Abstract: Activated immunoglobulin which is useful as an eosinophilia-suppressing agent, immunomodulating agent, therapeutic agent for autoimmune diseases, anfiinflammatory agent and antiallergic agent is obtained by admixing immunoglobulin with a histamine component and then substantially or completely removing the histamine component. The histamine component may be removed or separated by dialysis, gel filtration, adsorption chromatography, ion exchange chromatography, or affinity chromatography. The method imparts pharmacological activity which is not inherently available in immunoglobulin of the natural type to immunoglobulin. The activated immunoglobulin of the present invention has an immunomodulating action which is clearly different from that of conventional immunosuppressive agents.

Abstract: Compositions for stabilizing polypeptides or antigens are described. These compositions are useful for stabilizing polypeptides or antigens stored in aqueous formulations. Such formulations can be used for various analytical or other methods.

Abstract: The level of CD8+ T cell cytotoxicity directed toward activated CD4+ T cells expressing a specific T cell receptor V&bgr; chain and a major histocompatibility complex class Ib molecule is assayed by contacting a sample containing CD8+ T cells with the activated CD4+ T cells for a determined period of time and determining the amount of activated CD4+ T cell death during the time period. The level of CD8+ T cell activity stimulated by the activated CD4+ T cells is assayed by measuring lymphokine release from stimulated CD8+ T cells or by determining the amount of cell surface molecules specifically expressed on stimulated CD8+ T cells. An agent capable of stimulating or inhibiting CD8+ T cells cytotoxicity toward the activated CD4+ T cells will suppress or inhibit the suppression of an immune response mediated by the activated CD4+ T cells, respectively.

Abstract: An autoimmune vaccine is provided for administration to human patients to alleviate the symptoms of autoimmune diseases such as rheumatoid arthritis. The vaccine comprises an aliquot of the patient's blood, containing, inter alia, leukocytes having upregulated expression of various cell surface markers and lymphocytes containing decreased amounts of certain stress proteins. It is produced by subjecting the blood aliquot extracorporeally to certain stressors, namely oxidizing agents, UV radiation and elevated temperature.

Abstract: In the present invention, pharmaceutical compositions containing a histamine-added gamma-globulin as an effective component are used as an immunomodulating agent, a suppressive agent for eosinophilia, and as an antiinflammatory agent. The immunomodulating action is unexpectedly different from the action of conventional immunosuppressive agents. Accordingly, the compositions are useful as a pharmaceutical agent for the therapy of diseases associated with an abnormal immune system such as chronic articular rheumatism, systemic lupus erythematosus, multiple sclerosis, etc. and various types of immunodeficiency syndromes. In addition, the pharmaceutical compositions exhibit suppressive action upon hypereosinophilicity. They may be used as a therapeutic agent for infectious diseases, parasitic diseases, respiratory diseases, autoimmune diseases and eosinophilia caused by malignant tumors. The compositions are excellent antiinflammatory agents.

Abstract: The invention relates to the treatment of individuals suffering from a disease associated with leukocyte recruitment to the gastrointestinal tract or other tissues as a result of binding of leukocytes to gut-associated endothelium expressing the molecule MAdCAM (such as inflammatory bowel disease), comprising administering to the individual an effective amount of an antibody which inhibits the binding of leukocytes to endothelial MAdCAM.

Abstract: A chimeric protein comprising a Pseudomonas aeruginosa exotoxin (PE) moiety linked to a myelin basic protein (MBP) moiety is disclosed. The MBP moiety is selected from the group comprising: (a) MBP; (b) amino acids 69-88 of guinea-pig myelin basic protein or an antigenic portion thereof; (c) amino acids 84-102 of human myelin basic protein or an antigenic portion thereof; (d) amino acids 143-168 of human myelin basic protein or an antigenic portion thereof; and (e) an amino acid sequence in which one or more amino acids have been deleted, added, substituted or mutated in the amino acid sequences of (a), (b), (c) or (d), the modified sequence of (e) retaining at least 75% homology with the amino acid sequences of (a), (b), (c) or (d), respectively. Each of the MBP moieties of (b), (c) and (d) are linked to the PE moiety by a pentapeptide linker repeated 1-3 times. The chimeric protein is useful in treating autoimmune diseases, and especially multiple sclerosis.

Abstract: Human antibodies, preferably recombinant human antibodies, that specifically bind to human tumor necrosis factor &agr; (hTNF&agr;) are disclosed. These antibodies have high affinity for hTNF&agr; (e.g., Kd=10−8 M or less), a slow off rate for hTNF&agr; dissociation (e.g., Koff=10−3 sec−1 or less) and neutralize hTNF&agr; activity in vitro and in vivo. An antibody of the invention can be a full-length antibody or an antigen-binding portion thereof. The antibodies, or antibody portions, of the invention are useful for detecting hTNF&agr; and for inhibiting hTNF&agr; activity, e.g., in a human subject suffering from a disorder in which hTNF&agr; activity is detrimental. Nucleic acids, vectors and host cells for expressing the recombinant human antibodies of the invention, and methods of synthesizing the recombinant human antibodies, are also encompassed by the invention.

Abstract: Provided are methods for treating inflammatory diseases in a patient comprising administering to the patient an effective amount of a conjugate consisting essentially of one or more antibody fragments covalently attached to one or more nonproteinaceous polymer molecules, wherein at least one antibody fragment comprises an antigen binding site that binds to human IL-8, and wherein the apparent size of the conjugate is at least about 500 kD.

Abstract: Pharmaceutical applications of a chemodenervating agent reduce pain by altering release of pain and inflammation-mediating autocoids, with a duration of action between 12-24 weeks. The limiting factor in dosing for this application is weakness and paralysis created by higher doses of the chemodenervating pharmaceutical. This weakness and paralysis is mediated by action of the neurotoxin component of the chemodenervating pharmaceutical. The invention described herein represents a novel mechanism and pharmaceutical formulation which eliminates the neurotoxin component of the chemodenervating pharmaceutical, while retaining the cytotoxin component which provides an essential bioeffect for the relief of pain and inflammation. The invention allows for improvement in administering the pharmaceutical agent for the reduction of pain and/or inflammation without causing muscular weakness and paralysis.

Abstract: Peptides that are capable of suppressing autoimmune arthritis are disclosed. The polypeptides described by the present invention which are capable of suppressing autoimmune arthritis in mammals include analogues of CII 245-270. The peptides do not provoke a material immunogenic response from T cells, and thus are useful therapeutic agents for suppressing autoimmune arthritis, rheumatoid arthritis, juvenile arthritis, psoriatic arthritis, spondylo arthritis, relapsing polychondritis and other connective tissue diseases. A method of surpressing autoimmune arthritis in mammals is also provided by the present invention.

Abstract: Methods are described for treating inflammatory bowel disease in animals, including humans. Specific avian polyclonal antibodies directed to TNF are shown to have a beneficial effect in animal models predictive of human therapy for the treatment of colitis.

Abstract: An agent comprising a mucosa-binding molecule linked to a specific microbial antigen is disclosed. Further, a method of inducing immnunological tolerance in an individual against a specific microbial antigen, including hapten, which causes an unwanted immune response in said individual, comprising administration by a mucosal route of an immunologically effective amount of an immunological tolerance-inducing agent of the invention to said individual, is described.

Abstract: The prevention and treatment of autoimmune disease in humans (as well as other animals) is described through the use of ligands directed to cytokines. Antibodies and receptors to the proinflammatory cytokines IL-2, TNF, IL-12 and IFN-gamma are employed (along with other ligands to such cytokines). Such ligands administered luminally are effective (as demonstrated in two experimental models of autoimmune disease) at delaying the onset of autoimune disease.

Abstract: Disclosed are methods and compositions useful for the treatment of autoimmune diseases. Methods for producing vaccines against autoreactive T-cells are disclosed. The vaccines so produced are capable of restoring a degree of immunologic self-tolerance sufficient to slow or halt the progression of autoimmune disorders. In a preferred embodiment of the invention, a vaccine is derived from attenuated autologous autoreactive T-cells that recognize a variety of myelin-derived proteins. Such vaccine compositions are useful for immunologic therapy for the treatment of multiple sclerosis (MS).

Abstract: The invention provides methods and compositions for inhibiting pathogenic binding of an pathogenic autoantibody to a myelin oligodendrocyte glycoprotein (MOG) autoantigen and screening for inhibitors of pathogenic binding of an autoantibody to a MOG autoantigen.

Abstract: The invention provides a method for preventing allergic disease in an individual susceptible to such disease, comprising administering an allergen to which the individual has not been sensitized previously. The allergen is administered in a dose and form effective to establish a stable population of allergen-specific T-helper-1-like memory lymphocytes capable of inhibiting activity or amplification of allergen-specific T-helper-2-like lymphocytes responsible for stimulating production of IgE antibodies specific for the allergen. Compositions for use in the method of the invention are also disclosed.

Abstract: An immunological tolerance-inducing agent comprising a mucosa-binding molecule linked to a specific tolerogen is disclosed. Further, a method of inducing immunological tolerance in an individual against a specific antigen, including hapten, which causes an unwanted immune response in said individual comprising administration by a mucosal route of an immunologically effective amount of an immunological tolerance-inducing agent of the invention to said individual, is described.

Abstract: Compositions are administered to block IgE binding to receptors and ultimately displace native IgE from mast cells and related cell types, to prevent the activation of these cells during an allergic response. The compositions consist of a pharmaceutically acceptable carrier for systemic or local administration and an amount of compound binding specifically to the Fc&egr;RI IgE binding sites, and more preferably, Fc&egr;RI and Fc&egr;RII IgE binding sites, to prevent activation and degranulation of mast cells in response to exposure to allergens. The compounds can consist of IgE molecules and fragments and modifications thereof, such as IgE fragments, humanized or single chain IgE antibodies or fragments thereof, IgE with a modified Fab, non-crosslinkable IgE, or peptidomimetics which bind to the same site on the receptor as the IgE, jointly referred to herein as “IgE fragments” unless otherwise stated.

Abstract: The present invention relates to a method for adjusting the affuinity of a polypeptide to a target molecule by a combination of steps, including: (1) the identification of aspartyl residues which are prone to isomerization; (2) the substitution of alternative residues and screening the resulting mutants for affinity against the target molecule. In a preferred embodiment, the method of subtituting residues is affinity maturation with phage display (AMPD). In a further preferred embodiment the polypeptide is an antibody and the target molecule is an antigen. In a further preferred embodiment, the antibody is anti-IgE and the target molecule is IgE. In another embodiment, the invention relates to an anti-IgE antibody having improved affinity to IgE.

Abstract: The invention relates to compounds, such as proteins, peptides and organic compounds, capable of blocking or inhibiting the binding interaction of Raf-1 or 14-3-3 proteins to the &bgr; chain of IL-2, and pharmaceutical compositions containing such compounds. In vitro assays for isolating, identifying and characterizing such compound capable of inhibiting interaction of Raf-1 or 14-3-3 proteins to IL-2&bgr; are also provided.

Abstract: The development of graft versus host disease in a mammalian patient undergoing cell transplantation therapy for treatment of a bone marrow mediated disease, is prevented or alleviated by subjecting at least the T-cells of the allogeneic cell transplantation composition, extracorporeally, to oxidative stress, in appropriate dosage amounts, such as bubbling a gaseous mixture of ozone and oxygen through a suspension of the T-cells. The process may also include irradiation of the cells with UV light, simultaneously with the application of the oxidative stress. The oxidative stress induces reduced inflammatory cytokine production and a reduced proliferative response in the T-cells.

Abstract: Methods for detecting the status of an insulin-dependent diabetes mellitus (IDDM)-associated autoimmune response in a mammal are provided. Specifically, the ratio of the frequency of T helper 1 cells to T helper 2 cells specific for a pancreatic &bgr;-cell associated antigen is indicative of the status of the autoimmune response. The methods may be employed prior to the onset of the clinical symptoms of the disease, thereby allowing identification of those at risk for developing clinical symptoms of IDDM, or subsequent to pancreatic tissue transplantation, for example, to measure the efficacy of treatment directed to enhancing the lifetime of the tissue transplant. Methods for prolonging the survival of tissue transplants are also provided. Specifically, a tissue-associated antigen is administered to the mammal which serves to shift the pathogenic Th1 response associated with pathological immunity toward a protective Th2 response.

Abstract: The invention concerns pharmaceutically useful peptide derivatives of the formula (I), P—R1—R2—R3—R4, in which P, R1, R2, R3, and R4 have the various meanings defined herein, and their pharmaceutically acceptable salts, and pharmaceutical compositions containing them. The novel peptide derivatives are of value in treating MHC class II dependent T-cell mediated autoimmune or inflammatory diseases, such as rheumatoid arthritis. The invention further concerns processes for the manufacture of the novel peptide derivatives and the use of the compounds in medical treatment.

Abstract: Common allergenic foods are made hypoallergenic by treatment with super critical fluid or critical liquid gas such as super critical carbon dioxide or liquid nitrogen. The treatment of foods with liquid nitrogen or super critical carbon dioxide also enhances the functionality of fat, so that the total fat in the food can be reduced while retaining the good taste of the food.

Abstract: The subject invention concerns novel materials and methods for the treatment and/or prevention of autoimmune disease. In a specific embodiment, elevated production of prostaglandin synthase-2 (PGS-2) is correlated with autoimmune dysfunction.

Abstract: An agent comprising a mucosa-binding molecule linked to a specific microbial antigen is disclosed. Further, a method of inducing immunological tolerance in an individual against a specific microbial antigen, including hapten, which causes an unwanted immune response in said individual, comprising administration by a mucosal route of an immunologically effective amount of an immunological tolerance-inducing agent of the invention to said individual, is described.

Abstract: A process for the detection of cpn10 in serum or other biological fluids including the steps of (i) raising antibody to cpn10; (ii) reacting said antibody with a sample of biological fluid suspected of containing cpn10; and (iii) detecting the presence of cpn10 in said sample by a signal amplification resulting from production of a cpn10-antibody complex. There is also provided a process for promotion of cell growth or immunosuppression including the step of administration of cpn10 to a mammalian subject. There is also provided recombinant cpn10.

Abstract: Compositions comprising anti-CD45RB antibodies are provided for the prevention or reversal of transplant rejection as well as therapy for autoimmune diseases.

Abstract: A method for specifically suppressing the capacity of a mammal receiving gene therapy to mount an immune response to a given expressed gene of the deficient gene in question, which response is caused by the administration of "foreign" DNA encoding an antigenic protein or vectors comprising such DNA for expression of the deficient gene in the patient receiving gene therapy.

Abstract: Disclosed is an antiallergic composition comprising, as an active ingredient, a peptide which is capable of binding to human IgE, more specifically the high-affinity immunoglobulin E receptor .alpha. chain or a soluble fragment, which is capable of binding to human IgE, or the high-affinity immunoglobulin E receptor .alpha. chain. The composition is clinically useful for blocking allergic responses.

Abstract: Pooled human immunoglobulin may be administered orally to rheumatoid arthritis patients to treat the rheumatoid arthritic condition of those patients. Oral administration of pooled human immunoglobulin can result in significant clinical improvement in the level of disease activity in patients with rheumatoid arthritis.

Abstract: The present invention relates to a method of inducing oral tolerance to ischemic injury which has the objective of minimizing the severity and size of injured regions in the brain that arise as a result of ischemia. The method responds rapidly to the onset of infarction, with treatment that is short in duration. The procedure is specifically focused on the injured area of the infarct by virtue of being targeted immunologically to the ischemic site. The method therefore avoids the possibility of inducing systemic side effects affecting other organs of the patient. The present invention involves administering myelin or a component thereof such as myelin basic protein or proteolipid protein to a subject either orally or by inhalation. The amount administered and the duration of the treatment are effective to minimize the size and severity of the infarct in the brain of the subject.

Abstract: The present invention relates to methods and compositions for the treatment and diagnosis of immune disorders, especially T helper lymphocyte-related disorders. For example, genes which are differentially expressed within and among T helper (TH) cells and TH cell subpopulations, which include, but are not limited to TH0, TH1 and TH2 cell subpopulations are identified. Genes are also identified via the ability of their gene products to interact with gene products involved in the differentiation, maintenance and effector function of such TH cells and TH cell subpopulations. The genes identified can be used diagnostically or as targets for therapeutic intervention. In this regard, the present invention provides methods for the identification and therapeutic use of compounds as treatments of immune disorders, especially TH cell subpopulation-related disorders.

Abstract: The present invention provides a method for the use of at least one serotype or a combination of serotypes of Botulinum neurotoxin either alone or in combination with other peptides or fusion proteins, that when administered in a safe and effective amount, antagonize and therefore decrease or block inflammation induced by the neurogenic mechanisms underlying or associated with inflammatory disorders, in particular, arthritis.

Abstract: Conjugates of nonimmunogenic valency platform molecules and analogs of immunogens that possess the specific B cell binding ability of the immunogen but lack T cell epitopes and which, when introduced into individuals, induce humoral anergy to the immunogen are disclosed. Accordingly, these conjugates are useful for treating antibody-mediated pathologies that are caused by foreign or self immunogens.

Abstract: A method, and compositions for use therein capable, of delivering a bioactive agent to an animal entailing the steps of encapsulating effective amounts of the agent in a biocompatible excipient to form microcapsules having a size less than approximately ten micrometers and administering effective amounts of the microcapsules to the animal. A pulsatile response is obtained, as well as mucosal and systemic immunity.

Abstract: The present invention relates to a method for the treatment of multiple sclerosis comprising administering to a patient an antibody which binds to neurotactin. Neurotactin is a membrane-anchored chemokine which is highly expressed in normal mammalian brain.

Abstract: The invention relates to methods and compositions for the treatment of autoimmune disease. Specifically, compositions comprising heat shock proteins, including gp96, hsp90, and hsp70, are disclosed. Immunotherapeutic methods for administering the hsp-containing compositions are disclosed. Furthermore, methods for preventing rejection of organs transplanted to treat autoimmune disease are disclosed. The disclosed methods are useful for treating a variety of autoimmune diseases, including insulin dependent diabetes mellitus.

Abstract: The present invention relates to a method for adjusting the affinity of a polypeptide to a target molecule by a combination of steps, including: (1) the identification of aspartyl residues which are prone to isomerization; (2) the substitution of alternative residues and screening the resulting mutants for affinity against the target molecule. In a preferred embodiment, the method of subtituting residues is affinity maturation with phage display (AMPD). In a further preferred embodiment the polypeptide is an antibody and the target molecule is an antigen. In a further preferred embodiment, the antibody is anti-IgE and the target molecule is IgE. In another embodiment, the invention relates to an anti-IgE antibody having improved affinity to IgE.

Abstract: An autoimmune vaccine is provided for administration to human patients to alleviate the symptoms of autoimmune diseases such as rheumatoid arthritis. The vaccine comprises an aliquot of the patient's blood, containing, inter alia, leukocytes having upregulated expression of various cell surface markers and lymphocytes containing decreased amounts of certain stress proteins. It is produced by subjecting the blood aliquot extracorporeally to certain stressors, namely oxidizing agents, UV radiation and elevated temperature.

Abstract: Peanuts are a common cause of food hypersensitivity reactions. The sera of 10 patients who had atopic dermatitis and a positive double-blind placebo-controlled food challenge to peanut were used to investigate the major allergens of peanut. Crude Florunner extracts were fractionated by anion-exchange chromatography using a step gradient (limit buffer, 0.05M BisTris/1.5M NaCl). One hundred microliters of each 2.0 ml fraction was dot-blotted onto nitrocellulose paper and IgE-binding activity assessed using the serum pool to select allergen-containing fractions. A protein peak (OD 280) which eluted at 10% NaCl and demonstrated intense IgE-binding was further analyzed by two-dimensional SDS-PAGE/immunoblot analysis. The majority of this fraction is a protein which has a molecular weight of 17 kD and a pI of 5.2. Sequencing data from the N-terminus revealed the following initial 9 amino acids: (*)-Q-Q-(*)-E-L-Q-D-L.

Abstract: The invention identifies the CTLA4 receptor as a ligand for the B7 antigen. The complete amino acid sequence encoding human CTLA4 receptor gene is provided. Methods are provided for expressing CTLA4 as an immunoglobulin fusion protein, for preparing hybrid CTLA4 fusion proteins, and for using the soluble fusion proteins, fragments and derivatives thereof, including monoclonal antibodies reactive with B7 and CTLA4, to regulate T cell interactions and immune responses mediated by such interactions.

Abstract: Disclosed is a method for reducing an immune response to a parenterally administered non-autologous antigen in an individual who is immunologically responsive thereto by mucosally administering to the individual an amount of the antigen effective to reduce any immune response to parenteral administration of said antigen. The antigen can be a polypeptide such as a hormone, like insulin, which supplements a metabolic deficiency in the recipient of a polypeptide intended to serve the same function. The polypeptide can also be one which supplements a deficiency in the production of a physiologically important polypeptide, such as a hematologic regulatory factor. The hematologic regulatory factor can enhance or inhibit thrombogenesis or platelet deposition. Also, the antigen can be a tissue or cell preparation, such as of allogeneic or xenogeneic tissue or cells.

Abstract: The subject invention concerns novel materials and methods for the treatment and/or prevention of autoimmune disease. In a specific embodiment, elevated production of prostaglandin synthase-2 (PGS-2) is correlated with autoimmune dysfunction.

Abstract: A combination of a mucosally administrable bystander antigen and an orally, enterally, or parenterally administrable methotrexate is employed to make a pharmaceutical formulation and to treat or prevent autoimmune disease.

Abstract: A transdermal liposome system delivers antigen to immune cells without perforation of the skin, and induces an immune response in an animal or human. The system uses liposomes to deliver a variety of antigens which can elicit an antigen-specific immune response (e.g., humoral and/or cellular effectors) after topical application of a formulation containing liposomes and antigen to intact skin of the animal or human.

Abstract: Methods for inhibiting synovial cell growth and treating chronic rheumatoid arthritis are provided. The methods comprise administering a pharmaceutical composition comprising an interleukin-6 antagonist, such as an anti-IL-6 receptor antibody, and a physiologically acceptable carrier.

Abstract: Donor tissue containing antigen-presenting cells (APCs) can be modified to reduce rejection when the donor tissue is used as an allograft by exposing the donor tissue which has been treated with a photosensitizing agent having an absorption maximum between 400-900 nm to a wavelength absorbed by the photosensitizing agent so as to attenuate the APCs in the donor tissue but wherein the light is not cytotoxic to the APCs.

Abstract: The present invention comprises a simple way of identifying the tendency towards allergy or allergy already broken out, and showing the probability of allergy in a patient, by measuring the receptor expression of the phagocytic cells of peripheral blood. With a logistic regression model a combination of variables were found which best describe the probability of allergy. Thus the invention relates to a method for detecting allergy and a test kit for accomplishing the method. The invention also relates to a sensitive and specific logistic model for determining the probability of allergy.