title: Pandemic influenza immunization in primary antiphospholipid syndrome (PAPS): a trigger to thrombosis and autoantibody production?
abstract: OBJECTIVE
  The objective of this report is to conduct short- and long-term evaluation of a large panel of antiphospholipid (aPL) autoantibodies following pandemic influenza A/H1N1 non-adjuvant vaccine in primary antiphospholipid syndrome (PAPS) patients and healthy controls.
  
  
  METHODS
  Forty-five PAPS and 33 healthy controls were immunized with H1N1 vaccine. They were prospectively assessed at pre-vaccination, and three weeks and six months after vaccination. aPL autoantibodies were determined by an enzyme-linked immunosorbent assay (ELISA) and included IgG/IgM: anticardiolipin (aCL), anti-beta2glycoprotein I (anti-β2GPI); anti-annexin V, anti-phosphatidyl serine and anti-prothrombin antibodies. Anti-Sm was determined by ELISA and anti-double-stranded DNA (anti-dsDNA) by indirect immunofluorescence. Arterial and venous thrombosis were also clinically assessed.
  
  
  RESULTS
  Pre-vaccination frequency of at least one aPL antibody was significantly higher in PAPS patients versus controls (58% vs. 24%, p = 0.0052). The overall frequencies of aPL antibody at pre-vaccination, and three weeks and six months after immunization remained unchanged in patients (p = 0.89) and controls (p = 0.83). The frequency of each antibody specificity for patients and controls remained stable in the three evaluated periods (p > 0.05). At three weeks, two PAPS patients developed a new but transient aPL antibody (aCL IgG and IgM), whereas at six months new aPL antibodies were observed in six PAPS patients and none had high titer. Anti-Sm and anti-dsDNA autoantibodies were uniformly negative and no new arterial or venous thrombosis were observed throughout the study.
  
  
  CONCLUSIONS
  This is the first study to demonstrate that pandemic influenza vaccine in PAPS patients does not trigger short- and long-term thrombosis or a significant production of aPL-related antibodies (ClinicalTrials.gov, #NCT01151644).
authors: Division of Rheumatology and.
authors: D Martins
authors: DM
authors: de Medeiros
authors: Division of Rheumatology and Pediatric Rheumatology Unit, Faculdade de Medicina da Universidade de São Paulo, São Paulo.
authors: C A
authors: CA
authors: Silva
authors: Division of Rheumatology and.
authors: C
authors: C
authors: Bueno
authors: Division of Rheumatology and.
authors: A C Medeiros
authors: AC
authors: Ribeiro
authors: Division of Rheumatology and.
authors: V dos Santos T
authors: Vdos S
authors: Viana
authors: Division of Rheumatology, Universidade Federal da Bahia, Bahia, Brazil.
authors: J Freire
authors: JF
authors: Carvalho
authors: Division of Rheumatology and eloisa.bonfa@hc.fm.usp.br.
authors: E
authors: E
authors: Bonfa
mesh_terms: D000328:Adult; D017304:Annexin A5 / Q000276:immunology; D017153:Antibodies, Anticardiolipin / Q000097:blood; D000974:Antibodies, Antinuclear / Q000097:blood; D017152:Antibodies, Antiphospholipid / Q000097:blood*; D016736:Antiphospholipid Syndrome / Q000097:blood*; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D007075:Immunoglobulin M / Q000097:blood; D053118:Influenza A Virus, H1N1 Subtype / Q000276:immunology; D007252:Influenza Vaccines / Q000009:adverse effects / Q000276:immunology*; D007251:Influenza, Human / Q000453:epidemiology* / Q000517:prevention & control* / Q000821:virology; D008297:Male; D008875:Middle Aged; D058873:Pandemics; D010718:Phosphatidylserines / Q000276:immunology; D011446:Prospective Studies; D011516:Prothrombin / Q000276:immunology; D013927:Thrombosis / Q000139:chemically induced; D013997:Time Factors; D014611:Vaccination / Q000009:adverse effects
chemical_list: D017304:Annexin A5; D017153:Antibodies, Anticardiolipin; D000974:Antibodies, Antinuclear; D017152:Antibodies, Antiphospholipid; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D007252:Influenza Vaccines; D010718:Phosphatidylserines; D011516:Prothrombin
keywords: H1N1; Vaccine; antiphospholipid antibodies; antiphospholipid syndrome; pandemic influenza A