Biomarkers, Methods and Kits for the Diagnosis of Rheumatoid Arthritis
AssigneeUniversite De La Mediterranee - Aix-Marseille 11
InventorsIsabelle Auger, Jean Roudier
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Abstract
The present invention relates to peptides biomarkers that are specifically recognized by autoantibodies present in the sera of patients with Rheumatoid Arthritis (RA). More specifically, the invention provides epitopes of PAD4, of BRAF, and of calpastatin as well as methods and kits for using these sequences for the diagnosis of RA, in particular for the diagnosis of RA in CCP-negative subjects.
Claims17
A method for diagnosing rheumatoid arthritis in a subject, said method comprising steps of:
- contacting a biological sample obtained from the subject with at least one biomarker for a time and under conditions allowing a biomarker-antibody complex to form, wherein the at least one biomarker is selected from the group consisting of:
- PAD4-peptides having an amino acid sequence comprising or consisting of a sequence selected from the group consisting of SEQ ID NO:
- 2, SEQ ID NO:
- 3, SEQ ID NO:
- 4, analogues thereof, and fragments thereof,
- BRAF-peptides having an amino acid sequence comprising or consisting of a sequence selected from the group consisting of SEQ ID NO:
- 7, SEQ ID NO:
- 8, SEQ ID NO:
- 9, analogues thereof, and fragments thereof, and
- any combination thereof;
- and
- detecting any biomarker-antibody complex formed,
- wherein detection of a biomarker-antibody complex is indicative of rheumatoid arthritis in the subject.
A method for detecting the presence of anti-PAD4 autoantibodies or anti-BRAF autoantibodies in a biological sample, said method comprising steps of:
- contacting the biological sample with at least one biomarker for a time and under conditions allowing a biomarker-antibody complex to form,
- wherein the at least one biomarker is a PAD4 peptide having an amino acid sequence comprising or consisting of a sequence selected from the group consisting of SEQ ID NO:
- 2, SEQ ID NO:
- 3, SEQ ID NO:
- 4, SEQ ID NO:
- 5, analogues thereof, fragments thereof, and any combination thereof, or
- wherein the at least one biomarker is a BRAF-peptide having an amino acid sequence comprising or consisting of a sequence selected from the group consisting of SEQ ID NO:
- 7, SEQ ID NO:
- 8, SEQ ID NO:
- 9, analogues thereof, fragments thereof, and any combination thereof;
- and
- detecting any biomarker-antibody complex formed,
- wherein detection of a PAD4 peptide-antibody complex is indicative of the presence of anti-PAD4 autoantibodies in the biological sample, and wherein detection of a BRAF peptide-antibody complex is indicative of the presence of anti-BRAF autoantibodies in the biological sample.
5-8. (canceled)
A kit for the in vitro diagnosis of rheumatoid arthritis in a subject, said kit comprising:
- at least two biomarkers selected from the group consisting of:
- PAD4-peptides having an amino acid sequence comprising or consisting of a sequence selected from the group consisting of SEQ ID NO:
- 2, SEQ ID NO:
- 3, SEQ ID NO:
- 4, analogues thereof, and fragments thereof,
- BRAF-peptides having an amino acid sequence comprising or consisting of a sequence selected from the group consisting of SEQ ID NO:
- 7, SEQ ID NO:
- 8, SEQ ID NO:
- 9, analogues thereof, and fragments thereof,
- calpastatin-peptides having an amino acid sequence comprising or consisting of a sequence selected from the group consisting of SEQ ID NO:
- 11, SEQ ID NO:
- 12, analogues thereof, and fragments thereof, and
- any combination thereof;
- and
- at least one reagent for detecting a biomarker-antibody complex formed between the biomarker and an autoantibody present in a biological sample obtained from the subject, wherein detection of a biomarker-antibody complex is indicative of rheumatoid arthritis in the subject.
A kit for detecting the presence of anti-PAD4 autoantibodies or anti-BRAF autoantibodies in a biological sample, said kit comprising:
- at least one biomarker,
- wherein the at least one biomarker is a PAD4-peptide having an amino acid sequence comprising or consisting of a sequence selected from the group consisting of SEQ ID NO:
- 2, SEQ ID NO:
- 3, SEQ ID NO:
- 4, SEQ ID NO:
- 5, analogues thereof, fragments thereof, and any combination thereof, or
- wherein the at least one biomarker is a BRAF-peptide having an amino acid sequence comprising or consisting of a sequence selected from the group consisting of SEQ ID NO:
- 7, SEQ ID NO:
- 8, SEQ ID NO:
- 9, analogues thereof, fragments thereof, and any combination thereof;
- and
- at least one reagent for detecting a biomarker-antibody complex formed between the biomarker and an autoantibody present in the biological sample, wherein the autoantibody is an anti-PAD4 autoantibody or an anti-BRAF autoantibody that is indicative of rheumatoid arthritis.
12-13. (canceled)
An array for diagnosing rheumatoid arthritis in a subject, said array comprising, attached to its surface at least two biomarkers, wherein the at least two biomarkers are selected from the group consisting of:
- PAD4-peptides having an amino acid sequence comprising or consisting of a sequence selected from the group consisting of SEQ ID NO:
- 2, SEQ ID NO:
- 3, SEQ ID NO:
- 4, analogues thereof, and fragments thereof,
- BRAF-peptides having an amino acid sequence comprising or consisting of a sequence selected from the group consisting of SEQ ID NO:
- 7, SEQ ID NO:
- 8, SEQ ID NO:
- 9, analogues thereof, and fragments thereof,
- calpastatin-peptides having an amino acid sequence comprising or consisting of a sequence selected from the group consisting of SEQ ID NO:
- 11, SEQ ID NO:
- 12, analogues thereof, and fragments thereof, and
- any combination thereof.
(canceled)
A biomarker of rheumatoid arthritis, wherein the biomarker is:
- a PAD4-peptide having an amino acid sequence comprising or consisting of a sequence selected from the group consisting of SEQ ID NO:
- 2, SEQ ID NO:
- 3, SEQ ID NO:
- 4, SEQ ID NO:
- 5, analogues thereof, and fragments thereof, and wherein the biomarker is recognized by an anti-PAD4 autoantibody, or
- a BRAF-peptide having an amino acid sequence comprising or consisting of a sequence selected from the group consisting of SEQ ID NO:
- 7, SEQ ID NO:
- 8, SEQ ID NO:
- 9, analogues thereof, and fragments thereof, and wherein the biomarker is recognized by an anti-BRAF autoantibody, or
- a calpastatin-peptide having an amino acid sequence comprising or consisting of a sequence selected from the group consisting of SEQ ID NO:
- 11, SEQ ID NO:
- 12, analogues thereof, and fragments thereof, and wherein the biomarker is recognized by an
19-21. (canceled)
Dependencies are inferred from the claim text.