Survivin supports insulin resistance of T cells and promotes development of rheumatoid arthritis.

Maria Bokarewa, Göteborgs universitet, 150000

Bakgrund och motivering

Several cross-sectional studies reported prevalent insulin resistance in RA patients, but the role of insulin in the autoimmune diseases was unexplored.

We reported a dual role of insulin resistance in RA. It has anti-inflammatory properties and efficiently alleviates arthritis. Also, it promotes autoimmunity and autoantibody production. Thus, we propose that insulin resistance of T cells helps bypassing the initial anti-inflammatory properties of insulin and escaping elimination of effector T cells.

Syfte och mål

Based on SRQ RA cohort, we study risk of type 2 diabetes in RA patientswith respect to gender and autoantibody production. We study if anti-rheumatic dtrugs increase the risk of T2D.

Based on the recently reported survivin-mediated insulin resistance in T cells, we want to study a connection between insulin and survivin levels in pre-RA and early RA patients. We want to investigate how anti-rheumatic drugs increase insulin sensitivity and reduce inflammation.

Metod

Selection period 2016-2022 will identify patients with RA diagnosis in SRQ. To each patient, five arthritis-free individuals will be identified among general population that match to RA patients by age, gender, and region of domicile. This material will be linked to National Patient register and Drug Prescription Register to identify cases of T2D.

We work with material of 900 1st visit patients with arthralgia and early RA,who are prospectively followed for 10y. In this material we apply serum levels of insulin and survivin and the intracellular survivin ito calculate the risk of RA and T2D development. We use gene transcription and methylation profile of sorted T cells for deep analysis of insulin pathways.

Betydelse för patienten

In this project we connect important clinical conditions insulin resistance and autoimmunity and study their role for (a) development of RA disease. We believe that survivin-dependent insulin resitance indicate a revertable phase of RA aiding disease prevention. (b) individual choice of drug. Effect of antirheumatic drugs on insulin resistance helps elimination of autoimmune cells. (c) prevention of comorbidities. Insulin resistance is one of the leading causis of early death. It should be recognized to improve health of RA patients.