Methods for treating and diagnosing systemic lupus erythematosus

Abstract

Methods and reagents for diagnosing, prognosing, and treating systemic lupus erythematosus (SLE) are disclosed, involving calculating an SLE risk score for a subject based on a level of each of an erythrocyte C4d (EC4d) marker, a B-cell C4d (BC4d) marker, anti-nuclear antibodies (ANA), and optional rule-out markers.

What is claimed is: 
     
         1 . A method for treating systemic lupus erythematosus in a human subject in need thereof, the method comprising:
 (a) measuring a level of erythrocyte-bound C4d (EC4d) marker and a level of B-lymphocyte-bound C4d (BC4d) marker in a blood sample obtained from the human subject;   (b) measuring a level of a marker selected from the group consisting of anti-Sjogren's syndrome type B antigen antibody, anti-Scl-70 antibody, anti-Jo-1 antibody, and anti-centromere protein B antibody in the blood sample obtained from the human subject; and   (c) administering to the human subject an effective amount of cyclophosphamide, a corticosteroid, methotrexate, azathioprine, leflunomide, belimumab, or hydroxychloroquine, thereby treating systemic lupus erythematosus.   
     
     
         2 . The method of  claim 1 , further comprising measuring a level of anti-nuclear antibody (ANA) in the blood sample obtained from the human subject. 
     
     
         3 . The method of  claim 1 , wherein step (b) comprises measuring a level of two markers selected from the group consisting of anti-Sjogren's syndrome type B antigen antibody, anti-Scl-70 antibody, anti-Jo-1 antibody, and anti-centromere protein B antibody. 
     
     
         4 . The method of  claim 1 , wherein step (b) comprises measuring a level of three markers selected from the group consisting of anti-Sjogren's syndrome type B antigen antibody, anti-Scl-70 antibody, anti-Jo-1 antibody, and anti-centromere protein B antibody. 
     
     
         5 . The method of  claim 1 , wherein step (b) comprises measuring a level of anti-Sjogren's syndrome type B antigen antibody, anti-Scl-70 antibody, anti-Jo-1 antibody, and anti-centromere protein B antibody. 
     
     
         6 . The method of  claim 1 , wherein the human subject is negative for systemic lupus erythematosus based on a level of double-stranded DNA antibody. 
     
     
         7 . The method of  claim 1 , further comprising measuring a level of double-stranded DNA antibody in the blood sample obtained from the human subject; wherein the human subject is negative for systemic lupus erythematosus based on the level of double-stranded DNA antibody. 
     
     
         8 . The method of  claim 1 , wherein the human subject is negative for systemic lupus erythematosus based on a level of anti-Smith antibody. 
     
     
         9 . The method of  claim 1 , further comprising measuring a level of anti-Smith antibody in the blood sample obtained from the human subject; wherein the human subject is negative for systemic lupus erythematosus based on the level of anti-Smith antibody. 
     
     
         10 . The method of  claim 1 , wherein the human subject is negative for systemic lupus erythematosus based on the level of EC4d marker. 
     
     
         11 . The method of  claim 1 , wherein the human subject is negative for systemic lupus erythematosus based on the level of BC4d marker. 
     
     
         12 . The method of  claim 1 , wherein the human subject is negative for systemic lupus erythematosus based on individual levels of double-stranded DNA antibody, anti-Smith antibody, EC4d marker, and BC4d marker. 
     
     
         13 . The method of  claim 1 , wherein measuring the level of EC4d marker comprises measuring the level of EC4d on the surface of erythrocytes; and wherein measuring the level of BC4d marker comprises measuring the level of BC4d on the surface of B lymphocytes. 
     
     
         14 . The method of  claim 1 , wherein the level of the marker is measured by enzyme-linked immunosorbent assay, indirect immunofluorescence, radioimmunoassay, or flow cytometry. 
     
     
         15 . A method for treating systemic lupus erythematosus in a human subject in need thereof, the method comprising:
 (a) measuring a level of erythrocyte-bound C4d (EC4d) marker, a level of B-lymphocyte-bound C4d (BC4d) marker, and a level of anti-nuclear antibody (ANA) in a blood sample obtained from the human subject;   (b) administering to the human subject an effective amount of cyclophosphamide, a corticosteroid, methotrexate, azathioprine, leflunomide, belimumab, or hydroxychloroquine, thereby treating systemic lupus erythematosus;   wherein the human subject is negative for systemic lupus erythematosus based on individual levels of double-stranded DNA antibody and anti-Smith antibody.   
     
     
         16 . The method of  claim 15 , wherein the human subject is negative for systemic lupus erythematosus based on individual levels of double-stranded DNA antibody, anti-Smith antibody, EC4d marker, and BC4d marker. 
     
     
         17 . The method of  claim 15 , wherein measuring the level of EC4d marker comprises measuring the level of EC4d on the surface of erythrocytes; and wherein measuring the level of BC4d marker comprises measuring the level of BC4d on the surface of B lymphocytes. 
     
     
         18 . The method of  claim 15 , wherein the level of the EC4d marker, BC4d marker, and ANA is measured by enzyme-linked immunosorbent assay, indirect immunofluorescence, radioimmunoassay, or flow cytometry. 
     
     
         19 . A method for treating systemic lupus erythematosus in a human subject in need thereof, the method comprising:
 (a) measuring a level of erythrocyte-bound C4d (EC4d) marker, a level of B-lymphocyte-bound C4d (BC4d) marker, and a level of anti-nuclear antibody (ANA) in a blood sample obtained from the human subject;   (b) measuring a level of a marker selected from the group consisting of anti-Sjogren's syndrome type B antigen antibody, anti-Scl-70 antibody, anti-Jo-1 antibody, and anti-centromere protein B antibody in the blood sample obtained from the human subject; and   (c) administering to the human subject an effective amount of cyclophosphamide, a corticosteroid, methotrexate, azathioprine, leflunomide, belimumab, or hydroxychloroquine, thereby treating systemic lupus erythematosus;   wherein the human subject is negative for systemic lupus erythematosus based on a level of double-stranded DNA antibody.   
     
     
         20 . The method of  claim 19 , wherein the human subject is negative for systemic lupus erythematosus based on a level of anti-Smith antibody. 
     
     
         21 . The method of  claim 19 , further comprising measuring a level of anti-Smith antibody in the blood sample obtained from the human subject; wherein the human subject is negative for systemic lupus erythematosus based on the level of anti-Smith antibody. 
     
     
         22 . The method of  claim 19 , wherein the level of the EC4d marker, BC4d marker, and ANA is measured by enzyme-linked immunosorbent assay, indirect immunofluorescence, radioimmunoassay, or flow cytometry; and wherein the level of the marker in (b) is measured by enzyme-linked immunosorbent assay, indirect immunofluorescence, radioimmunoassay, or flow cytometry. 
     
     
         23 . The method of  claim 1 , further comprising adjusting the level of the EC4d marker, the level of the BC4d marker, and the level of the marker selected from the group consisting of anti-Sjogren's syndrome type B antigen antibody, anti-Scl-70 antibody, anti-Jo-1 antibody, and anti-centromere protein B antibody by a transformation analysis. 
     
     
         24 . The method of  claim 15 , further comprising adjusting the level of the EC4d marker, the level of the BC4d marker, and the level of anti-nuclear antibody (ANA) by a transformation analysis. 
     
     
         25 . The method of  claim 19 , further comprising adjusting the level of the EC4d marker, the level of the BC4d marker, the level of ANA, and the level of the marker selected from the group consisting of anti-Sjogren's syndrome type B antigen antibody, anti-Scl-70 antibody, anti-Jo-1 antibody, and anti-centromere protein B antibody by a transformation analysis.