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US 11,531,033 B2Granted
Methods for treating and diagnosing systemic lupus erythematosus
AssigneeExagen Inc.
InventorsThierry Dervieux, Derren Barken
Life of this patent
Estimating the term…
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, antinuclear antibodies (ANA), anti-Smith antibodies (anti-Sm) and optional rule-out markers (SS-B/La, Scl-70, Jo-1, CENP, MCV).
Claims14
A method of treating systemic lupus erythematosus (SLE) in a subject identified as having SLE based on a systemic lupus erythematosus risk score, the method comprising:
- (A) determining a level of erythrocyte C4d marker, a level of B-cell C4d marker, a level of anti-nuclear antibody, a level of anti-Sjögren's syndrome type B antigen antibody, a level of anti-Scl-70 antibody, a level of anti-Jo-1 antibody, and a level of anti-centromere protein B antibody in a blood sample from the subject;
- (B) calculating a systemic lupus erythematosus index score with the level of the erythrocyte C4d marker, the level of the B-cell C4d marker, the level of the anti-nuclear antibody, the level of anti-Sjögren's syndrome type B antigen antibody, the level of anti-Scl-70 antibody, the level of anti-Jo-1 antibody, and the level of anti-centromere protein B antibody with the equation:
- Index=−5.2626+0.9877×ANAComp+[0.2955×log(EC4d)+1.0260×log(BC4d)]−2.4944×SpecComp;
- wherein:
- (i) Index is the systemic lupus erythematosus index score;
- (ii) ANAComp is:
- (a) 0, when the level of anti-nuclear antibody <20 units, as measured by an enzyme-linked immunosorbent assay;
- (b) 1, when the level of anti-nuclear antibody is ≥20 units and <60 units, as measured by an enzyme-linked immunosorbent assay;
- or
- (c) 2, when the level of anti-nuclear antibody ≥60 units, as measured by an enzyme-linked immunosorbent assay;
- (iii) log is natural log;
- (iv) EC4d is net mean fluorescence intensity of erythrocyte C4d marker, as measured by fluorescence activated flow cytometry;
- (v) BC4d is net mean fluorescence intensity of B-cell C4d marker, as measured by fluorescence activated flow cytometry;
- and
- (vi) SpecComp is:
- (a) 0, when the level of anti-Sjögren's syndrome type B antigen antibody is ≤10 Units/mL;
- the level of anti-Scl-70 antibody is ≤10 Units/mL;
- the level of anti-Jo-1 antibody is ≤10 Units/mL;
- and the level of anti-centromere protein B antibody is ≤10 Units/mL;
- where each are as measured by a fluoroenzymatic immunoassay;
- (b) 1, when one or more of the level of anti-Sjögren's syndrome type B antigen antibody is >10 Units/mL;
- the level of anti-Scl-70 antibody >10 Units/mL;
- the level of anti-Jo-1 antibody is >10 Units/mL;
- or the level of anti-centromere protein B antibody is >10 Units/mL;
- where each are as measured by a fluoroenzymatic immunoassay;
- (C) identifying the subject as having SLE when the index score is >0;
- and
- (D) treating the subject identified as having SLE in step (C) with an effective amount of belimumab.
25 more elements
A method of treating systemic lupus erythematosus (SLE) in a subject identified as having SLE based on a systemic lupus erythematosus risk score, the method comprising:
- (A) determining a level of erythrocyte C4d marker, a level of B-cell C4d marker, a level of anti-nuclear antibody, a level of anti-Sjögren's syndrome type B antigen antibody, a level of anti-Scl-70 antibody, a level of anti-Jo-1 antibody, and a level of anti-centromere protein B antibody in a blood sample from the subject;
- (B) calculating a systemic lupus erythematosus index score with the level of the erythrocyte C4d marker, the level of the B-cell C4d marker, the level of the anti-nuclear antibody, the level of anti-Sjögren's syndrome type B antigen antibody, the level of anti-Scl-70 antibody, the level of anti-Jo-1 antibody, and the level of anti-centromere protein B antibody with the equation:
- Index=−5.2626+0.9877×ANAComp[0.2955×log(EC4d)+1.0260×log(BC4d)]−2.4944×SpecComp;
- wherein:
- (i) Index is the systemic lupus erythematosus index score;
- (ii) ANAComp is:
- (a) 0, when the level of anti-nuclear antibody <20 units, as measured by an enzyme-linked immunosorbent assay;
- (b) 1, when the level of anti-nuclear antibody is ≥20 units and <60 units, as measured by an enzyme-linked immunosorbent assay;
- or
- (c) 2, when the level of anti-nuclear antibody ≥60 units, as measured by an enzyme-linked immunosorbent assay;
- (iii) log is natural log;
- (iv) EC4d is net mean fluorescence intensity of erythrocyte C4d marker, as measured by fluorescence activated flow cytometry;
- (v) BC4d is net mean fluorescence intensity of B-cell C4d marker, as measured by fluorescence activated flow cytometry;
- and
- (vi) SpecComp is:
- (a) 0, when the level of anti-Sjögren's syndrome type B antigen antibody is ≤10 Units/mL;
- the level of anti-Scl-70 antibody is ≤10 Units/mL;
- the level of anti-Jo-1 antibody is ≤10 Units/mL;
- and the level of anti-centromere protein B antibody is ≤10 Units/mL;
- where each are as measured by a fluoroenzymatic immunoassay;
- (b) 1, when one or more of the level of anti-Sjögren's syndrome type B antigen antibody is >10 Units/mL;
- the level of anti-Scl-70 antibody >10 Units/mL;
- the level of anti-Jo-1 antibody is >10 Units/mL;
- or the level of anti-centromere protein B antibody is >Units/mL;
- where each are as measured by a fluoroenzymatic immunoassay;
- (C) identifying the subject as having SLE when the index score is >0;
- and
- (D) treating the subject identified as having SLE in step (C) with an effective amount of cyclophosphami de.
25 more elements
A method of treating systemic lupus erythematosus (SLE) in a subject identified as having SLE based on a systemic lupus erythematosus risk score, the method comprising:
- (A) determining a level of erythrocyte C4d marker, a level of B-cell C4d marker, a level of anti-nuclear antibody, a level of anti-Sjögren's syndrome type B antigen antibody, a level of anti-Scl-70 antibody, a level of anti-Jo-1 antibody, and a level of anti-centromere protein B antibody in a blood sample from the subject;
- (B) calculating a systemic lupus erythematosus index score with the level of the erythrocyte C4d marker, the level of the B-cell C4d marker, the level of the anti-nuclear antibody, the level of anti-Sjögren's syndrome type B antigen antibody, the level of anti-Scl-70 antibody, the level of anti-Jo-1 antibody, and the level of anti-centromere protein B antibody with the equation:
- Index=−5.2626+0.9877×ANAComp[0.2955×log(EC4d)+1.0260×log(BC4d)]−2.4944×SpecComp;
- wherein:
- (i) Index is the systemic lupus erythematosus index score;
- (ii) ANAComp is:
- (a) 0, when the level of anti-nuclear antibody <20 units, as measured by an enzyme-linked immunosorbent assay;
- (b) 1, when the level of anti-nuclear antibody is ≥20 units and <60 units, as measured by an enzyme-linked immunosorbent assay;
- or
- (c) 2, when the level of anti-nuclear antibody ≥60 units, as measured by an enzyme-linked immunosorbent assay;
- (iii) log is natural log;
- (iv) EC4d is net mean fluorescence intensity of erythrocyte C4d marker, as measured by fluorescence activated flow cytometry;
- (v) BC4d is net mean fluorescence intensity of B-cell C4d marker, as measured by fluorescence activated flow cytometry;
- and
- (vi) SpecComp is:
- (a) 0, when the level of anti-Sjögren's syndrome type B antigen antibody is ≤10 Units/mL;
- the level of anti-Scl-70 antibody is ≤10 Units/mL;
- the level of anti-Jo-1 antibody is ≤10 Units/mL;
- and the level of anti-centromere protein B antibody is ≤10 Units/mL;
- where each are as measured by a fluoroenzymatic immunoassay;
- (b) 1, when one or more of the level of anti-Sjögren's syndrome type B antigen antibody is >10 Units/mL;
- the level of anti-Scl-70 antibody >10 Units/mL;
- the level of anti-Jo-1 antibody is >10 Units/mL;
- or the level of anti-centromere protein B antibody is >10 Units/mL;
- where each are as measured by a fluoroenzymatic immunoassay;
- (C) identifying the subject as having SLE when the index score is >0;
- and
- (D) treating the subject identified as having SLE in step (C) with an effective amount of methotrexate.
25 more elements
A method of treating systemic lupus erythematosus (SLE) in a subject identified as having SLE based on a systemic lupus erythematosus risk score, the method comprising:
- (A) determining a level of erythrocyte C4d marker, a level of B-cell C4d marker, a level of anti-nuclear antibody, a level of anti-Sjögren's syndrome type B antigen antibody, a level of anti-Scl-70 antibody, a level of anti-Jo-1 antibody, and a level of anti-centromere protein B antibody in a blood sample from the subject;
- (B) calculating a systemic lupus erythematosus index score with the level of the erythrocyte C4d marker, the level of the B-cell C4d marker, the level of the anti-nuclear antibody, the level of anti-Sjögren's syndrome type B antigen antibody, the level of anti-Scl-70 antibody, the level of anti-Jo-1 antibody, and the level of anti-centromere protein B antibody with the equation:
- Index=−5.2626+0.9877×ANAComp[0.2955×log(EC4d)+1.0260×log(BC4d)]−2.4944×SpecComp;
- wherein:
- (i) Index is the systemic lupus erythematosus index score;
- (ii) ANAComp is:
- (a) 0, when the level of anti-nuclear antibody <20 units, as measured by an enzyme-linked immunosorbent assay;
- (b) 1, when the level of anti-nuclear antibody is ≥20 units and <60 units, as measured by an enzyme-linked immunosorbent assay;
- or
- (c) 2, when the level of anti-nuclear antibody ≥60 units, as measured by an enzyme-linked immunosorbent assay;
- (iii) log is natural log;
- (iv) EC4d is net mean fluorescence intensity of erythrocyte C4d marker, as measured by fluorescence activated flow cytometry;
- (v) BC4d is net mean fluorescence intensity of B-cell C4d marker, as measured by fluorescence activated flow cytometry;
- and
- (vi) SpecComp is:
- (a) 0, when the level of anti-Sjögren's syndrome type B antigen antibody is ≤10 Units/mL;
- the level of anti-Scl-70 antibody is ≤10 Units/mL;
- the level of anti-Jo-1 antibody is ≤10 Units/mL;
- and the level of anti-centromere protein B antibody is ≤10 Units/mL;
- where each are as measured by a fluoroenzymatic immunoassay;
- (b) 1, when one or more of the level of anti-Sjögren's syndrome type B antigen antibody is >10 Units/mL;
- the level of anti-Scl-70 antibody >10 Units/mL;
- the level of anti-Jo-1 antibody is >10 Units/mL;
- or the level of anti-centromere protein B antibody is >10 Units/mL;
- where each are as measured by a fluoroenzymatic immunoassay;
- (C) identifying the subject as having SLE when the index score is >0;
- and
- (D) treating the subject identified as having SLE in step (C) with an effective amount of azathioprine.
25 more elements
A method of treating systemic lupus erythematosus (SLE) in a subject identified as having SLE based on a systemic lupus erythematosus risk score, the method comprising:
- (A) determining a level of erythrocyte C4d marker, a level of B-cell C4d marker, a level of anti-nuclear antibody, a level of anti-Sjögren's syndrome type B antigen antibody, a level of anti-Scl-70 antibody, a level of anti-Jo-1 antibody, and a level of anti-centromere protein B antibody in a blood sample from the subject;
- (B) calculating a systemic lupus erythematosus index score with the level of the erythrocyte C4d marker, the level of the B-cell C4d marker, the level of the anti-nuclear antibody, the level of anti-Sjögren's syndrome type B antigen antibody, the level of anti-Scl-70 antibody, the level of anti-Jo-1 antibody, and the level of anti-centromere protein B antibody with the equation:
- Index=−5.2626+0.9877×ANAComp[0.2955×log(EC4d)+1.0260×log(BC4d)]−2.4944×SpecComp;
- wherein:
- (i) Index is the systemic lupus erythematosus index score;
- (ii) ANAComp is:
- (a) 0, when the level of anti-nuclear antibody <20 units, as measured by an enzyme-linked immunosorbent assay;
- (b) 1, when the level of anti-nuclear antibody is ≥20 units and <60 units, as measured by an enzyme-linked immunosorbent assay;
- or
- (c) 2, when the level of anti-nuclear antibody ≥60 units, as measured by an enzyme-linked immunosorbent assay;
- (iii) log is natural log;
- (iv) EC4d is net mean fluorescence intensity of erythrocyte C4d marker, as measured by fluorescence activated flow cytometry;
- (v) BC4d is net mean fluorescence intensity of B-cell C4d marker, as measured by fluorescence activated flow cytometry;
- and
- (vi) SpecComp is:
- (a) 0, when the level of anti-Sjögren's syndrome type B antigen antibody is ≤10 Units/mL;
- the level of anti-Scl-70 antibody is ≤10 Units/mL;
- the level of anti-Jo-1 antibody is ≤10 Units/mL;
- and the level of anti-centromere protein B antibody is ≤10 Units/mL;
- where each are as measured by a fluoroenzymatic immunoassay;
- (b) 1, when one or more of the level of anti-Sjögren's syndrome type B antigen antibody is >10 Units/mL;
- the level of anti-Scl-70 antibody >10 Units/mL;
- the level of anti-Jo-1 antibody is >10 Units/mL;
- or the level of anti-centromere protein B antibody is >10 Units/mL;
- where each are as measured by a fluoroenzymatic immunoassay;
- (C) identifying the subject as having SLE when the index score is >0;
- and
- (D) treating the subject identified as having SLE in step (C) with an effective amount of leflunomide.
25 more elements
A method of treating systemic lupus erythematosus (SLE) in a subject identified as having SLE based on a systemic lupus erythematosus risk score, the method comprising:
- (A) determining a level of erythrocyte C4d marker, a level of B-cell C4d marker, a level of anti-nuclear antibody, a level of anti-Sjögren's syndrome type B antigen antibody, a level of anti-Scl-70 antibody, a level of anti-Jo-1 antibody, and a level of anti-centromere protein B antibody in a blood sample from the subject;
- (B) calculating a systemic lupus erythematosus index score with the level of the erythrocyte C4d marker, the level of the B-cell C4d marker, the level of the anti-nuclear antibody, the level of anti-Sjögren's syndrome type B antigen antibody, the level of anti-Scl-70 antibody, the level of anti-Jo-1 antibody, and the level of anti-centromere protein B antibody with the equation:
- Index=−5.2626+0.9877×ANAComp[0.2955×log(EC4d)+1.0260×log(BC4d)]−2.4944×SpecComp;
- wherein:
- (i) Index is the systemic lupus erythematosus index score;
- (ii) ANAComp is:
- (a) 0, when the level of anti-nuclear antibody <20 units, as measured by an enzyme-linked immunosorbent assay;
- (b) 1, when the level of anti-nuclear antibody is ≥20 units and <60 units, as measured by an enzyme-linked immunosorbent assay;
- or
- (c) 2, when the level of anti-nuclear antibody ≥60 units, as measured by an enzyme-linked immunosorbent assay;
- (iii) log is natural log;
- (iv) EC4d is net mean fluorescence intensity of erythrocyte C4d marker, as measured by fluorescence activated flow cytometry;
- (v) BC4d is net mean fluorescence intensity of B-cell C4d marker, as measured by fluorescence activated flow cytometry;
- and
- (vi) SpecComp is:
- (a) 0, when the level of anti-Sjögren's syndrome type B antigen antibody is ≤10 Units/mL;
- the level of anti-Scl-70 antibody is ≤10 Units/mL;
- the level of anti-Jo-1 antibody is ≤10 Units/mL;
- and the level of anti-centromere protein B antibody is ≤10 Units/mL;
- where each are as measured by a fluoroenzymatic immunoassay;
- (b) 1, when one or more of the level of anti-Sjögren's syndrome type B antigen antibody is >10 Units/mL;
- the level of anti-Scl-70 antibody >10 Units/mL;
- the level of anti-Jo-1 antibody is >10 Units/mL;
- or the level of anti-centromere protein B antibody is >Units/mL;
- where each are as measured by a fluoroenzymatic immunoassay;
- (C) identifying the subject as having SLE when the index score is >0;
- and
- (D) treating the subject identified as having SLE in step (C) with an effective amount of hydroxychloroquine.
25 more elements
A method of treating systemic lupus erythematosus (SLE) in a subject identified as having SLE, the method comprising:
- (A) determining a level of erythrocyte C4d marker, a level of B-cell C4d marker, a level of anti-nuclear antibody, a level of Sjögren's syndrome type B antigen, a level of Scl-70 antibody, a level of Jo-1 antibody, and a level of centromere B protein in a blood sample from the subject;
- (B) calculating a systemic lupus erythematosus index score with the levels of erythrocyte C4d marker, B-cell C4d marker, anti-nuclear antibody, Sjögren's syndrome type B antigen, Scl-70 antibody, Jo-1 antibody, and centromere B protein with the equation:
- Index=−5.2626+0.9877×ANAComp[0.2955×log(EC4d)+1.0260×log(BC4d)]−2.4944×SpecComp;
- wherein:
- (i) Index is the systemic lupus erythematosus index score;
- (ii) ANAComp is:
- (a) 0, when the level of anti-nuclear antibody <20 units, as measured by an enzyme-linkedimmunosorbent assay;
- (b) 1, when the level of anti-nuclear antibody is ≥20 units and <60 units, as measured by an enzyme-linked immunosorbent assay;
- or
- (c) 2, when the level of anti-nuclear antibody ≥60 units, as measured by an enzyme-linkedimmunosorbent assay;
- (iii) log is natural log;
- (iv) EC4d is net mean fluorescence intensity of erythrocyte C4d marker, as measured by fluorescence activated flow cytometry;
- (v) BC4d is net mean fluorescence intensity of B-cell C4d marker, as measured by fluorescence activated flow cytometry;
- and
- (vi) SpecComp is:
- (a) 0, when the level of Sjögren's syndrome type B antigen is ≤10 Units/mL;
- the level of Scl-70 antibody is ≤10 Units/mL;
- the level of Jo-1 antibody is ≤10 Units/mL;
- and the level of centromere B protein is ≤10 Units/mL;
- where each are as measured by a fluoroenzymatic immunoassay;
- (b) 1, when one or more of the level of Sjögren's syndrome type B antigen is >10 Units/mL;
- the level of Scl-70 antibody >10 Units/mL;
- the level of Jo-1 antibody is >10 Units/mL;
- or the level of centromere B protein is >10 Units/mL;
- where each are as measured by a fluoroenzymatic immunoassay;
- (C) identifying the subject as having SLE when the index score is >0;
- and
- (D) treating the subject identified as having SLE in step (C) with an effective amount of a corticosteroid.
25 more elements
Dependencies are inferred from the claim text.