title: SPRi-based strategy to identify specific biomarkers in systemic lupus erythematosus, rheumatoid arthritis and autoimmune hepatitis.
abstract: BACKGROUND
  Heterogeneous nuclear ribonucleoprotein (hnRNP) A2/B1 is a target for antinuclear autoantibodies in systemic Lupus erythematosus (SLE), rheumatoid arthritis (RA), and autoimmune hepatitis (AIH).
  
  
  OBJECTIVE
  To monitor molecular interactions between peptides spanning the entire sequence of hnRNP A2/B1 and sera from patients and healthy controls.
  
  
  METHODS
  Sera from 8 patients from each pathology and controls were passed across a surface plasmon resonance Imagery (SPRi) surface containing 39 overlapping peptides of 17 mers covering the human hnRNP B1. Interactions involving the immobilised peptides were followed in real time and dissociation rate constants k(off) for each interaction were calculated.
  
  
  RESULTS
  Several significant interactions were observed: i) high stability (lower k(off) values) between P₅₅₋₇₀ and the AIH sera compared to controls (p= 0.003); ii) lower stability (higher k(off) values) between P₁₁₈₋₁₃₃ and P₂₆₂₋₂₇₇ and SLE sera, P₁₄₅₋₁₆₀ and RA sera compared to controls (p=0.006, p=0.002, p=0.007). The binding curves and k(off) values observed after the formation of complexes with anti-IgM and anti-IgG antibodies and after nuclease treatment of the serum indicate that i) IgM isotypes are prevalent and ii) nucleic acids participate in the interaction between anti-hnRNAP B1 and P₅₅₋₇₀ and also between controls and the peptides studied.
  
  
  CONCLUSIONS
  These results indicate that P₅₅₋₇₀ of hnRNP B1 is a potential biomarker for AIH in immunological tests and suggest the role of circulating nucleic acids, (eg miRNA), present or absent according to the autoimmune disorders and involved in antigen-antibody stability.
authors.affiliation: Research Unit 785, Inserm, Villejuif, France ; Faculte de Medecine, University Paris-Sud, Villejuif, France.
authors.forename: Elvire
authors.initials: E
authors.lastname: Beleoken
authors.affiliation: Laboratoire de Biologie et de Pharmacologie Appliquée, ENS Cachan - CNRS, Cachan, France.
authors.forename: Hervé
authors.initials: H
authors.lastname: Leh
authors.affiliation: Unité de Recherche Clinique, AP-HP Hopital Bicetre, Le Kremlin-Bicetre, France.
authors.forename: Armelle
authors.initials: A
authors.lastname: Arnoux
authors.affiliation: Faculte de Medecine, University Paris-Sud, Villejuif, France ; Unit 1018 - Centre for research in Epidemiology and Population Health, INSERM, Le Kremlin-Bicetre, France.
authors.forename: Béatrice
authors.initials: B
authors.lastname: Ducot
authors.affiliation: Laboratoire de Biologie et de Pharmacologie Appliquée, ENS Cachan - CNRS, Cachan, France.
authors.forename: Claude
authors.initials: C
authors.lastname: Nogues
authors.affiliation: Research Unit 785, Inserm, Villejuif, France ; Faculte de Medecine, University Paris-Sud, Villejuif, France ; Laboratoire Immunologie, AP-HP Hopital Saint-Antoine, Paris, France.
authors.forename: Eleonora
authors.initials: E
authors.lastname: De Martin
authors.affiliation: Research Unit 785, Inserm, Villejuif, France ; Laboratoire Immunologie, AP-HP Hopital Saint-Antoine, Paris, France ; Faculté de Médecine UFR 967, Université Pierre et Marie Curie, Paris, France.
authors.forename: Catherine
authors.initials: C
authors.lastname: Johanet
authors.affiliation: Research Unit 785, Inserm, Villejuif, France ; Faculte de Medecine, University Paris-Sud, Villejuif, France ; Centre Hépato-Biliaire, AP-HP Hôpital Paul Brousse, Villejuif, France.
authors.forename: Didier
authors.initials: D
authors.lastname: Samuel
authors.affiliation: Research Unit 785, Inserm, Villejuif, France ; Faculte de Medecine, University Paris-Sud, Villejuif, France.
authors.forename: Mohammad Zahid
authors.initials: MZ
authors.lastname: Mustafa
authors.affiliation: Research Unit 785, Inserm, Villejuif, France ; Faculte de Medecine, University Paris-Sud, Villejuif, France ; Centre Hépato-Biliaire, AP-HP Hôpital Paul Brousse, Villejuif, France.
authors.forename: Jean-Charles
authors.initials: JC
authors.lastname: Duclos-Vallée
authors.affiliation: Laboratoire de Biologie et de Pharmacologie Appliquée, ENS Cachan - CNRS, Cachan, France.
authors.forename: Malcolm
authors.initials: M
authors.lastname: Buckle
authors.affiliation: Research Unit 785, Inserm, Villejuif, France ; Faculte de Medecine, University Paris-Sud, Villejuif, France ; Laboratoire Immunologie, AP-HP Hopital Saint-Antoine, Paris, France.
authors.forename: Eric
authors.initials: E
authors.lastname: Ballot
mesh_terms: D000974:Antibodies, Antinuclear / Q000378:metabolism; D001172:Arthritis, Rheumatoid / Q000378:metabolism*; D015415:Biomarkers / Q000378:metabolism*; D004591:Electrophoresis, Polyacrylamide Gel; D019084:Fluorescent Antibody Technique, Indirect; D019693:Hepatitis, Autoimmune / Q000378:metabolism*; D034481:Heterogeneous-Nuclear Ribonucleoprotein Group A-B / Q000378:metabolism*; D006801:Humans; D015151:Immunoblotting; D008180:Lupus Erythematosus, Systemic / Q000378:metabolism*; D010455:Peptides / Q000378:metabolism; D018709:Statistics, Nonparametric; D020349:Surface Plasmon Resonance / Q000379:methods*
chemical_list: D000974:Antibodies, Antinuclear; D015415:Biomarkers; D034481:Heterogeneous-Nuclear Ribonucleoprotein Group A-B; D010455:Peptides