title: Seronegative antiphospholipid syndrome.
abstract: APS is an autoimmune disease that leads to arterial and/or venous thrombosis, recurrent pregnancy loss and persistently positive aPLs. Patients with clinical manifestations highly suggestive of APS but persistently negative conventional aPLs are classified as having seronegative APS. Ongoing research has revealed the existence of non-criteria antibodies proposed to be relevant to APS and that can be potentially included in the disease's classification criteria. We present a literature review on the most promising antibodies of this heterogeneous aPL family, which includes antibodies to a zwitterionic phospholipid, namely phosphatidylethanolamine, phospholipid-binding plasma proteins, phospholipid-protein complexes and anionic phospholipids other than cardiolipin. Although these molecules can increase the diagnostic yield of APS, their clinical relevance is still debatable and needs to be confirmed by interlaboratory efforts toward standardizing diagnostic tools, in addition to experimental data and larger longitudinal studies.
authors.affiliation: Department of Internal Medicine, American University of Beirut Medical Center, PO Box 11-0236, Riad El-Solh, Beirut 1107 2020, Lebanon.
authors.forename: Rabih
authors.initials: R
authors.lastname: Nayfe
authors.forename: Imad
authors.initials: I
authors.lastname: Uthman
authors.forename: Jessica
authors.initials: J
authors.lastname: Aoun
authors.forename: Ehab
authors.initials: E
authors.lastname: Saad Aldin
authors.forename: Mira
authors.initials: M
authors.lastname: Merashli
authors.forename: Munther A
authors.initials: MA
authors.lastname: Khamashta
mesh_terms: D017304:Annexin A5 / Q000276:immunology; D017152:Antibodies, Antiphospholipid / Q000097:blood / Q000276:immunology*; D000918:Antibody Specificity; D016736:Antiphospholipid Syndrome / Q000175:diagnosis / Q000276:immunology*; D002308:Cardiolipins / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology; D007075:Immunoglobulin M / Q000276:immunology; D008180:Lupus Erythematosus, Systemic / Q000175:diagnosis / Q000276:immunology*; D008297:Male; D010714:Phosphatidylethanolamines / Q000276:immunology*; D011247:Pregnancy; D011250:Pregnancy Complications, Hematologic / Q000276:immunology; D011379:Prognosis; D018570:Risk Assessment; D012698:Serologic Tests; D012720:Severity of Illness Index; D053482:beta 2-Glycoprotein I / Q000276:immunology*
chemical_list: D017304:Annexin A5; D017152:Antibodies, Antiphospholipid; D002308:Cardiolipins; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D010714:Phosphatidylethanolamines; D053482:beta 2-Glycoprotein I; C483858:phosphatidylethanolamine
keywords: anti-β2 glycoprotein I antibodies; antiphospholipid antibodies; antiphospholipid syndrome; phosphatidylethanolamine; pregnancy morbidity; seronegative antiphospholipid syndrome; thrombosis