Identification and characterization of a peptide mimetic that may detect a species of disease-associated anticardiolipin antibodies in patients with the antiphospholipid syndrome.

Abstract

OBJECTIVE:

To test the feasibility of applying a mimetic (specific for a patient-derived prothrombotic anticardiolipin antibody [aCL]) to study the homologous, disease-associated aCL in patients with antiphospholipid syndrome (APS).

METHODS:

We used the CL15 monoclonal aCL to screen 17 phage-display peptide libraries. Peptides (corresponding to recurrent peptide sequences) and their derivatives were synthesized and analyzed for binding to CL15 and for their abilities to inhibit CL15 from binding to cardiolipin. A peptide was chosen and used to study CL15-like IgG aCL in plasma samples from patients with APS, patients with systemic lupus erythematosus (SLE) but without APS, and normal healthy donors.

RESULTS:

Library screening with CL15 yielded 4 recurrent peptide sequences. Analyses of peptides showed that peptide CL154C reacted with antibody CL15 and inhibited binding of CL15 to cardiolipin, indicating that peptide CL154C may be a peptide mimetic for the CL15 aCL. Initial studies with plasma samples revealed that CL154C-reactive IgG was present (positivity defined as the mean + 3 SD optical density of the 25 normal controls) in 15 of 21 APS patients and 1 of 12 SLE patients.

CONCLUSION:

These findings suggest that it is feasible to develop a specific enzyme-linked immunosorbent assay for each immunologically and functionally distinct disease-associated aCL. Additional testing of CL154C with a larger number of APS patients and SLE patients, as well as identification of peptide mimetics for each distinct aCL, will reveal the diagnostic potential of CL154C and other mimetics in identifying patients with aCL who are at risk of developing life-threatening thrombosis.

• Authors: Sudha Visvanathan, Jamie K Scott, Kwan-Ki Hwang, Michelle Banares, Jennifer M Grossman, Joan T Merrill, John FitzGerald, Reginald U Chukwuocha, Betty P Tsao, Bevra H Hahn, Pojen P Chen
• Journal: Arthritis and rheumatism (Arthritis Rheum) Vol. 48 Issue 3 Pg. 737-45 (Mar 2003) ISSN: 0004-3591 [Print] United States
• PMID: 12632428 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Antibodies, Anticardiolipin
• Antibodies, Monoclonal
• Oligopeptides
• Peptide Fragments
• Peptide Library

Topics

• Adolescent
• Adult
• Aged
• Antibodies, Anticardiolipin (blood, immunology)
• Antibodies, Monoclonal (chemistry, immunology)
• Antibody Specificity
• Antiphospholipid Syndrome (blood, diagnosis, immunology)
• Child
• Enzyme-Linked Immunosorbent Assay
• Female
• Humans
• Male
• Middle Aged
• Molecular Mimicry
• Oligopeptides (chemical synthesis, immunology)
• Peptide Biosynthesis
• Peptide Fragments (chemical synthesis, immunology)
• Peptide Library