Synthesis of overlapping fibrin citrullinated peptides and their use for diagnosing rheumatoid arthritis.
With the aim of developing a new enzyme-linked immunosorbent assay test to detect autoantibodies in the sera of rheumatoid arthritis patients with a high sensitivity and specificity using synthetic citrullinated peptides of fibrin (which is abundant in rheumatoid synovium) as antigenic substract, peptides belonging to alpha- and beta-fibrin chains were selected by computer-aided prediction of antigenicity and epitope mapping and synthesized in solid phase. We analysed by enzyme-linked immunosorbent assay 133 sera from patients with well-characterized rheumatic diseases, including 67 patients with rheumatoid arthritis. The results of the immunoassays reported highlight the usefulness of fibrin-related peptides in rheumatoid arthritis diagnosis and, especially, the ability and specificity of the [Cit(621,627,630)]alpha-fibrin(617-631) (alpha fib617) peptide sequence to recognize the autoantibodies that are present in rheumatoid arthritis patients.
Pérez
María L
ML
Department of Peptide & Protein Chemistry, IIQAB-CSIC Jordi Girona, 18-26 08034 Barcelona, Spain.
Gómara
María J
MJ
Kasi
Devi
D
Alonso
Ana
A
Viñas
Odette
O
Ercilla
Guadalupe
G
Sanmartí
Raimon
R
Haro
Isabel
I
D000595:Amino Acid Sequence; D001172:Arthritis, Rheumatoid / Q000097:blood / Q000175:diagnosis* / Q000276:immunology; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D002956:Citrulline / Q000031:analogs & derivatives* / Q000737:chemistry; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D018604:Epitope Mapping / Q000379:methods; D005337:Fibrin / Q000138:chemical synthesis* / Q000737:chemistry / Q000276:immunology; D000091344:Filaggrin Proteins; D006801:Humans; D016056:Immunodominant Epitopes / Q000276:immunology; D007381:Intermediate Filament Proteins / Q000737:chemistry / Q000276:immunology; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000138:chemical synthesis* / Q000737:chemistry / Q000276:immunology; D010456:Peptides, Cyclic / Q000138:chemical synthesis* / Q000737:chemistry / Q000276:immunology; D012680:Sensitivity and Specificity; D020539:Sequence Analysis, Protein / Q000379:methods
D000091344:Filaggrin Proteins; D016056:Immunodominant Epitopes; D007381:Intermediate Filament Proteins; D010446:Peptide Fragments; D010456:Peptides, Cyclic; C487763:cyclic citrullinated peptide; D002956:Citrulline; D005337:Fibrin