Background/Purpose: T regulatory cells (Treg) play a crucial role in the regulation of the immune response and therefore are of utmost interest when studying autoimmune diseases, such as rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). Therefore, targeting specific Treg markers in therapy is now widely discussed. Expression of T cell immunoglobulin 3 (TIM-3) is associated with an enhanced immune suppression and is currently discussed as target in cancer therapy. Fc receptor-like protein 3 (FCLR-3), which regulates Treg proliferation, was shown to be associated with the susceptibility in juvenile RA. Other surface markers, like CD161 enable Treg to produce IL-17A, IFNγ and IL-2, hence promoting inflammation. The aim of this study was to distinguish between RA and SLE using anti-and pro-inflammatory cell markers.

Methods: Peripheral blood samples from 66 patients suffering from RA (mean ± SD; age 60 ± 10 years, female ratio: 0.68, disease duration 18 ± 14 years), 40 SLE patients (age 42 ± 13 years, female ratio 0.85, disease duration 11 ± 13 years) and 72 age-matched healthy participants (age 46 ± 17 years, female ratio 0.68) were drawn over a sampling period of two years. Freshly isolated PBMCs were stained and Treg subsets were identified by the expression of CD25, CD127, FoxP3, CD45RA and CD15 on the surface of CD3⁺CD4⁺ T cells. CD25⁺CD127⁺CD45^– Treg were further subclassified by the expression of TIM-3 (CD366) and FCLR-3 (CD307c). CD161 was used to identify Th17 type Treg (CD15S^–CD161^–) and transitional Treg (CD15S^–CD161^–). All cytometric measurements were performed using a standardized BD LSR Fortessa platform.

Results: Transitional Treg (CD15S^–CD161^–) were significantly higher (p < 0.001) in RA patients compared to the SLE and healthy cohort (40.5 ± 13.4% vs. 28.7 ± 9.6% and 29.7 ± 9.4% respectively). However, differences in the CD161⁺ Th17 type Treg population could not be detected. Treg expressing TIM-3 were higher in both RA and SLE patients compared to healthy controls (2.8 ± 2.3%, p = 0.0105 and 2,.6 ± 1.6%, p = 0.0031 vs. 0.8 ± 0.7% respectively), but did not differ between the rheumatic diseases. On the other hand, FCLR-3 positive Treg distinguished RA and SLE patients (17.8 ± 13.3 vs. 25.3 ± 13.1%, p = 0.0036), as well as SLE patients from healthy controls (16.8 ± 12.9%, p = 0.0112). All findings were not correlated with the disease activity of RA or SLE patients.

Conclusion: Expression of the negative immune checkpoint molecules TIM-3 and FCRL-3 not only distinguish healthy controls from patients suffering from RA or SLE but can be used to differentiate between different autoimmune diseases. These findings indicate that the regulation of the immune response in RA and SLE is triggered by Treg, yet the activation of different Treg subset is disease-specific.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/negative-immune-checkpoint-molecules-on-t-regulator-cells-distinguish-ra-sle-and-healthy-controls/