Lymphocyte transformation test is not helpful for the diagnosis of methotrexate-induced pneumonitis in patients with rheumatoid arthritis

Clin Chim Acta. 2009 Sep;407(1-2):25-9. doi: 10.1016/j.cca.2009.06.024. Epub 2009 Jun 25.


Background: The pathophysiology underlying methotrexate (MTX)-induced pneumonitis has been considered as a hypersensitive reaction. The lymphocyte transformation test (LTT) is frequently used to detect hypersensitivity. Whereas previous reports have proposed that the LTT is not ideal to detect hypersensitivity to MTX, it has not been directly confirmed.

Methods: Forty rheumatoid arthritis (RA) patients (24 patients currently taking MTX and 16 patients with a past history of MTX administration) and 13 healthy subjects were recruited. LTT with MTX was used to assess thymidine incorporation. An MTS (3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium, inner salt) assay was also performed. The mitogenic activity was expressed as the Stimulatory Index (SI). The activity of RA was assessed by the disease activity score 28 (DAS28).

Results: In the presence of MTX, the SI measured by the LTT and by the MTS assay showed an inverse correlation. The presence of MTX significantly elevated the SI values measured by the LTT. However, the SI values were significantly lower in RA patients currently taking MTX than those of patients not currently taking MTX, although DAS28 was not different. Furthermore, a past history of MTX-induced pneumonitis did not affect the SI values.

Conclusion: LTT with MTX in RA patients is not appropriate to detect MTX-induced pneumonitis.

MeSH terms

  • Arthritis, Rheumatoid / drug therapy*
  • Arthritis, Rheumatoid / immunology
  • Arthritis, Rheumatoid / metabolism
  • Case-Control Studies
  • Cell Proliferation / drug effects
  • Humans
  • Lymphocyte Activation / drug effects*
  • Methotrexate / adverse effects*
  • Pneumonia / chemically induced*
  • Pneumonia / diagnosis*
  • Pneumonia / immunology
  • Pneumonia / metabolism
  • Reproducibility of Results
  • Tetrazolium Salts / metabolism
  • Thiazoles / metabolism
  • Time Factors


  • Tetrazolium Salts
  • Thiazoles
  • 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium
  • Methotrexate