Histamine-releasing factor (hrf), hrf-receptor and methods of modulating inflammation

Abstract

Methods of treating a food allergy, allergic reactions, hypersensitivity, inflammatory responses, inflammation are provided. In one method, histamine releasing factor (HRF)/translationally controlled tumor protein (TCTP) is contacted with a compound that inhibits or reduces binding of HRF/TCTP to an immunoglobulin in order to treat the food allergy, allergic reaction, hypersensitivity, inflammatory response, or inflammation. Methods of reducing or decreasing the probability, severity, frequency, duration or preventing a subject from having an acute or chronic food allergy, allergic reaction, hypersensitivity, an inflammatory response or inflammation, are also provided. In one method, histamine releasing factor (HRF)/translationally controlled tumor protein (TCTP) is contacted with a compound that inhibits or reduces binding of HRF/TCTP to an immunoglobulin in order to reduce or decrease the probability, severity, frequency, duration or prevent a subject from having an acute or chronic food allergy, allergic reaction, hypersensitivity, an inflammatory response or inflammation.

1 . (canceled) 
     
     
         2 . A method of treating an allergic reaction, hypersensitivity, an inflammatory response or inflammation, comprising contacting histamine releasing factor (HRF)/translationally controlled tumor protein (TCTP) with a compound that inhibits or reduces binding of HRF/TCTP to an immunoglobulin thereby treating the allergic reaction, hypersensitivity, inflammatory response or inflammation. 
     
     
         3 . (canceled) 
     
     
         4 . The method of  claim 2 , wherein the compound comprises a peptide or polypeptide. 
     
     
         5 . The method of  claim 4 , wherein the peptide or polypeptide comprises an antibody or an antibody subsequence that binds to HRF/TCTP. 
     
     
         6 . The method of  claim 5 , wherein the antibody or antibody subsequence is human or humanized. 
     
     
         7 . The method of  claim 5 , wherein the antibody or antibody subsequence is monoclonal. 
     
     
         8 . The method of  claim 5 , wherein the antibody or antibody subsequence competes for binding of an antibody set forth in Tables 2 or 3 for binding to the HRF/TCTP. 
     
     
         9 . The method of  claim 5 , wherein the antibody or antibody subsequence binds to an epitope of HRF/TCTP to which an antibody set forth in Tables 2 or 3 binds. 
     
     
         10 . The method of  claim 5 , wherein the antibody or antibody subsequence has a binding affinity (Kd) for binding to HRF/TCTP of about 10 −5  to about 10 −13  M. 
     
     
         11 .- 12 . (canceled) 
     
     
         13 . The method of claim  12 , wherein the IgG or IgA isotype is selected from IgG1, IgG2, IgG3, and IgG4; and IgA1 and IgA2. 
     
     
         14 . The method of  claim 5 , wherein the antibody subsequence is selected from Fab, Fab′, F(ab′) 2 , Fv, Fd, single-chain Fv (scFv), disulfide-linked Fvs (sdFv), light chain variable region V L , heavy chain variable region V H , trispecific (Fab 3 ), bispecific (Fab 2 ), diabody ((V L -V H ) 2  or (V H -V L ) 2 ), triabody (trivalent), tetrabody (tetravalent), minibody ((scF V -C H ) 2 ), bispecific single-chain Fv (Bis-scFv), IgGdeltaCH 2 , scFv-Fc, (scFv) 2 -Fc and IgG4PE. 
     
     
         15 . The method of  claim 4 , wherein the HRF/TCTP polypeptide, or a fragment of an HRF/TCTP polypeptide comprises a fusion or chimeric polypeptide. 
     
     
         16 .- 17 . (canceled) 
     
     
         18 . The method of  claim 4 , wherein the peptide or polypeptide comprises an HRF/TCTP polypeptide, or a fragment of an HRF/TCTP polypeptide that binds to an immunoglobulin. 
     
     
         19 . The method of  claim 15  or  18 , wherein the fragment of HRF/TCTP polypeptide that binds to an immunoglobulin comprises or consists of amino acids 1-19 or amino acids 79-142 of a mammalian HRH/TCTP sequence. 
     
     
         20 .- 22 . (canceled) 
     
     
         23 . The method of  claim 2 , wherein the food allergy, allergic reaction, hypersensitivity, inflammatory response or inflammation is chronic or acute. 
     
     
         24 . (canceled) 
     
     
         25 . The method of  claim 2 , wherein the treatment is sufficient to decrease, reduce, inhibit, suppress, limit, control or improve the probability, severity, frequency, or duration of one or more adverse symptoms, disorders, illnesses, pathologies, diseases, or complications caused by or associated with the food allergy, allergic reaction, hypersensitivity, inflammatory response or inflammation. 
     
     
         26 . The method of  claim 2 , wherein the method reduces or inhibits progression, severity, frequency, duration or probability of an adverse symptom of the food allergy, allergic reaction, hypersensitivity, inflammatory response or inflammation. 
     
     
         27 . (canceled) 
     
     
         28 . The method of  claim 2 , wherein the allergic reaction is selected from: Extrinsic or intrinsic bronchial asthma; Allergic rhinitis; Onchocercal dermatitis; Atopic dermatitis; eczema; rash; allergic urticaria (e.g. hives); allergic conjunctivitis; Drug reactions; Nodules, eosinophilia, rheumatism, dermatitis, and swelling (NERDS); Eosophageal and a gastrointestinal allergy. 
     
     
         29 . The method of  claim 2 , wherein the hypersensitivity, inflammatory response or inflammation comprises a respiratory disease or disorder. 
     
     
         30 . (canceled) 
     
     
         31 . The method of  claim 29 , wherein the respiratory disease or disorder comprises asthma, allergic asthma, bronchiolitis or pleuritis. 
     
     
         32 . The method of  claim 29 , wherein the respiratory disease or disorder is selected from: Airway Obstruction, Apnea, Asbestosis, Atelectasis, Berylliosis, Bronchiectasis, Bronchiolitis, Bronchiolitis Obliterans Organizing Pneumonia, Bronchitis, Bronchopulmonary Dysplasia, Empyema, Pleural Empyema, Pleural Epiglottitis, Hemoptysis, Hypertension, Kartagener Syndrome, Meconium Aspiration, Pleural Effusion, Pleurisy, Pneumonia, Pneumothorax, Respiratory Distress Syndrome, Respiratory Hypersensitivity, Rhinoscleroma, Scimitar Syndrome, Severe Acute Respiratory Syndrome, Silicosis, Tracheal Stenosis, eosinophilic pleural effusions, Histiocytosis; chronic eosinophilic pneumonia; hypersensitivity pneumonitis; Allergic bronchopulmonary aspergillosis; Sarcoidosis; Idiopathic pulmonary fibrosis; pulmonary edema; pulmonary embolism; pulmonary emphysema; Pulmonary Hyperventilation; Pulmonary Alveolar Proteinosis; Chronic Obstructive Pulmonary Disease (COPD); Interstitial Lung Disease; allergic rhinoconjunctivitis; allergic conjunctivitis and Topical eosinophilia. 
     
     
         33 . The method of  claim 2 , wherein the allergic reaction, hypersensitivity, inflammatory response or inflammation affects the skin or eye. 
     
     
         34 . A method of increasing, enhancing or stimulating airway-dilation, comprising administering to a subject in need of increasing airway-dilation an amount of a compound that inhibits or reduces binding of HRF/TCTP to an immunoglobulin sufficient to increase, enhance or stimulate airway-dilation in the subject. 
     
     
         35 . (canceled) 
     
     
         36 . The method of  claim 1  or  34 , wherein the compound is administered prior to, substantially contemporaneously with or following one or more adverse symptoms, disorders, illnesses, pathologies, diseases, or complications caused by or associated with the food allergy, allergic reaction or hypersensitivity. 
     
     
         37 . The method of  claim 1  or  34 , further comprising administering a second drug. 
     
     
         38 .- 39 . (canceled) 
     
     
         40 . The method of  claim 1  or  34 , wherein the compound is administered via ingestion, via inhalation, or topically. 
     
     
         41 .- 62 . (canceled) 
     
     
         63 . An isolated or purified antibody or antibody subsequence that binds to mammalian HRF/TCTP sequence comprising or consisting of amino acids 1-19 (MIIYRDLISHDEMFSDIYK, SEQ ID NO:1) or amino acids 79-142 (QETSFTKEAYKKYIKDYMKSIKGKLEEQRPERVKPFMTGAAEQIKHILANEKNYQFF IGENMNP, SEQ ID NO:2). 
     
     
         64 . The antibody or subsequence of  claim 63 , wherein the fragment of mammalian HRF/TCTP sequence comprises or consists of: MIIYRDLISHDEMFSDIYKIREIADGLCLEVEGKMVSRTEGNIDDSLIGGNASAEGPEG EGTESTVITGVDIVMNHHLQETSFTKEAYKKYIKDYMKSIKGKLEEQRPERVKPFMT GAAEQIKHILANFKNYQFFIGENMNPDGMVALLDYREDGVTPYMIFFKDGLEMEKC (SEQ ID NO:3), or a fragment 5-171 amino acid residues in length. 
     
     
         65 .- 71 . (canceled)