Treatment of psoriasis during pregnancy, an immunological puzzle and a delicate balance
Grantee: Renate van der Molen, Assistant Professor, Radboud University Medical Center
Amount: DKK 2,596,390
Grant category: Research Grants in open competition
Year: 2023
Geography: Netherlands
Renate van der Molen’s project will study the effect of psoriasis and the associated treatment with biologics on the pre-pregnancy uterine immune environment and also investigate the effect on trophoblast invasion using a co-culture cellular model.
Pregnancy in patients with immune-mediated diseases like psoriasis is challenging and requires a tightly regulated immune system. The mother’s immune system must prevent rejection of the fetus that partly represents paternal characteristics and thus foreign to the mother’s immune system, while still being alert to infections threatening herself and the baby. Additionally, the immune system is important for invasion of fetal cells (trophoblast cells), into the cell lining of the womb to form a healthy placenta. Thus, a dysregulated immune system, i.e., during flares of psoriasis, can negatively affect pregnancy.
Furthermore, knowledge of the effect of biologics to treat psoriasis, anti-TNFα, anti-interleukin-17 (IL17) and anti-IL23, on pregnancy is sparse. This complicates decision making on treatment of women with psoriasis before and during pregnancy.
In this project, Renate van der Molen and her team will therefore study the effect of psoriasis and the treatment with biologics on the local uterine immune environment. In addition, using an innovative in vitro co-culture model of trophoblasts and immune cells they will study the effect of psoriasis and the treatment with anti-TNFα, anti-IL17 or anti-IL23 on trophoblast invasion.
Renate van der Molen’s project will give insights to whether and how psoriasis and the treatment with biologics can affect a future pregnancy, which is a step towards better evidence based clinical decisions on the best treatment for women with psoriasis with a child wish.
Non-Tuberculous Mycobacterial Skin and Soft Tissue Infections: Using a Site-of-Disease Approach to Understand Pathophysiology and Improve Outcome
Grantee: Arjan van Laarhoven, PhD, Radboud University Medical Center
Amount: DKK 3,987,136
Grant category: Research Grants in open competition
Year: 2023
Geography: Netherlands
Arjan van Laarhoven’s project aims to improve the treatment of patients infected with mycobacteria by looking at the patient’s individual immune responses to the infection and combining this with optimized treatment with antibiotics.
Non-tuberculous mycobacteria (NTM) can cause debilitating skin and soft tissue infections (SSTI). NTM SSTI incidence rises with an aged population and increased use of immunosuppression. These infections require treatment with multiple antibiotics for minimally 4-6 months. Still, non-response or worsening of skin lesions occurs frequently, because antibiotics fail or too much inflammation occurs.
Arjan van Laarhoven and his team hypothesize that differences in the patients’ immune systems, so-called ‘patient endotypes’, drive these diverging treatment courses. Currently, the involved immune processes in the skin are not identified for NTM SSTI. In addition, it is unknown what antibiotic concentrations in the skin are needed to kill the NTM.
In this study, the team will investigate the individual immune response in the skin of NTM SSTI patients by measuring the activity of genes in individual cells, and how these cells interact. They will compare this to the immune cells in the patients’ blood and will use the combined information to understand how patients differ in their immune response to the infection. These findings will be related to the clinical response to antibiotic treatment.
After eight weeks of antibiotic treatment, a second biopsy will be taken, in which measurement of the number of live mycobacteria and the local skin drug concentrations of azithromycin and clofazimine will be repeated.
By providing targets for optimizing treatment with both antibiotics and anti-inflammatory or immunostimulating drugs, this project aims to improve the outlook for NTM SSTI patients.