Control of humoral immunity and auto-immunity by the CXCR4/CXCL12 axis in lupus patients following influenza vaccine

Vaccine. 2013 Aug 2;31(35):3492-501. doi: 10.1016/j.vaccine.2013.05.095. Epub 2013 Jun 11.


Background: CXCR4 is a chemokine receptor with multiple effects on the immune system, upregulated in patients with SLE, and correlated with disease severity.

Objective: This study has investigated whether the levels of CXCR4 expressed on leucocyte subsets in lupus patients are correlated with the efficacy and the safety of the influenza vaccine.

Methods: Twenty-seven patients were vaccinated and vaccine immunogenicity and tolerance were evaluated. CXCR4 was assayed on leucocyte subsets and correlated with clinical and immunological signs of diseases activity.

Results: A significant increase in the titres of antibodies to the three viral strains was observed along with trends towards an increased vaccine efficacy in patients with quiescent disease vs patients with active disease. Recent flu vaccine history and, to a lesser extent, immunosuppressive treatment may influence vaccine immunogenicity. Influenza immunization was not associated with clinical side-effects or clinical lupus flare but with an increase in rheumatoid factor levels. Our study also confirms the correlation of CXCR4 expression with biological autoimmunity as shown by the correlation between the percentage of CXCR4-positive T cells and the ANA titres at D0, and the reverse correlation between CXCR4 expression and vaccine immunogenicity as demonstrated by the higher percentage of CXCR4-positive T cells at D0 and D30 in non-responders vs responders.

Conclusion: Altogether, our study confirms the efficacy and the safety of flu vaccine in SLE patients, highlights the role of CXCR4 as a surrogate marker for autoimmunity in lupus and shows that CXCR4 expression on T cells is predictive of vaccine efficacy in SLE patients.

Trial registration: NCT01072734.

Keywords: CXCR4; Influenza; Leucocytes; Systemic lupus erythematosus; Vaccine.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antibodies, Viral / blood
  • Antibody Formation / immunology
  • Chemokine CXCL12 / biosynthesis
  • Chemokine CXCL12 / immunology*
  • Female
  • Humans
  • Immunity, Humoral / immunology
  • Influenza Vaccines / adverse effects
  • Influenza Vaccines / immunology*
  • Influenza Vaccines / therapeutic use
  • Influenza, Human / immunology*
  • Influenza, Human / prevention & control
  • Interferon-alpha / blood
  • Lupus Erythematosus, Systemic / immunology*
  • Lupus Erythematosus, Systemic / metabolism
  • Male
  • Middle Aged
  • Prospective Studies
  • Receptors, CXCR4 / biosynthesis
  • Receptors, CXCR4 / immunology*
  • T-Lymphocytes / immunology
  • T-Lymphocytes / metabolism
  • Vaccination


  • Antibodies, Viral
  • CXCL12 protein, human
  • CXCR4 protein, human
  • Chemokine CXCL12
  • Influenza Vaccines
  • Interferon-alpha
  • Receptors, CXCR4

Associated data