T-CELL RECEPTOR CLONOTYPES SHARED AMONG ANKYLOSING SPONDYLITIS PATIENTS
The invention includes a method for determining the disease status of an individual suffering from ankylosing spondylitis by monitoring the individual's T-cell repertoire for the presence and/or level of clonotypes encoding T-cell receptor chains with segments identical to ant or related to the peptide LCASSLEASGSSYNEQFFGPGTRLTV (SEQ ID NO: 1) or the peptide VYFCASSDSSGSTDTQYFGPGTRLTV (SEQ ID NO: 2). The invention also includes therapeutic antibodies specific for these peptides for ameliorating the effects ankylosing spondylitis.
1 - 11 . (canceled)
12 . A method for treating ankylosing spondylitis in a subject in need thereof, the method comprising administering an effective amount of a medication selected from the group consisting of an antibody specific for a T cell receptor, an anti-inflammatory drug, a disease modifying anti-rheumatic drug (DMARD), and a TNFα blocker to a subject in need thereof identified as having an elevated level of T cells expressing T-cell receptors comprising LCASSLEASGSSYNEQFFGPGTRLTV (SEQ ID NO: 1) and/or VYFCASSDSSGSTDTQYFGPGTRLTV (SEQ ID NO: 2).
13 . The method of claim 12 , wherein the elevated level is identified by generating a clonotype profile of a tissue sample obtained from the subject.
14 . The method of claim 13 , wherein the tissue sample is a blood sample.
15 . The method of claim 13 , wherein generating a clonotype profile comprises:
amplifying nucleic acid molecules comprising recombined DNA sequences from T-cell receptor genes obtained from T-cells of the tissue sample;
sequencing the amplified nucleic acid molecules to form a clonotype profile; and
determining the levels of clonotypes in the clonotype profile.
16 . The method of claim 13 , wherein the elevated level of the clonotype is at least 0.000001 percent of clonotypes in the clonotype profile.
17 . The method of claim 13 , wherein the elevated level of the clonotype is at least 0.0001 percent of clonotypes in the clonotype profile.
18 . The method of claim 13 , wherein the elevated level of the clonotype is at least 0.001 percent of clonotypes in the clonotype profile.
19 . The method of claim 12 , wherein the elevated level is statistically significantly different from a level determined from a control sample of a healthy individual.
20 . The method of claim 12 , wherein the antibody specific to a T-cell receptor is directed against an amino acid segment selected from the groups consisting of LCASSLEASGSSYNEQFFGPGTRLTV (SEQ ID NO: 1) and any 6 to 20 amino acid segment thereof or VYFCASSDSSGSTDTQYFGPGTRLTV (SEQ ID NO: 2) and any 6 to 20 amino acid segment thereof.