(99) Tc-methylene diphosphonate improves rheumatoid arthritis disease activity by increasing the frequency of peripheral γδ T cells and CD4(+) CD25(+) Foxp3(+) Tregs.
OBJECTIVE
γδ T cells exhibit important functions in the pathogenesis of rheumatoid arthritis (RA). In recent years, numerous studies harnessed the γδ T cell-activating capacity of aminobiphosphonates for the treatment of malignant tumors. As (99) Tc-methylene diphosphonate ((99) Tc-MDP) has long been widely used for the treatment of RA in China with good efficacy, we are interested in whether this drug exerts its therapeutic effect on RA by modulating peripheral γδ T cells of RA patients.


OBJECTIVE
To investigate the effect of (99) Tc-MDP on the frequency of γδ T cells and CD4(+) CD25(+) Foxp3(+) Tregs in the peripheral blood of patients with active RA.


METHODS
Nineteen patients with active RA were treated with (99) Tc-MDP intravenously at a dose of 20 μg/day consecutively for 10-14 days. Before and after treatment, the main clinical and laboratory parameters for each patient were evaluated. The frequency of CD3(+) γδ(+) T cells and CD4(+) CD25(+) Foxp3(+) Tregs was detected by flow cytometry. Serum levels of interferon (IFN)-γ, tumor necrosis factor (TNF)-α, interleukin (IL)-6, IL-10 and transforming growth factor (TGF)-β were measured with enzyme-linked immunosorbent assay.


RESULTS
After intravenous (99) Tc-MDP therapy, the frequency of peripheral CD3(+) γδ(+) T cells and CD4(+) CD25(+) Foxp3(+) Tregs were significantly elevated, paralleled with decreased serum levels of TNF-α and IL-6 and increased level of serum TGF-β. The elevation of peripheral CD3(+) γδ(+) T cells was positively correlated with increased serum TGF-β and decreased disease activity.


CONCLUSIONS
(99) Tc-MDP may improve the activity of RA through upregulating the frequency of peripheral γδ T cells and CD4(+) CD25(+) Foxp3(+) Tregs as well as affecting the serum cytokine environment by increasing TGF-β and decreasing TNF-α and IL-6.
Department of Rheumatology and Immunology, Nanjing First Hospital, Nanjing Medical University, Nanjing, China.
Dinglei
D
Su
Department of Rheumatology and Immunology, Nanjing First Hospital, Nanjing Medical University, Nanjing, China.
Minning
M
Shen
Department of Rheumatology and Immunology, Nanjing First Hospital, Nanjing Medical University, Nanjing, China.
Bingjie
B
Gu
Department of Rheumatology and Immunology, Nanjing First Hospital, Nanjing Medical University, Nanjing, China.
Xiaoqin
X
Wang
Department of Immunology and Rheumatology, Drum Tower Clinical Medical College of Nanjing Medical University, Nanjing, China.
Dandan
D
Wang
Department of Immunology, Dalian Medical University, Dalian, China.
Xia
X
Li
Department of Immunology and Rheumatology, Drum Tower Clinical Medical College of Nanjing Medical University, Nanjing, China.
Lingyun
L
Sun
D061605:Administration, Intravenous; D000368:Aged; D001172:Arthritis, Rheumatoid / Q000097:blood / Q000000981:diagnostic imaging / Q000276:immunology / Q000532:radiotherapy*; D016022:Case-Control Studies; D016207:Cytokines / Q000097:blood / Q000276:immunology; D004334:Drug Administration Schedule; D005260:Female; D051858:Forkhead Transcription Factors / Q000097:blood / Q000276:immunology*; D006801:Humans; D053645:Interleukin-2 Receptor alpha Subunit / Q000097:blood / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D019275:Radiopharmaceuticals / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000097:blood / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000378:metabolism / Q000528:radiation effects*; D013669:Technetium Tc 99m Medronate / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D013997:Time Factors; D016896:Treatment Outcome
D016207:Cytokines; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; C508017:IL2RA protein, human; D053645:Interleukin-2 Receptor alpha Subunit; D019275:Radiopharmaceuticals; D016692:Receptors, Antigen, T-Cell, gamma-delta; D013669:Technetium Tc 99m Medronate
99Tc-methylene diphosphonate (99Tc-MDP); cytokine; regulatory T cells (Treg); rheumatoid arthritis; γδ T cells