Abstract: PO0608
Enabled ICOS+-RTE-Tresp Proliferation Is Involved in the Pathogenesis of Active Systemic Lupus Erythematosus (SLE)
Session Information
- CKD Mechanisms - 1
October 22, 2020 | Location: On-Demand
Abstract Time: 10:00 AM - 12:00 PM
Category: CKD (Non-Dialysis)
- 2103 CKD (Non-Dialysis): Mechanisms
Authors
- Kälble, Florian, Department of Medicine I (Nephrology), University of Heidelberg, Heidelberg, Germany
- Nusshag, Christian, Department of Medicine I (Nephrology), University of Heidelberg, Heidelberg, Germany
- Morath, Christian, Department of Medicine I (Nephrology), University of Heidelberg, Heidelberg, Germany
- Zeier, Martin G., Department of Medicine I (Nephrology), University of Heidelberg, Heidelberg, Germany
- Schaier, Matthias, Department of Medicine I (Nephrology), University of Heidelberg, Heidelberg, Germany
- Steinborn-Kroehl, Andrea, Department of Obstetrics and Gynecology, University of Heidelberg, Heidelberg, Germany
Background
Dysfunction of CD4+-regulatory-T-cells (Tregs) and CD4+-responder-T-cells (Tresps) is an important trigger in the development of active systemic lupus erythematosus. By now, underlying mechanisms are not fully understood.
Methods
To determine differences in the differentiation of inducible costimulatory molecule (ICOS)+- and ICOS--Tregs/Tresps, their percentages of CD45RA+CD31+-recent thymic emigrant (RTE)-Treg/Tresps and CD45RA+CD31-mature naïve (MN)-Treg/Tresps as well as CD45RA-CD31+ and CD45RA-CD31--memory-Treg/Tresps (CD31+- and CD31--memory Treg/Tresps) within total Tregs/Tresps were calculated. Additionally, subsets were stained for the proliferation marker Ki67. 124 healthy control patients and 117 with a preexisting lupus erythematosus (102 patients in remission, 15 patients with a flare) were measured.
Results
SLE patients in remission show an increased differentiation of ICOS+-RTE-Tregs and ICOS--RTE-Tregs via resting MN-Tregs into CD31--memory-Tregs compared to healthy control patients. In contrast, proliferation of ICOS+-RTE-Tresps into ICOS+CD31--memory-Tresps is inhibited. Similarly, active SLE patients show an increased differentiation of ICOS+-RTE-Tregs and ICOS--RTE-Tregs via resting MN-Tregs. Moreover, proliferation ability of ICOS+-RTE-Tresps is not inhibited but enabled in these patients.
Both SLE patients in remission and active SLE patients show an impaired ICOS--RTE-Tresp differentiation compared to healthy control patients.
Hence, the ratio of ICOS--Tregs/ICOS--Tresps within CD4+-T-cells is significantly increased in both SLE remission and active SLE patients compared to healthy control patients. In contrast, the ratio of ICOS+-Tregs/ICOS+-Tresps is significantly increased in SLE remission patients, but decreased in active SLE patients compared to healthy control patients.
Conclusion
Proliferation of ICOS+-RTE-Tresps is medically inhibited in SLE remission patients. In active SLE patients, proliferation is enabled decreasing the ICOS+-Treg/ICOS+-Tresp ratio.