vinyl-based polymer. Particularly, a vinyl compound-based porous material that has been hydrophilized with a hydrophilic monomer. Sex polymers give favorable results.

  The method for immobilizing the ligand on the water-insoluble carrier is not limited, but a covalent bond is preferred. For example, when the carrier has a carboxyl group, it is converted to a succinimideoxycarbonyl group by reacting with N-hydroxysuccinimide, and this is reacted with a ligand at the amino group (active ester method). Can be mentioned. When the carrier has an amino group or a carboxyl group, a method of condensing the carboxyl group or amino group of the ligand in the presence of a condensation reagent such as dicyclohexylcarbodiimide (condensation method), Examples include a method of bonding using a compound having two or more functional groups. In addition, when the carrier has a hydroxyl group, a cyanogen halide such as cyanogen bromide is allowed to act on the carrier, and a method of reacting with the amino group portion of the ligand or an epoxide such as epichlorohydrin is allowed to act on the carrier, Examples thereof include a method of reacting with the amino group part or hydroxyl part of the ligand.

  Furthermore, if necessary, a molecule (spacer) having an arbitrary length can be introduced between the water-insoluble carrier and the ligand. Examples of the spacer molecule include a polymethylene chain and a polyethylene glycol chain. For example, the hydroxyl group of agarose and the isocyanate group on one side of hexamethylene diisocyanate can be reacted and bonded, and the remaining isocyanate group and the amino group, hydroxyl group, carboxyl group, etc. of the ligand can be reacted and bonded.

  The amount of ligand to be bound to the carrier in the present invention, that is, the amount of ligand retained is in the range of 10 μmol to 200 μmol, more preferably in the range of 10 μmol to 100 μmol, per ml of the carrier. When the retention amount is less than 10 μmol, the adsorption ability of the anti-Dsg antibody is lowered, and when it exceeds 200 μmol, nonspecific adsorption of plasma useful components occurs, which is not preferable.

  The pemphigus autoantibody referred to in the present invention means an antibody against a self-antigen that is a pathogen of pemphigus. In particular, adsorbing and removing autoantibodies against Dsg3 and Dsg1, which are target antigens of pemphigus vulgaris and deciduous pemphigus, that is, anti-Dsg antibodies (anti-Dsg1 antibody and anti-Dsg3 antibody) is an effective treatment method. Become.

  As a method of measuring the amount of anti-Dsg antibody (anti-Dsg1 antibody and anti-Dsg3 antibody) adsorbed on the anti-Dsg antibody adsorbent, an anti-Dsg antibody solution is added to the anti-Dsg antibody adsorbent, and anti-Dsg antibody (anti-Dsg1 antibody and anti-Dsg1 antibody Dsg3 antibody) is adsorbed, and the reduction rate of the anti-Dsg antibody (anti-Dsg1 antibody and anti-Dsg3 antibody) in the anti-Dsg antibody solution is measured. For example, the carrier on which the ligand is immobilized is immersed in an anti-Dsg antibody (anti-Dsg1 antibody and anti-Dsg3 antibody) solution for a certain period of time, and then the reduction rate of anti-Dsg antibody (anti-Dsg1 antibody and anti-Dsg3 antibody) is determined by ELISA. It can be determined quantitatively by the method.

  The autoantibody adsorbent of the present invention can be used while being filled and held in a container having a body fluid outlet.

  In FIG. 1, reference numeral 1 denotes an example of an extracorporeal circulation module using the autoantibody adsorbent of the present invention. Body fluid is introduced into one end opening of a cylinder 2 through a packing 4 with a filter 3 inside. A cap 6 having a mouth 5 is screw-fitted, and a cap 8 having a body fluid outlet 7 is screw-fitted through a packing 4 ′ with a filter 3 ′ on the inside of the other end opening of the cylinder 2. The adsorbent layer 9 is formed by filling and holding the adsorbent in the gap between the filters 3 and 3 '.

  The adsorbent layer 9 may be filled with the autoantibody adsorbent of the present invention alone, or may be mixed or laminated with other adsorbents. As other adsorbents, for example, adsorbents of other malignant substances (antigens) such as DNA, activated carbon having a wide range of adsorption ability, and the like can be used. As a result, a wide range of clinical effects due to the synergistic effect of the adsorbent can be expected. The volume of the adsorbent layer 9 is appropriately about 50 ml to 400 ml when used for extracorporeal circulation.

  When the extracorporeal circulation module of the present invention is used for extracorporeal circulation, there are the following two methods. For one thing, after separating the blood taken from the body into a plasma component and a blood cell component using a centrifuge or a membrane plasma separator, the plasma component is passed through the extracorporeal circulation module and purified. This is a method of returning the blood cell component together with the blood cell component, and the other one is a method of purifying the blood taken out from the body through the extracorporeal circulation module directly.

  As for the passing speed of blood or plasma, since the adsorption capacity of the adsorbent of the present invention is very high, the particle size of the adsorbent can be coarsened, and the degree of filling can be lowered. Regardless of this, a high passage speed can be provided, so that a large amount of body fluid can be treated.

  As a body fluid passing method, it may be continuously passed or used intermittently depending on clinical necessity or according to the equipment status of the facility.

EXAMPLES Hereinafter, although an Example demonstrates this invention further in detail, this invention is not limited to these.
[Examples 1 to 4]

1. Preparation method of adsorbent Spherical porous body made of polyvinyl acetate (manufactured by Asahi Glass Co., Ltd., average particle size of 100 μm, exclusion limit molecular weight of about 1 million or more, and the amount of pullulan having a molecular weight of 40,000 that can be filled in 1 ml of resin is 0.20 ml. 100 ml of / ml or more) is charged into 1 liter of dimethyl sulfoxide (Wako Pure Chemical Industries, Ltd.), 120 g of sodium hydroxide (Wako Pure Chemical Industries, Ltd.) 120 g, epichlorohydrin (Wako Pure Chemical Industries, Ltd.) 780 ml, hydrogenated Epoxy groups were introduced by reacting 750 mg of sodium boron (manufactured by Wako Pure Chemical Industries, Ltd.) at 30 ° C. for 5 hours. After the reaction, it was washed with methanol (manufactured by Wako Pure Chemical Industries, Ltd.) and then washed with pure water to obtain an activated porous material. The amount of epoxy group introduced into the obtained porous material is 110 μeq / mlgel or more, and titration method (1.3 mmol / l sodium thiosulfate aqueous solution (manufactured by Wako Pure Chemical Industries, Ltd.) 4 ml and activated carrier 2 ml) 2 drops of a 1% phenolphthalein ethanol solution (manufactured by Wako Pure Chemical Industries, Ltd.) and 0.1N hydrochloric acid are added at 70 ° C. until red coloration is not confirmed. The amount of the introduced epoxy group was determined by the formula of “hydrochloric acid titration / resin amount × 100” and confirmed that it was 110 μeq / ml gel or more.

2. Immobilization reaction Next, a carbonate buffer solution of pH 9.3 (Wako Pure Chemical Industries, Ltd., sodium carbonate / sodium hydrogen carbonate) was used as a solvent, and for Examples 1 to 4, a fixed amount of 50 μeq / ml gel was obtained. Ligand was dissolved. The prepared ligand solution and carrier were reacted at 50 ° C. for 16 hours to covalently bond the amino group and the porous epoxy group to obtain an adsorbent. As a ligand, Example 1: Thienylglycine (L-α- (3-THIENYL) GLYCINE), Example 2: Thienylserine (β- (2-THIENYL-DL-SERINE)), Example 3: Thienylalanine (β -(2-THIENYL) -D-ALANINE)) (Examples 1 to 3, glue gund is made by SIGMA), Example 4: 2-thiophenethylamine (2-THIOPHENEETHYLAMINE) (made by Wako Pure Chemical Industries, Ltd.) Was used. The amount of immobilization was calculated as the amount of immobilization per 1 ml gel (eq / ml gel) from the difference between before and after the reaction by measuring the absorbance spectrum of the ligand solution at a wavelength of 200 nm to 280 nm and using the wavelength showing the highest absorbance.

3. Adsorption reaction 0.5 ml of adsorbent was added per well to a microplate (Falcon, No. 3504), and 1.0 ml of pemphigus patient plasma was added thereto and reacted at room temperature for 60 minutes with shaking.

4). The adsorbent was removed from the plasma after the analysis reaction to prepare a sample. The concentration of pemphigus autoantibodies (anti-Dsg1 antibody and anti-Dsg3 antibody) was detected by ELISA, and the difference between the amount of anti-Dsg antibody in the original plasma and the amount of anti-Dsg antibody in the serum after reaction was calculated as the amount of adsorption. The adsorption performance was calculated by the equation “adsorption rate (%) = (1−plasma concentration after adsorption reaction / original plasma concentration) × 100”.

[Comparative Examples 1 to 12 and Reference Example]
As a comparative example, the immobilization reaction was carried out in the same manner as described in the Examples, except that a compound having 6 or less carbon atoms and not containing a thienyl group was used as a ligand. The immobilization reaction was carried out with a fixed amount of 50 μeq / ml gel. The ligand was dissolved in a solvent as obtained. In addition, as a reference example, the reaction was carried out in the same manner as described in the Examples using an activated carrier that does not immobilize the ligand.
As ligands, Comparative Example 1: Glycine, Comparative Example 2: Alanine, Comparative Example 3: Serine, Comparative Example 4: Cysteine, Comparative Example 5: Threonine, Comparative Example 6: Asparagine, Comparative Example 7: Aspartic Acid, Comparative Example 8: Methionine, Comparative Example 9: Proline, Comparative Example 10: Histidine, Comparative Example 11: Isoleucine, Comparative Example 12: Arginine (The ligands of Comparative Examples 1 to 12 were manufactured by SIGMA).

[result]
The results of Examples 1 to 4, Comparative Examples 1 to 12, and Reference Example (no ligand) are shown in Table 1. As a result, the adsorbents having ligands with thienyl groups of the examples all have higher adsorption rates of anti-Dsg1 antibody and anti-Dsg3 antibody than the comparative examples, and selectively adsorb them from the plasma of patients with pemphigus. You can see that

<Examples 5 to 8 and Reference Examples>
The same procedure as in Examples 1 to 4 was performed, except that 2-thiophenethylamine was used as the ligand and the reaction was carried out so that the amount of immobilized ligand was 0, 5, 10, 50, and 100 μeq / ml gel. The concentration of pemphigus autoantibodies (anti-Dsg1 antibody and anti-Dsg3 antibody) was detected by ELISA. The results are shown in Table 2. As a result, it can be seen that when the amount of immobilized ligand is 10 μeq / ml or more, the adsorption rate of anti-Dsg1 antibody and anti-Dsg3 antibody is high.

  Since the present invention selectively and highly adsorbs autoantibodies and anti-desmoglein antibodies (anti-Dsg1 antibody, anti-Dsg3 antibody) of patients with pemphigus, it is useful as a therapeutic instrument for extracorporeal circulation adsorption therapy.

An example of an extracorporeal circulation module using the autoantibody adsorbent of the present invention is shown.

Explanation of symbols

DESCRIPTION OF SYMBOLS 1 ... Extracorporeal circulation module 2 which uses an autoantibody adsorption material ... Cylindrical 3, 3 '... Filter 4, 4' ... Packing 5 ... Body fluid inlet 6 ... Cap 7 ... Body fluid outlet 8 ... Cap 9 ... Auto antibody adsorption material

Claims (7)

Thienyl seen including, autoantibodies adsorbent against desmoglein ligand consisting of aminated compound having a primary amine, one or more is characterized in that it is immobilized on a water-insoluble carrier. The autoantibody adsorbent according to claim 1 , wherein the ligand has 4 to 8 carbon atoms. The autoantibody adsorbent according to claim 1, wherein the compound is any one of thienylglycine, thienylserine, thienylalanine, and 2-thiophenethylamine. The autoantibody adsorbent according to claim 1 , wherein the compound is 2-thiophenethylamine.   The autoantibody adsorbent according to any one of claims 1 to 4, wherein the immobilized amount of the ligand is 10 µmol to 200 µmol per 1 ml of the water-insoluble carrier.   The autoantibody adsorbent according to any one of claims 1 to 5, wherein the water-insoluble carrier is a particulate porous body and has an exclusion limit molecular weight of 150,000 to 10,000,000. An extracorporeal circulation module, wherein the autoantibody adsorbent according to any one of claims 1 to 6 is filled in a container having an inlet port through which blood or plasma flows in and an outlet port through which blood or plasma flows out. .

Images