The Role of Regulatory T and B Cells in the Etiopathogenesis of Idiopathic Granulomatous Mastitis

ABSTRACT

Background and objectives

The aim of this study was to evaluate the role of T- and B-regulatory cells (Tregs and Bregs) in the pathogenesis of idiopathic granulomatous mastitis (IGM).

Methods

This study includes 47 patients with pathologically proven IGM (Group P) and 26 healthy subjects (Group C). The patients in Group P were divided into two groups according to whether their lesions were active (Group P_A, n: 21) or in remission (Group P_R, n: 26). By using flow-cytometry, the frequencies of CD3⁺CD4⁺CD45RA⁻Foxp3^high activated Tregs (aTregs), CD3⁺CD4⁺CD45RA⁻Foxp3^low non-suppressive Tregs, CD3⁺CD4⁺CD45RA⁺Foxp3^low resting Tregs (rTregs), CD3⁺CD4⁺CD25⁺Foxp3⁻ T-effector cells (Teff), total Tregs and Bregs were analyzed in all subjects.

Results

The frequency of the Teff cells was statistically higher in Group P when compared with Group C (p =.004). The Foxp3 expression of Treg cells and the frequency of non-suppressive Tregs in Group P were statistically lower than Group C (p =.032 and p =.02, respectively). In addition, Group P_R’s Foxp3 expressions were statistically lower than Group C (p =.027); Group P_R’s aTregs ratio was statistically lower than Group P_A (p =.021); and the non-suppressive Tregs ratio of Group P_R was lower than both Group P_A and Group C (p =.006 and p <.0001). No significant differences were seen Bregs and B cell subsets.

Conclusion

Significant changes in Foxp3 expression and Treg subsets were seen in patients with active IGM lesion and in remission. This study shows an intrinsic defect of Tregs in patients with IGM.

KEYWORDS:

• B regulatory cells
• T regulatory cells
• idiopathic granulomatous mastitis
• etiopathogenesis

Acknowledgments

Hulya Ucaryilmaz and Hande Koksal, contributed equally to the article.

Disclosure statement

The authors have no conflicts of interests to declare.

Author contributions

H.U., H.K., A.E., N.K., J.M.D., performed the research. H.K., H.U., and H.A. designed this study. H.K., H.U., N.K. J.M.D., and H.A. analyzed the data. H.K. followed up the patients. H.U. H.K. A.E., N.K. J.M.D and H.A. wrote this paper. H.U., H.K., N.K., J.M.D., and H.A. provided advice and critical discussions on the project. All of the authors read and approved the final version of this paper.

Statement of ethics

This study was approved by the Ethical Committee of Selcuk University Medical Faculty (No: 050.01.04/10933). Written informed consent was obtained from all patients and all volunteer healthy participants.

List of all abbreviations

IGM: idiopathic granulomatous mastitis

M: mean

Mdn: median

SD: standard deviation

Q: quartile

Tregs: Regulatory T cells

aTregs: activated Tregs

rTregs: resting Tregs

Bregs: Regulatory B cells

Teff: Effector T cells

CD: cluster of differentiation

IL: interleukin

Additional information

Funding

This study was supported by the Scientific Research Projects of Selcuk University [Project No: 19401056].