title: Felty's syndrome and hypofibrinogenemia: an unusual target for anti-cyclic citrullinated peptide antibodies?
abstract: BACKGROUND
  Rheumatoid arthritis (RA) is a risk factor for the development of Felty's syndrome and large granular lymphocyte (LGL) leukemia. Anti-cyclic citrullinated peptide (CCP) antibodies are considered highly specific for RA and are directed against various citrullinated antigens, including citrullinated fibrinogen. Anti-CCP antibodies may interfere with the detection of citrullinated proteins and their function. In this article, we describe the possible inhibition of fibrinogen by anti-CCP antibodies with clinical consequences which have never been reported in the literature to our best knowledge.
  
  
  METHODS
  We present the case of a 79-year-old Caucasian woman with a longstanding history of untreated seropositive RA and who had been investigated for severe neutropenia since several months. The association of splenomegaly led to suspicion of Felty's syndrome. Flux cytometry was compatible with T-cell LGL leukemia. In addition, severe hypofibrinogenemia was detected. The later finding has not been consistently associated with the former clinical entities. Further investigations demonstrated that the anti-CCP antibodies of the patient also recognized the P41 peptide of citrullinated fibrinogen. The patient deceased of intracranial hemorrhage.
  
  
  CONCLUSIONS
  It is likely, yet not definite, that high anti-citrullinated fibrinogen titers may contribute to low fibrinogen levels and could have contributed to the fatal hemorrhagic event.
authors.affiliation: a Division of Immunology and Allergology, University Hospitals of Geneva , Switzerland.
authors.forename: Ilias
authors.initials: I
authors.lastname: Lazarou
authors.forename: Nicolas
authors.initials: N
authors.lastname: Petitpierre
authors.forename: Isabelle
authors.initials: I
authors.lastname: Auger
authors.forename: Guido
authors.initials: G
authors.lastname: Reber
authors.forename: Pascale
authors.initials: P
authors.lastname: Roux-Lombard
authors.forename: Françoise
authors.initials: F
authors.lastname: Boehlen
authors.forename: Jean
authors.initials: J
authors.lastname: Villard
mesh_terms: D000368:Aged; D001323:Autoantibodies / Q000097:blood / Q000276:immunology*; D005258:Felty Syndrome / Q000097:blood / Q000276:immunology*; D005260:Female; D005340:Fibrinogen / Q000378:metabolism*; D006801:Humans; D010456:Peptides, Cyclic / Q000097:blood / Q000276:immunology*
chemical_list: D001323:Autoantibodies; D010456:Peptides, Cyclic; C487763:cyclic citrullinated peptide; D005340:Fibrinogen
keywords: Anti-cyclic citrullinated peptide antibodies; Felty's; Fibrinogen; Rheumatoid arthritis