Methods for use with baff antagonists

Abstract

BAFF plays a central role in acquired immunity. The disclosure identifies BAFF responsive genes that are substantially upregulated by administration of BAFF and substantially downregulated by treatment with a BAFF antagonist. Specific genes are NF-κB2, CD23, H2-Mβ (the beta chain of H2-DM), Fig-1, and OBF-1. The disclosure provides methods and compositions for monitoring the activity of a BAFF antagonist in a mammal; monitoring BAFF activity in a mammal; identifying a mammal to be treated with a BAFF antagonist; and related uses. Such methods include detecting one or more molecules selected from the group consisting of Fig-1 molecule, OBF-1 molecule, and H2-Mβ molecule in a biological sample of the mammal, and optionally further detecting NF-κB2 molecule and/or CD23 molecule in the biological sample.

1 - 2 . (canceled) 
     
     
         3 . A method for monitoring efficacy of a BAFF antagonist in a mammal comprising the steps of administering the BAFF antagonist to the mammal and detecting at the transcriptional and/or translational level one or both molecules selected from the group consisting of NF-κB2 molecule and CD23 molecule in a biological sample of the treated mammal, wherein the level of expression, relative to a control, of at least one of the detected molecules indicates efficacy of the BAFF antagonist in the mammal. 
     
     
         4 . The method of  claim 3 , further comprising the step of detecting at the transcriptional and/or translational level(s) one or more molecules selected from the group consisting of Fig-1 molecule, OBF-1 molecule, and H2-Mβ molecule in a biological sample of the treated mammal, wherein the level of expression, relative to a control, of at least one of the detected molecules indicates efficacy of the BAFF antagonist in the mammal. 
     
     
         5 . A method for monitoring BAFF activity in a mammal, comprising the step of detecting at the transcriptional and/or translational level(s) in a biological sample of the mammal one or more molecules selected from the group consisting of H2-Mβ molecule, Fig-1 molecule, OBF-1 molecule, wherein elevated expression, relative to a control, of at least one of the detected molecules indicates elevated BAFF activity. 
     
     
         6 . The method according to  claim 5 , wherein the method further comprises the step of detecting at the transcriptional and/or translational level(s) one or more molecules selected from the group consisting of NF-κB2 molecule and CD23 molecule in a biological sample of the mammal. 
     
     
         7 . A method for monitoring BAFF activity in a mammal, comprising the step of detecting at the transcriptional level in a biological sample of the mammal one or both molecules selected from the group consisting of NF-κB2 molecule and CD23 molecule, wherein elevated expression, relative to a control, of at least one of the detected molecules indicates elevated BAFF activity in the mammal. 
     
     
         8 . The method of  claim 7 , further comprising the step of detecting at the transcriptional and/or translational level(s) in a biological sample one or more molecules selected from the group consisting of H2-Mβ molecule, Fig-1 molecule, OBF-1 molecule, wherein elevated expression, relative to a control, of at least one of the detected molecules indicates elevated BAFF activity. 
     
     
         9 . A method of identifying a mammal treated or to be treated with a BAFF antagonist, comprising the step of providing a sample from a mammal and detecting one at the transcriptional and/or translational level(s) or more molecules selected from the group consisting of Fig-1 molecule, OBF-1 molecule, and H2-Mβ molecule in the sample of the mammal, wherein elevated expression, relative to a control, of at least one of the detected molecules indicates that the mammal should be treated with the BAFF antagonist. 
     
     
         10 . A method of identifying a mammal treated or to be treated with a BAFF antagonist, comprising the steps of providing a biological sample from a mammal and detecting at the transcriptional level in a biological sample of the mammal one or both molecules selected from the group consisting of NF-κB2 molecule and CD23 molecule, wherein elevated expression, relative to a control, of at least one of the detected molecules indicates that the mammal should be treated with the BAFF antagonist. 
     
     
         11 . The method of  claim 10 , further comprising detecting one at the transcriptional and/or translational level(s) or more molecules selected from the group consisting of Fig-1 molecule, OBF-1 molecule, and H2-Mβ molecule in the sample of the mammal, wherein elevated expression, relative to a control, of at least one of the detected molecules indicates that the mammal should be treated with the BAFF antagonist. 
     
     
         12 . The method according to  claim 3 , wherein the mammal is suffering from an autoimmune disease. 
     
     
         13 . The method according to  claim 12 , wherein the autoimmune disease is selected from the group consisting of autoimmune disease is rheumatoid arthritis, lupus, and Sjogren's disease. 
     
     
         14 . The method according to  claim 3 , wherein the mammal is suffering from a hyperproliferative immune disorder. 
     
     
         15 . The method according to  claim 14 , wherein the hyperproliferative immune disorder is a B cell hyperproliferative disorder. 
     
     
         16 . The method according to  claim 15 , wherein the hyperproliferative disorder is selected from the group consisting of NHL, CLL, ALL, FL, and multiple myeloma. 
     
     
         17 . The method according to  claim 3 , further comprising the step of detecting BAFF molecule in the biological sample. 
     
     
         18 . The method according to  claim 3 , further comprising the step of detecting BR3 molecules in the biological sample. 
     
     
         19 . The method according to  claim 3 , wherein the mammal is human. 
     
     
         20 . The method according to  claim 3 , wherein the OBF-1 molecule is selected from:
 (a) a polypeptide comprising a sequence selected from SEQ ID NO:11 and SEQ ID NO:16; and   (b) an mRNA comprising a nucleotide sequence encoding an amino acid sequence selected from SEQ ID NO:11 and SEQ ID NO:16.   
     
     
         21 - 25 . (canceled) 
     
     
         26 . The method according to  claim 3 , wherein the BAFF antagonist is selected from the group consisting of anti-BAFF antibody, antibody against one or more BAFF receptors, dominant negative BAFF, and a soluble BAFF receptor. 
     
     
         27 . The method according to  claim 26 , wherein the BAFF antagonist comprises a sequence selected from the group consisting of:
 (a) amino acids 1-73 of SEQ ID NO:21;   (b) SEQ ID NO:22;   (c) SEQ ID NO:26;   (d) SEQ ID NO:24;   (e) SEQ ID NO:25;   (f) amino acids 8-41 of SEQ ID NO:27; and   (g) amino acids 1-100 of SEQ ID NO:28.   
     
     
         28 - 56 . (canceled)