Supervisor View Full Details 2nd

• infectious disease and the immune system

• Medicine

• Immunology
• Other

Allergy, Diagnostic Laboratory Immunology

The following projects are ongoing in our group
1. Clinical trials - Leniosilib in APDS (Phase 2), Icatibant Outcome Survey - Hereditary Angioedema, HyQviaPass - facilitated subcutaneous Immunoglobulin replacement in primary and secondary immunodeficiency
2. Investigator led studies - Attention Based Training as an Add on Treatment in Chronic Spontaneous Urticaria
3. Observational U-CARE projects - CURE registry, Chronic urticaria in Pregnancy, CSU+; collaboration with European UCARE network
4. Sex as a biological variable in allergic diseases
5. Differential inflammatory effects of modalities of immunoglobulin replacement therapy in antibody deficiency - does method matter?

Differential inflammatory effects of modalities of immunoglobulin replacement therapy in antibody deficiency - does method matter?
Common variable immunodeficiency (CVID), the most common primary immunodeficiency seen in clinical practice, represents a heterogeneous group of syndromes characterised serologically by low antibody levels and clinically by recurrent respiratory tract infections, granulomatous inflammation and autoimmunity. The choice of IRT administration modalities includes subcutaneous (SC), facilitated subcutaneous (fSC) and intravenous (IV) routes. The different routes are thought to be equivalent in their therapeutic effects. However, there are clear pharmacokinetic differences between the delivery methods. It is unclear whether these differences have a clinically relevant impact on inflammation. This is an important issue as such differences might have an impact on administration modality. We will investigate the effects on systemic inflammation and immune activation of different modalities of Immunoglobulin Replacement Therapy in Common Variable Immune Deficiency.

This pilot study will examine inflammatory indices in clinically stable patients with CVID at various time points during on each of the three different infusion modalities (n=5 in each group). Samples from a fourth cohort of treatment naïve patients commencing immunoglobulin replacement will also be collected (IVIG or fSCIG).

Baseline clinical data will be collected from all patients. Symptoms related to infusion will be assessed and patient reports of wellbeing measured along with Quality of Life. Analysed parameters will include numbers of circulating B and T cells will be recorded. Analysis of surface markers including CD45, CD19, CD21, CD24, IgD, CD4, CD8, TLR-4, HLA-DR and CD38 will be performed. Interleukin-8 (IL-8), interleukin-1β (IL-1β), interleukin-6 (IL-6), interleukin-10 (IL-10), tumor necrosis factor (TNF), and interleukin-12p70 (IL-12p70) protein levels will be measured using a bead based multiplex assay. Single cell RNA sequencing of circulating monocytes and CD4 positive T cells will be carried out to determine changes in expression at the different time points. This novel approach has the potential to highlight important and clinically relevant changes in cells related to immunoglobulin replacement.