Background/Purpose: Behcet’s disease (BD) is a chronic multisystemic disease characterized by muco-cutaneous and ocular manifestations, with central nervous system, vascular and/or gastro-intestinal involvement. Several studies have shown that immune mechanisms play an important role in the development of the disease and limited options of therapeutic medicines for BD. Low dose IL-2 has been reported to selectively promote the expansion of Treg. This study aimed to investigate the significance of Treg cells in the pathogenesis and the effect of low dose IL-2 on BD.

Methods: Absolute number of CD4+CD25+FOXP3+Treg, CD4+IL17+T (Th17) and other subsets in peripheral blood (PB) from 173 patients with BD and 90 healthy donors were characterized by flow cytometry combined with an internal microsphere counting standard. Thirty-nine patients were treated with daily subcutaneous injections of 0.5 million IU of human IL-2 for five consecutive days, and then its effects on lymphocyte subpopulations in PB were analyzed.

Results: There was a significant disturbance in lymphocyte subpopulations mainly manifested as the decreased level of Tregs compared with the health controls (median:22.32 cells/ul VS median:33.12 cells/ul, P< 0.001) and it was correlated negatively with BDCAF, ESR and CRP (P < 0.01), suggesting an important role of Tregs in sustained high disease activity. While no major difference in the absolute counts of circulating Th17 cells between patients with BD and health control. Accordingly, the ratios of Th17/Treg in patients with BD (median:0.38) were significantly higher than those of health control (median:0.21). Moreover, low dose IL-2 effectively increased the number of Tregs (P < 0.001) and re-balance the ratio of Th17 and Tregs, leading to clinic symptom partly remission in a rapid way without observed side effects.There was a significant disturbance in lymphocyte subpopulations mainly manifested as the decreased level of Tregs compared with the health controls (median:22.32 cells/ul VS median:33.12 cells/ul, P< 0.001) and it was correlated negatively with BDCAF, ESR and CRP (P < 0.01), suggesting an important role of Tregs in sustained high disease activity. While no major difference in the absolute counts of circulating Th17 cells between patients with BD and health control. Accordingly, the ratios of Th17/Treg in patients with BD (median:0.38) were significantly higher than those of health control (median:0.21). Moreover, low dose IL-2 effectively increased the number of Tregs (P < 0.001) and re-balance the ratio of Th17 and Tregs, leading to clinic symptom partly remission in a rapid way without observed side effects.

Conclusion: Absolute decrease of PB Tregs in patients with BD was associated with disease activity ,which might be the major reason for imbalance of Th17/Tregs. It is speculated that BD is an autoimmune disease triggered by the defect of immunotolerance. More importantly, low-dose IL-2 proposes a selective biological treatment strategy by restoring immune tolerance and promoting rapidly remission.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/low-dose-il-2-effectively-restored-decreased-regulatory-t-cells-in-patients-with-behcets-disease/