Compositions and methods for treating or preventing lupus

Abstract

The present disclosure provides methods for inhibiting and/or reducing self-reactive IgE and/or basophils, thereby treating or preventing lupus, lupus nephritis, and lupus-related disorders.

1 - 18 . (canceled) 
     
     
         19 . A method of inhibiting or reducing the development or progression to lupus nephritis in a subject in need thereof, the method comprising administering to the subject an effective amount of a small molecule that reduces the expression or biological activity of IgE or an IgE receptor in the subject,
 wherein the small molecule is a Syk kinase inhibitor; and   wherein the small molecule effectuates the inhibition and/or reduction in the development and/or progression to lupus nephritis.   
     
     
         20 . The method of  claim 19 , wherein the small molecule that is administered is fostamatinib. 
     
     
         21 . The method of  claim 19 , wherein the method reduces at least one of: the level of autoreactive IgEs, the level of circulating immune complexes, basophil activation, or a combination thereof. 
     
     
         22 . The method of  claim 19 , wherein the subject has elevated IgE levels. 
     
     
         23 . The method of  claim 19 , wherein the method further comprises administering to the subject an agent selected from the group consisting of nonsteroidal anti-inflammatory drugs (NSAIDs), hydroxychloroquine, corticosteroids, cyclophosphamide, azthioprine, methotrexate, mycophenolate, belimumab, dehydroepiandrosterone, and rituximab. 
     
     
         24 . A method of reducing or inhibiting the development or progression to lupus nephritis in a subject in need thereof, the method comprising administering to the subject an effective amount of a small molecule that decreases the number or activity of basophils or that reduces basophil activation in the subject,
 wherein the small molecule is a Syk kinase inhibitor; and   wherein the small molecule effectuates the reduction and/or inhibition of the development and/or progression to lupus nephritis.   
     
     
         25 . The method of  claim 24 , wherein the method reduces levels of one or more of CD203c expression, CD62L, and HLA-DR in said subject. 
     
     
         26 . The method of  claim 24 , wherein the small molecule that is administered is fostamatinib. 
     
     
         27 . The method of  claim 24 , wherein the method further comprises administering to the subject an agent selected from the group consisting of nonsteroidal anti-inflammatory drugs (NSAIDs), hydroxychloroquine, corticosteroids, cyclophosphamide, azthioprine, methotrexate, mycophenolate, belimumab, dehydroepiandrosterone, and rituximab. 
     
     
         28 . A method of treating lupus nephritis in a subject in need thereof, the method comprising administering to the subject an effective amount of a small molecule that reduces the expression or biological activity of IgE or an IgE receptor in the subject,
 wherein the small molecule is a Syk kinase inhibitor; and   wherein the small molecule effectuates the amelioration of lupus nephritis.   
     
     
         29 . The method of  claim 28 , wherein the method reduces at least one of: the level of autoreactive IgEs, the level of circulating immune complexes, basophil activation, or a combination thereof. 
     
     
         30 . The method of  claim 28 , wherein the subject has elevated IgE levels. 
     
     
         31 . The method of  claim 28 , wherein the small molecule that is administered is fostamatinib. 
     
     
         32 . The method of  claim 28 , wherein the method further comprises administering to the subject an agent selected from the group consisting of nonsteroidal anti-inflammatory drugs (NSAIDs), hydroxychloroquine, corticosteroids, cyclophosphamide, azthioprine, methotrexate, mycophenolate, belimumab, dehydroepiandrosterone, and rituximab. 
     
     
         33 . A method of treating lupus nephritis in a subject in need thereof, the method comprising administering to the subject an effective amount of a small molecule that decreases the number or activity of basophils or that reduces basophil activation in the subject,
 wherein the small molecule is a Syk kinase inhibitor; and   wherein the small molecule effectuates the amelioration of lupus nephritis.   
     
     
         34 . The method of  claim 33 , wherein the method reduces levels of one or more of CD203c expression, CD62L, and HLA-DR in said subject. 
     
     
         35 . The method of  claim 33 , wherein the small molecule that is administered is fostamatinib. 
     
     
         36 . The method of  claim 33 , wherein the method further comprises administering to the subject an agent selected from the group consisting of nonsteroidal anti-inflammatory drugs (NSAIDs), hydroxychloroquine, corticosteroids, cyclophosphamide, azthioprine, methotrexate, mycophenolate, belimumab, dehydroepiandrosterone, and rituximab.