Diverse effects on vaccine-specific serum IgG titres and memory B cells upon methotrexate and anti-TNF-α therapy in children with rheumatic diseases: A cross-sectional study

Vaccine. 2016 Mar 4;34(10):1304-11. doi: 10.1016/j.vaccine.2016.01.027. Epub 2016 Jan 29.


Objectives: We aimed at a comprehensive evaluation of how anti-TNF-α therapy and methotrexate treatment interferes with B cell memory in children with Paediatric Rheumatic Disease (PRD), by evaluating existing B cell phenotypes, and preserved vaccine-specific memory B cells and IgG titres generated prior to disease and treatment.

Methods: In a cross-sectional study on children with PRD on various treatments, we measured titre levels and avidity strength of serum IgG specific against measles, rubella and tetanus. We also quantified transitional B cells and resting, atypical, and activated memory B cells with flow cytometry, and enumerated antigen-specific memory B cells with ELISpot.

Results: For children who had received a tetanus booster, patients treated with any disease-modifying anti-rheumatic drug (DMARD) had lower tetanus serum IgG compared to healthy controls and NSAID-treated patients. Patients without a measles booster had lower levels of measles-specific memory B cells, but all vaccine-specific memory B cells were preserved in patients with booster. We furthermore found that the mature B cell compartment was phenotypically similar between patients and healthy controls.

Conclusions: We concluded that the general and vaccine-specific memory B cell compartment is well preserved in children with PRD and DMARD treatment, but that they might have lower serum tetanus IgG. We emphasize the importance for these children to follow the full vaccination schedule, and suggest to re-measure tetanus titres as they reach adulthood.

Keywords: Anti-TNF-α therapy; B-lymphocytes; MMR vaccine; Paediatric rheumatic disease; Tetanus toxoid vaccine.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Antibodies, Bacterial / blood
  • Antibodies, Viral / blood
  • Antirheumatic Agents / therapeutic use*
  • B-Lymphocytes / drug effects*
  • B-Lymphocytes / immunology
  • Case-Control Studies
  • Child
  • Child, Preschool
  • Cross-Sectional Studies
  • Diphtheria-Tetanus-Pertussis Vaccine / administration & dosage
  • Female
  • Humans
  • Immunization, Secondary
  • Immunoglobulin G / blood*
  • Immunologic Memory / drug effects*
  • Male
  • Measles / prevention & control
  • Measles-Mumps-Rubella Vaccine / administration & dosage
  • Methotrexate / therapeutic use*
  • Rubella / prevention & control
  • Tetanus / prevention & control
  • Tumor Necrosis Factor-alpha / antagonists & inhibitors*


  • Antibodies, Bacterial
  • Antibodies, Viral
  • Antirheumatic Agents
  • Diphtheria-Tetanus-Pertussis Vaccine
  • Immunoglobulin G
  • Measles-Mumps-Rubella Vaccine
  • Tumor Necrosis Factor-alpha
  • Methotrexate