Yvonne Vercoulen, Netherlands

UMC Utrecht Center for Molecular Medicine

Presenter of 1 Presentation

Poster Display Immune dysregulation & autoimmunity

MULTIPARAMETER CHARACTERIZATION OF TISSUE INFLAMMATION IN PID PATIENTS WITH IMMUNE DYSREGULATION ELUCIDATES DIFFERENT UNDERLYING INFLAMMATORY RESPONSES

Lecture Time
10:53 - 10:54
Room
Poster Area
Date
19.09.2019, Thursday
Session Time
10:00 - 17:00
Board Number
127
Presentation Topic
Immune dysregulation & autoimmunity

Abstract

Background and Aims

Primary immunodeficiency (PID) are genetically inherited defects of the immune system that occur in approximately 1 in 2000 live births. PID patients are a heterogeneous group with increased risk of recurrent pathogenic infections and/or inflammatory disease. Inflammatory disease can be organ specific or systemic, and is caused by a dysregulated immune response. Patients suffering from immune dysregulation have increased morbidity and mortality, and often require specialized and urgent care. Due to the heterogeneity of the disorders it is impossible to develop a common treatment protocol, and current treatment usually reflects organ-specific immunosuppressant treatment used in other inflammatory diseases. To promote precision diagnosis, we aim to gain insight in the underlying inflammatory processes in the tissue in PID immune dysregulation.

Methods

We utilized an innovative and powerful multiparameter analysis method, imaging mass cytometry, to visualize the inflammatory response in tissue biopsies from 4 patients with immune dysregulation in the gut. Patients had either a PI3KR1, STAT1, or STAT3 variant.

Results

Inflamed intestinal and colon tissue biopsies showed metabolic activity through elevated phosphorylated-S6, as expected in inflamed tissue. However, we detected differences in the types of cells infiltrating the gut (CD8+ cytotoxic T cells, memory T cells), and in the local inflammatory cytokine responses (IL-17, IFNgamma, IL-10) between the different patients with immune dysregulation.

Conclusions

We show that tissue inflammation in patients with immune dysregulation in the gut is heterogeneous, which emphasizes that understanding the nature of tissue inflammation is vital for precision diagnosis and, consequently, targeted treatment for PID patients with inflammatory immune dysregulation.

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