Retrospective analysis of low-dose interleukin-2 therapy on chronic autoimmune thyroid disease with concurrent systemic lupus erythematosus

Abstract

Introduction

Low-dose interleukin-2 (IL-2) regulates the homeostasis of CD4⁺ T cells by modulating the proportions of effector and regulatory T cells, thus reducing disease activity in patients with systemic lupus erythematosus (SLE). However, to date, no research has been carried out on the efficacy of low-dose IL-2 for treating autoimmune thyroid disease (AITD). The aim of this study was to observe the effects of IL-2 on AITD patients with concurrent SLE, and explore potential mechanism of action.

Methods

A retrospective analysis was conducted on 29 SLE patients with concurrent AITD. Among them, 11 patients were in IL-2 therapy group and 18 patients without IL-2 treatment were considered as control group. Two groups had similar disease activities and were treated with comparable regular strategy. Free triiodothyronine (FT3), free thyroxine (FT4), thyroxine(T4), triiodothyronine(T3), thyroid stimulating hormone (TSH), thyroglobulin antibody (TG-Ab), thyroid peroxidase antibody (TPO-Ab) levels and immune cell subgroups were measured.

Results

After receiving low-dose IL-2 therapy, the TG-Ab and TPO-Ab levels decreased drastically (TG-Ab p = 0.008, TPO-Ab p = 0.007), and the majority of the AITD patients became seronegative, while there was no discernible change in control group. In IL-2 group, percentage of CD4⁺ T cells showed a significant increase after treatment (p = 0.029), with an upward trend in the ratio of regulatory T (Treg) cells to follicular helper T (Tfh) cells (Treg/Tfh). The percentage as well as absolute count of B cells demonstrated a decreasing trend.

Conclusion

Low-dose IL-2 may downregulate the levels of TG-Ab and TPO-Ab by modulating the immune balance of Treg/Tfh and B-cells, providing new avenue for clinical treatment of AITD.

Key Messages

• Low-dose IL-2 could decrease the levels of TG-Ab and TPO-Ab in AITD with concurrent SLE patients.

• Low-dose IL-2 may regulate Treg/Tfh balance and B-cells to ameliorate TG-Ab and TPO-Ab.

• Low-dose IL-2 provides a new avenue for AITD clinical treatment.

Keywords:

• Low-dose interleukin-2
• autoimmune thyroid disease
• therapy

Acknowledgments

We would like to thank all the patients, study investigators, and staff who were involved with this study.

Authors’ contributions

JH was involved in the conception and design. NW and YJ performed data analysis. NW, BH, YJ, GC and KZ were involved in the interpretation of the data. NW and YL drafted the paper, revised it critically for intellectual content. JH and YJ contributed to the final approval of the version to be published. All authors agree to be accountable for all aspects of the work.

Informed consent

Informed consent was obtained from all individuals included in this study.

Disclosure statement

The authors report no declarations of interest.

Data availability statement

The data that support the findings of this study are available from the corresponding author, Jing He, upon reasonable request.

Additional information

Funding

This work was supported by the National Key R&D Program of China (No. 2022YFE0131700), Beijing sci-Tech Program (Z191100006619114), National Natural Science Foundation of China (81701607, 82071813 and 8227183), and Peking University People’s Hospital Scientific Research Development Funds (RDZH2022-03).