Pandemic influenza immunization in primary antiphospholipid syndrome (PAPS): a trigger to thrombosis and autoantibody production?

Lupus. 2014 Nov;23(13):1412-6. doi: 10.1177/0961203314540351. Epub 2014 Jun 24.


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 (, #NCT01151644).

Keywords: H1N1; Vaccine; antiphospholipid antibodies; antiphospholipid syndrome; pandemic influenza A.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Annexin A5 / immunology
  • Antibodies, Anticardiolipin / blood
  • Antibodies, Antinuclear / blood
  • Antibodies, Antiphospholipid / blood*
  • Antiphospholipid Syndrome / blood*
  • Case-Control Studies
  • Female
  • Humans
  • Immunoglobulin G / blood
  • Immunoglobulin M / blood
  • Influenza A Virus, H1N1 Subtype / immunology
  • Influenza Vaccines / adverse effects
  • Influenza Vaccines / immunology*
  • Influenza, Human / epidemiology*
  • Influenza, Human / prevention & control*
  • Influenza, Human / virology
  • Male
  • Middle Aged
  • Pandemics*
  • Phosphatidylserines / immunology
  • Prospective Studies
  • Prothrombin / immunology
  • Thrombosis / chemically induced
  • Time Factors
  • Vaccination / adverse effects


  • Annexin A5
  • Antibodies, Anticardiolipin
  • Antibodies, Antinuclear
  • Antibodies, Antiphospholipid
  • Immunoglobulin G
  • Immunoglobulin M
  • Influenza Vaccines
  • Phosphatidylserines
  • Prothrombin

Associated data