title: Value of isolated IgA anti-β2 -glycoprotein I positivity in the diagnosis of the antiphospholipid syndrome.
abstract: OBJECTIVE
  To examine the prevalence of isolated IgA anti-β2 -glycoprotein I (anti-β2 GPI) positivity and the association of these antibodies, and a subgroup that bind specifically to domain IV/V of β2 GPI, with clinical manifestations of the antiphospholipid syndrome (APS) in 3 patient groups and to evaluate the pathogenicity of IgA anti-β2 GPI in a mouse model of thrombosis.
  
  
  METHODS
  Patients with systemic lupus erythematosus (SLE) from a multiethnic, multicenter cohort (LUpus in MInorities, NAture versus nurture [LUMINA]) (n = 558), patients with SLE from the Hopkins Lupus Cohort (n = 215), and serum samples referred to the Antiphospholipid Standardization Laboratory (APLS) (n = 5,098) were evaluated. IgA anti-β2 GPI titers and binding to domain IV/V of β2 GPI were examined by enzyme-linked immunosorbent assay (ELISA). CD1 mice were inoculated with purified IgA anti-β2 GPI antibodies, and surgical procedures and ELISAs were performed to evaluate thrombus development and tissue factor (TF) activity.
  
  
  RESULTS
  A total of 198 patients were found to be positive for IgA anti-β2 GPI isotype, and 57 patients were positive exclusively for IgA anti-β2 GPI antibodies. Of these, 13 of 23 patients (56.5%) in the LUMINA cohort, 17 of 17 patients (100%) in the Hopkins cohort, and 10 of 17 patients (58.9%) referred to APLS had at least one APS-related clinical manifestation. Fifty-four percent of all the IgA anti-β2 GPI-positive serum samples reacted with domain IV/V of anti-β2 GPI, and 77% of those had clinical features of APS. Isolated IgA anti-β2 GPI positivity was associated with an increased risk of arterial thrombosis (P < 0.001), venous thrombosis (P = 0.015), and all thrombosis (P < 0.001). The association between isolated IgA anti-β2 GPI and arterial thrombosis (P = 0.0003) and all thrombosis (P = 0.0003) remained significant after adjusting for other risk factors for thrombosis. In vivo mouse studies demonstrated that IgA anti-β2 GPI antibodies induced significantly larger thrombi and higher TF levels compared to controls.
  
  
  CONCLUSIONS
  Isolated IgA anti-β2 GPI-positive titers may identify additional patients with clinical features of APS. Testing for these antibodies when other antiphospholipid tests are negative and APS is suspected is recommended. IgA anti-β2 GPI antibodies directed to domain IV/V of β2 GPI represent an important subgroup of clinically relevant antiphospholipids.
authors: University of Texas Medical Branch, Galveston.
authors: Vijaya
authors: V
authors: Murthy
authors: Rohan
authors: R
authors: Willis
authors: Zurina
authors: Z
authors: Romay-Penabad
authors: Patricia
authors: P
authors: Ruiz-Limón
authors: Laura A
authors: LA
authors: Martínez-Martínez
authors: Shraddha
authors: S
authors: Jatwani
authors: Praveen
authors: P
authors: Jajoria
authors: Alan
authors: A
authors: Seif
authors: Graciela S
authors: GS
authors: Alarcón
authors: Elizabeth
authors: E
authors: Papalardo
authors: Jigna
authors: J
authors: Liu
authors: Luis M
authors: LM
authors: Vilá
authors: Gerald
authors: G
authors: McGwin
authors: Terry A
authors: TA
authors: McNearney
authors: Rashmi
authors: R
authors: Maganti
authors: Prashanth
authors: P
authors: Sunkureddi
authors: Trisha
authors: T
authors: Parekh
authors: Michael
authors: M
authors: Tarantino
authors: Ehtisham
authors: E
authors: Akhter
authors: Hong
authors: H
authors: Fang
authors: Emilio B
authors: EB
authors: Gonzalez
authors: Walter R
authors: WR
authors: Binder
authors: Gary L
authors: GL
authors: Norman
authors: Zakera
authors: Z
authors: Shums
authors: Marius
authors: M
authors: Teodorescu
authors: John D
authors: JD
authors: Reveille
authors: Michelle
authors: M
authors: Petri
authors: Silvia S
authors: SS
authors: Pierangeli
mesh_terms: D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000097:blood*; D016736:Antiphospholipid Syndrome / Q000097:blood / Q000175:diagnosis* / Q000276:immunology; D001323:Autoantibodies / Q000097:blood*; D006801:Humans; D007070:Immunoglobulin A / Q000097:blood*; D008137:Longitudinal Studies; D051379:Mice; D015995:Prevalence; D013927:Thrombosis / Q000175:diagnosis / Q000276:immunology; D053482:beta 2-Glycoprotein I / Q000276:immunology*
chemical_list: D000888:Antibodies, Anti-Idiotypic; D001323:Autoantibodies; D007070:Immunoglobulin A; C049937:anti-IgA; D053482:beta 2-Glycoprotein I
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