Method of detecting auto-antibodies from patients suffering from rheumatoid arthritis, a peptide and assay kit
AssigneeStichting voor de Technische Wetenschappen
InventorsWaltherus Jacobus Wilhelmus VAN VENROOIJ, Jan Wouter DRIJFHOUT, Martinus Adrianus Maria VAN BOEKEL, Gerardus Jozef Maria PRUIJN
Life of this patent
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Abstract
Peptides useful in determining the presence of autoantibodies in patients suffering from rheumatoid arthritis are disclosed.
Claims25
A method to detect the presence or absence of autoantibodies associated with rheumatoid arthritis (RA), which method comprises contacting a sample suspected of containing said antibodies with at least two peptide units for a time sufficiently long to allow a complex to be formed between the at least one of said peptide units and any said autoantibodies, and
- detecting the presence or absence of the complex peptide unit wherein at least one peptide unit comprises the motif XG, and at least one peptide unit comprises the motif XnonG, wherein X is a citrulline residue or an analog thereof, G is the amino acid glycine and nonG is an amino acid other than glycine.
A peptide comprising a sequence with the formula (II):
- (A1-A2-A3-A4-A5)-Cit-(A6)-(A7-A8-A9-A10-A11) (II)
- wherein
- A1-A2-A3-A4-A5 is an amino acid sequence selected from the group consisting of:
- (SEQ ID NO:
- 13)
- RHGRQ
- (SEQ ID NO:
- 14)
- IRCitYK
- (SEQ ID NO:
- 15)
- HGRQCit
- (SEQ ID NO:
- 16)
- GRQCitCit
- (SEQ ID NO:
- 17)
- FQMCitH
- (SEQ ID NO:
- 18)
- CitWRGM
- (SEQ ID NO:
- 19)
- ARFQM
- (SEQ ID NO:
- 20)
- QCitYKW
- (SEQ ID NO:
- 21)
- KPYTV
- (SEQ ID NO:
- 22)
- NRLRL
- (SEQ ID NO:
- 23)
- RRRCitY
- (SEQ ID NO:
- 24)
- RFKSN
- (SEQ ID NO:
- 25)
- RGKSN
- (SEQ ID NO:
- 26)
- RWVSQ
- (SEQ ID NO:
- 27)
- MKPRY
- (SEQ ID NO:
- 28)
- KSFVW
- (SEQ ID NO:
- 29)
- YSFVW
- (SEQ ID NO:
- 30)
- FQMRH
- (SEQ ID NO:
- 31)
- RNMNR
- and
- (SEQ ID NO:
- 32)
- RMGRP
- and sequences homologous thereto;
- A6 represents an amino acid other than glycine;
- A7-A8-A9-A10-A11 represents an amino acid sequence selected from the group consisting of:
- (SEQ ID NO:
- 33)
- KYIIY
- (SEQ ID NO:
- 34)
- TNRKF
- (SEQ ID NO:
- 35)
- KWCitKI
- (SEQ ID NO:
- 36)
- CitRAVI
- (SEQ ID NO:
- 37)
- RCitGHS
- (SEQ ID NO:
- 38)
- CitGRSR
- (SEQ ID NO:
- 39)
- CitYIIY
- (SEQ ID NO:
- 40)
- CitRLIR
- (SEQ ID NO:
- 41)
- IERKR
- (SEQ ID NO:
- 42)
- FMRKP
- (SEQ ID NO:
- 43)
- FMRRP
- (SEQ ID NO:
- 44)
- ERNHA
- (SEQ ID NO:
- 45)
- AVITA
- (SEQ ID NO:
- 46)
- TPNRW
- (SEQ ID NO:
- 47)
- TYNRW
- (SEQ ID NO:
- 48)
- RTPTR
- (SEQ ID NO:
- 49)
- RIVVV
- (SEQ ID NO:
- 50)
- HARPR
- (SEQ ID NO:
- 51)
- RGMCitR
- and
- (SEQ ID NO:
- 52)
- IRFPV
- and sequences homologous thereto.
A peptide comprising a sequence with the formula (III):
- (B1-B2-B3-B4-B5-B6)-Cit-(B7)-(B8-B9-B10-B11) (III)
- wherein
- B1-B2-B3-B4-B5-B6 is an amino acid sequence selected from the group consisting of:
- (SEQ ID NO:
- 53)
- INCitRAS
- (SEQ ID NO:
- 54)
- ICitKRLY
- (SEQ ID NO:
- 55)
- KCitCitYNI
- (SEQ ID NO:
- 56)
- RLYFICit
- (SEQ ID NO:
- 57)
- IRQGAR
- (SEQ ID NO:
- 58)
- CitERCitVQ
- (SEQ ID NO:
- 59)
- CitHQRIT
- (SEQ ID NO:
- 60)
- RICitRVCit
- (SEQ ID NO:
- 61)
- GRNQRY
- (SEQ ID NO:
- 62)
- RCitRQHP
- (SEQ ID NO:
- 63)
- CitCitRCitVA
- (SEQ ID NO:
- 64)
- RPKQHV
- (SEQ ID NO:
- 65)
- RKCitGCitR
- (SEQ ID NO:
- 66)
- RCitCitRNT
- (SEQ ID NO:
- 67)
- RCitQCitFT
- (SEQ ID NO:
- 68)
- QLVYLQ
- (SEQ ID NO:
- 69)
- QYNRFK
- (SEQ ID NO:
- 70)
- CitLRHIR
- (SEQ ID NO:
- 71)
- PRCitCitCitK
- (SEQ ID NO:
- 72)
- RCitQVRY
- (SEQ ID NO:
- 73)
- GRCitHAH
- (SEQ ID NO:
- 74)
- ARHVIR
- (SEQ ID NO:
- 75)
- RCitGHMF
- (SEQ ID NO:
- 76)
- GRNIRV
- (SEQ ID NO:
- 77)
- QIFYLCit
- (SEQ ID NO:
- 78)
- RQGPIA
- (SEQ ID NO:
- 79)
- GVYLVR
- (SEQ ID NO:
- 80)
- NCitCitRRV
- (SEQ ID NO:
- 81)
- KCitRLCitY
- (SEQ ID NO:
- 82)
- GRRCitCitL
- and
- (SEQ ID NO:
- 83
- RMPHCitH
- and sequences homologous thereto;
- B7 represents an amino acid other than glycine;
- B8-B9-B10-B11 represents an amino acid sequence selected from the group consisting of:
- (SEQ ID NO:
- 84)
- CitHRR
- (SEQ ID NO:
- 85)
- CitIRR
- (SEQ ID NO:
- 86)
- FRRN
- (SEQ ID NO:
- 87)
- AQTT
- (SEQ ID NO:
- 88)
- GYPK
- (SEQ ID NO:
- 89)
- RPPQ
- (SEQ ID NO:
- 90)
- GCitRK
- (SEQ ID NO:
- 91)
- PIPR
- (SEQ ID NO:
- 92)
- YTIH
- (SEQ ID NO:
- 93)
- RIKA
- (SEQ ID NO:
- 94)
- CitRVR
- (SEQ ID NO:
- 95)
- TRRP
- (SEQ ID NO:
- 96)
- TIRP
- (SEQ ID NO:
- 97)
- IKCitR
- (SEQ ID NO:
- 98)
- RNVV
- (SEQ ID NO:
- 99)
- CitRRy
- (SEQ ID NO:
- 100)
- CitRPR
- (SEQ ID NO:
- 101)
- TRCitCit
- (SEQ ID NO:
- 102)
- CitCitGR
- (SEQ ID NO:
- 103)
- LCitRCit
- (SEQ ID NO:
- 104)
- RVRCit
- (SEQ ID NO:
- 105)
- VPRT
- (SEQ ID NO:
- 106)
- YCitFR
- (SEQ ID NO:
- 107)
- ARCitCit
- (SEQ ID NO:
- 108)
- RQCitR
- (SEQ ID NO:
- 109)
- HIRR
- (SEQ ID NO:
- 110)
- CitMMR
- (SEQ ID NO:
- 111)
- CitRICit
- (SEQ ID NO:
- 112)
- VRKS
- (SEQ ID NO:
- 113)
- PCitCitR
- and
- (SEQ ID NO:
- 114)
- CitRRK
- and sequences homologous thereto.
A peptide comprising a sequence with the formula (IV)
- (C1-C2)-(C3-C4-C5)-X-G-C6-(C7-C8-C9-C10) (IV)
- wherein
- C1-C2 is HQ, GF, EG or GV;
- C3-C4-05 represents 3 amino acids of which at least 1 is basic, aromatic or V;
- C6 is a basic or aromatic amino acid, or is A, G, E, P, V, S or Cit or analog thereof;
- and
- C7-C8-C9-C10 is SRAA (SEQ ID NO:208), SCitAA (SEQ ID NO:209), RPLD (SEQ ID NO:210), RVVE (SEQ ID NO:211) or PGLD (SEQ ID NO:212);
- and analogs of the peptide with the formula (IV).
A peptide comprising
- (a) a peptide unit with the formula (II) or (III) or analogs thereof and
- (b) a peptide with the formula (IV) or an analog thereof
- wherein each peptide unit may be linear or cyclic.
A method to select a peptide for diagnosis of RA, which comprises screening a peptide library with antibodies obtained from patients with RA and wherein the peptide library is selected from a group consisting of:
- Lib (1):
- (SEQ ID NO:
- 202)
- H Q E X X Cit X X S R A A
- Wherein X=any amino acid except cysteine and tryptophan;
- Lib (2):
- (SEQ ID NOS:
- 203-204)
- H Q X X X Cit G X S R/Cit A A
- Wherein X=any amino acid except cysteine but including Citrulline;
- Lib (3):
- (SEQ ID NOS:
- 205-206)
- H Q E X X Cit X X S R/Cit A A
- Wherein X=any amino acid except cysteine but including Citrulline;
- and
- Lib (4):
- (SEQ ID NO:
- 207)
- X X X X X X Cit X X X X X
- Wherein X=any amino acid except cysteine but including Citrulline or equivalents thereof.
Dependencies are inferred from the claim text.