Welcome to the ESID 2022 Meeting Interactive Programme
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Introduction
CIS Senior: HSCT in the US
CIS Junior: ALTERED STAT1 SIGNALLING YIELDS CD8+ T CELL DYSFUNCTION IN INBORN ERRORS OF IMMUNITY
Abstract
Background and Aims
Interferons are a group of cytokines known to play a pivotal role in mediating antiviral and inflammatory responses. STAT1 has a central role within this signaling axis, relaying inflammatory signals, and orchestrating the antiviral immune response, including a key role in CD8 T-cells (CD8T). There is currently limited understanding of how alterations in STAT1 signaling affect CD8T function in vivo in human cells. Here, we evaluate how modulating STAT1 signaling can affect CD8T function by studying patients with STAT1 loss of function (LOF) and gain of function (GOF).
Methods
To measure the mechanisms induced by alterations in STAT1 activity, we collected multimodal high-dimensional immune-profiling and immunometabolic functional data from >24 STAT1 GOF and several STAT1 LOF patients and age matched controls. >7 Aicardi-Goutières-Syndrome (AGS) patients were included a disease control for chronic interferon signaling.
Results
This cohort allows us to begin to differentiate the effects of interferon signaling vs isolated alterations in STAT1 activity on CD8T function. In all three groups we find a reduced capacity of CD8T to produce interferon-gamma upon stimulation. STAT1 GOF CD8T show up-regulations in activation markers such as CD38, while AGS CD8T additionally express Eomes and Tbet. In contrast STAT1 LOF CD8T up-regulate inhibitory receptors. Preliminary data further suggests that certain interferon stimulated genes correlate with the expression levels of these activation markers.
Conclusions
Thus, by studying these three groups we are gaining novel insights into the mechanisms by which altered STAT1 activity vs chronic interferon stimulation cause CD8T dysfunction.
ASID Senior: Update on African Guidelines and Registry
ASID Junior: SCID in Africa
LASID Senior: LASID Registry
LASID Junior: Antibody Responses to Vaccines in IEI
APSID Senior: HSCT in India
APSID Junior: AUTOIMMUNITY IN A LARGE COHORT OF INBORN ERRORS OF IMMUNITY! – EXPERIENCE FROM A TERTIARY CARE CENTER IN SOUTH INDIA
Abstract
Background and Aims
Autoimmunity can be the first clinical presentation or sequel of Inborn Errors of Immunity (IEI). Molecular genetics and next-generation sequencing technologies have increased our understanding of the complex relationships between IEI and autoimmune diseases.Aim: To study the profile of autoimmune manifestations in patients with IEI at a tertiary care center in Bangalore, India.
Methods
A retrospective review of clinical records of 241 patients with IEI was performed.They were categorized according to the International Union of Immunological Societies (IUIS), PID Committee Report on IEI (2019).Patients who had autoimmune manifestations at presentation or during the course of their illness were included in the study.
Results
The most common IEIs noted were Severe Combined Immune Deficiency (SCID) (38,15.7%) followed by phagocytic disorders and antibody deficiency diseases.A total of 67 autoimmune manifestations were noted in 55 (22.8%) patients. Male to female ratio in this subgroup was 2.5:1. Amongst them, autoimmunity was the key or only manifestation in 20 (8.2%) patients.The most common manifestation in our cohort was inflammatory colitis (29%) followed by autoimmune cytopenia (20%), autoimmune endocrinopathy (12.7%), and arthritis (12.7%). Inflammatory colitis was common among patients with phagocytic disorders. Pyoderma gangrenosum, systemic lupus erythematosus, and Kawasaki disease were also reported.Patients received immunosuppression in the form of steroids (n=36), azathioprine (n=5), cyclosporine (n=2),methotrexate (n=2), rituximab (n=3),sirolimus (n=1), adalimumab (n=1) and infliximab (n=1). The overall survival was 76% in the “autoimmune” cohort.
Conclusions
Autoimmunity is a frequent manifestation in patients with IEI. Managing autoimmunity in patients with IEI is a challenge, due to their inherent predisposition to infections.