title: Ferritin in the antiphospholipid syndrome and its catastrophic variant (cAPS).
abstract: BACKGROUND
  Ferritin is an iron storage protein considered also as an acute phase reactant with high levels in various inflammatory conditions. Recently, a plausible role for ferritin in the pathogenesis of immune-mediated and especially autoimmune diseases has been suggested. However, the link between ferritin and the antiphospholipid syndrome (APS) has been rarely explored. Therefore, in the current study we evaluated ferritin levels and their correlation to clinical and serological manifestations in patients with APS. We further analyzed ferritin levels among patients with the catastrophic variant of APS (cAPS).
  
  
  METHODS
  Ferritin levels were determined in serum samples of 176 APS patients and 98 matched healthy controls according to age and sex (LIAISON, DiaSorin, Italy). APS samples were further analyzed for antiphospholipid (anti-cardiolipin, anti- beta-2-glycoprotein, lupus anticoagulant) and anti-infectious antibodies (CMV, EBV, rubella, toxoplasma, HBV) (LIAISON, DiaSorin, Italy). Clinical, serological and demographic manifestations were recorded. An additional analysis of ferritin levels among 14 patients with cAPS was performed.
  
  
  RESULTS
  Hyperferritinemia was present in 9% vs. 0% of APS patients and controls, respectively (p < 0.001). Among patients with APS, ferritin levels correlated with venous thrombosis, cardiac, neurological, and hematological manifestations and the presence of anti-CMV-IgM antibodies. Hyperferritinemia was present in 71% of cAPS patients, and ferritin levels among this subgroup were significantly higher compared with APS-non-cAPS patients (816 ± 847 ng/ml vs. 120 ± 230 ng/ml, p < 0.001).
  
  
  CONCLUSIONS
  Herein, we found that hyperferritinemia correlates with the presence of APS, its clinical manifestations and specifically with the catastrophic variant of this disease. Hyperferritinemia was also linked with anti-CMV antibodies among patients with APS. These associations allude to a pathogenic role of ferritin in the pathogenesis of APS, and the plausible role of ferritin as a marker of ensuing cAPS, although further studies are needed to elucidate these associations.
authors.affiliation: 1The Zabludowicz Center for Autoimmune Diseases, Sheba Medical Center, Tel-Hashomer, Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel.
authors.forename: N
authors.initials: N
authors.lastname: Agmon-Levin
authors.forename: C
authors.initials: C
authors.lastname: Rosário
authors.forename: B-S Porat
authors.initials: BS
authors.lastname: Katz
authors.forename: G
authors.initials: G
authors.lastname: Zandman-Goddard
authors.forename: P
authors.initials: P
authors.lastname: Meroni
authors.forename: R
authors.initials: R
authors.lastname: Cervera
authors.forename: L
authors.initials: L
authors.lastname: Stojanovich
authors.forename: M
authors.initials: M
authors.lastname: Blank
authors.forename: Ss
authors.initials: S
authors.lastname: Pierangeli
authors.forename: S
authors.initials: S
authors.lastname: Praprotnik
authors.forename: E de
authors.initials: Ed
authors.lastname: Meis
authors.forename: L Parente
authors.initials: LP
authors.lastname: Seguro
authors.forename: A
authors.initials: A
authors.lastname: Ruffatti
authors.forename: V
authors.initials: V
authors.lastname: Pengo
authors.forename: A
authors.initials: A
authors.lastname: Tincani
authors.forename: A
authors.initials: A
authors.lastname: Doria
authors.forename: Y
authors.initials: Y
authors.lastname: Shoenfeld
mesh_terms: D000328:Adult; D017152:Antibodies, Antiphospholipid / Q000097:blood; D000913:Antibodies, Protozoan / Q000097:blood; D000914:Antibodies, Viral / Q000097:blood; D016736:Antiphospholipid Syndrome / Q000097:blood* / Q000150:complications / Q000175:diagnosis; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D002388:Catastrophic Illness; D005260:Female; D005293:Ferritins / Q000097:blood*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D012698:Serologic Tests; D015854:Up-Regulation
chemical_list: D017152:Antibodies, Antiphospholipid; D000913:Antibodies, Protozoan; D000914:Antibodies, Viral; D015415:Biomarkers; D005293:Ferritins
keywords: CMV; Ferritin; anti-cardiolipin; antiphospholipid syndrome; autoimmunity; catastrophic antiphospholipid syndrome; hyperferritinemia