The immunogenicity of seasonal and pandemic influenza vaccination in autoimmune inflammatory rheumatic patients—a 6-month follow-up prospective study

  • K. LakotaEmail author
  • K. Perdan-Pirkmajer
  • S. Sodin-Šemrl
  • S. Čučnik
  • V. Šubelj
  • K. Prosenc
  • K. Mrak Poljšak
  • M. Tomšič
  • A. Ambrožič
  • S. Praprotnik
Original Article
Part of the following topical collections:
  1. Autoimmune Collection 2018



Influenza may cause severe complications in patients with autoimmune inflammatory rheumatic disease (AIRD), to whom vaccinations are especially recommended. However, AIRD patients require cautious scrutiny of immunogenicity as they might exhibit poor antibody response to vaccination, especially when taking immunomodulatory medications.


The aim was to determine immunogenicity of seasonal and pandemic influenza vaccine in AIRD patients, its timeline/persistence, and influence of medications on immune response.


One hundred and thirty-seven AIRD and 54 healthy controls were vaccinated with trivalent seasonal influenza. After 3–5 weeks, 15 healthy controls and 93 AIRD were vaccinated with pandemic influenza vaccine, and 63 of patients were vaccinated a second time after 3–5 weeks. Sera were collected before vaccination, 18–90 days after each vaccination, and more than 180 days after the last vaccination. The immune response was measured using hemagglutination inhibition (HI) assay and IgG/IgA antibodies against influenza A/B with ELISA.


Our findings indicate that following vaccination with seasonal influenza vaccine, seroprotection, seroresponse, and change in geometric mean titers (GMT) in AIRD patients was not compromised compared to healthy. Similarly, we report for pandemic influenza vaccination little added benefit of the second dose. We confirm lowest increase in HI titer in rituximab-treated AIRD compared to other medications. Vaccination largely tilts the balance from negative ELISA A IgG and IgA titers to positive titers in seasonal H1N1 seroresponsive AIRD patients and controls. A significant decrease in HI GMT and seroprotection was observed only in AIRD at > 180 days after vaccination highlighting an absent persistence of immunogenic response in AIRD patients. Due to high initial HI titers for influenza vaccine, we foresee their benefit in personalized medicine in the future.


Influenza vaccination is immunologically active for AIRD, with little value of the second dose of the pandemic vaccine and further scrutiny on persistence of immune response to vaccine in AIRD is needed.


Autoimmune inflammatory rheumatic disease Influenza Pandemic Seasonal Vaccination 



Many thanks to the Blood Transfusion Centre of Slovenia for donating human 0 type erythrocytes for HI testing and WHO Collaborating Centre for Reference and Research on Influenza in London for providing the reference influenza viruses and antisera.

Funding information

This work was funded by the Slovene Research Agency (ARRS) for the National Research Programme #P3-0314.

Compliance with ethical standards

Ethical approval for the study was obtained from the National Medical Ethics Committee of Slovenia (#122/09/09), and the study was conducted according to the principles outlined in the Declaration of Helsinki. All participants signed an informed consent.



Supplementary material

10067_2019_4439_MOESM1_ESM.docx (16 kb)
ESM 1 (DOCX 16.1 kb)


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Copyright information

© International League of Associations for Rheumatology (ILAR) 2019

Authors and Affiliations

  1. 1.Department of RheumatologyUniversity Medical Centre LjubljanaLjubljanaSlovenia
  2. 2.Faculty of Mathematics, Natural Science and Information TechnologiesUniversity of PrimorskaKoperSlovenia
  3. 3.Chair of PharmacyUniversity of LjubljanaLjubljanaSlovenia
  4. 4.Laboratory for public health virologyNational Laboratory for Health, Environment and FoodLjubljanaSlovenia
  5. 5.Faculty of MedicineUniversity of LjubljanaLjubljanaSlovenia

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