Tralokinumab Treatment in Adult Atopic Dermatitis Patients: 28-Week Evaluation of Clinical Effectiveness, Safety, Serum Proteins and Total IgE Levels.

Introduction And Objectives: Tralokinumab-a biological that specifically targets interleukin-13-is one of the newer advanced systemic treatments for patients with moderate-to-severe atopic dermatitis (AD). Although safety and efficacy have been shown in phase-III clinical trials, daily practice data are needed. Therefore, the aim of this study was to evaluate 28-week safety and effectiveness, serum proteins and total IgE levels in adult AD patients treated with tralokinumab in daily practice.

The 'T paradox' in inflammatory arthritis.

Classic regulatory T (T) cells expressing CD4 and the hallmark transcription factor FOXP3 are integral to the prevention of multi-system autoimmunity. However, immune-mediated arthritis is often associated with increased numbers of T cells in the inflamed joints. To understand these seemingly conflicting observations, which we collectively describe as 'the T paradox', we provide an overview of T cell biology with a focus on T cell heterogeneity, function and dysfunction in arthritis.

Type I interferon biomarker in idiopathic inflammatory myopathies: associations of Siglec-1 with disease activity and treatment response.

Objectives: Novel biomarkers are needed to guide therapy in idiopathic inflammatory myopathies (IIM). Expression of Siglec-1, a type I interferon biomarker, was examined in adult patients with IIM in relation to disease activity and treatment response.

Methods: We analysed PBMC samples from 19 newly diagnosed adult IIM patients who participated in a phase-2 pilot study on efficacy of intravenous immunoglobulin (IVIG) monotherapy, and from 9 healthy controls.

Human breastmilk memory T cells throughout lactation manifest activated tissue-oriented profile with prominent regulation.

Breastfeeding provides important immunological benefits to the neonate, but how the different immunoactive components in breastmilk contribute to immunity remains poorly understood. Here, we characterized human breastmilk T cells using single-cell RNA-Seq and flow cytometry. Breastmilk contained predominantly memory T cells, with expression of immune signaling genes, high proliferation, and an effector Th1/cytotoxic profile with high cytokine production capacities.

Multidimensional profiling of human T cells reveals high CD38 expression, marking recent thymic emigrants and age-related naive T cell remodeling.

Thymic involution is a key factor in human immune aging, leading to reduced thymic output and a decline in recent thymic emigrant (RTE) naive T cells in circulation. Currently, the precise definition of human RTEs and their corresponding cell surface markers lacks clarity. Analysis of single-cell RNA-seq/ATAC-seq data distinguished RTEs by the expression of SOX4, IKZF2, and TOX and CD38 protein, whereby surface CD38 expression universally identified CD8 and CD4 RTEs.

Personalised medicine in juvenile dermatomyositis: From novel insights in disease mechanisms to changes in clinical practice.

Juvenile dermatomyositis is characterized by childhood-onset chronic inflammation of the muscles and skin, with potential involvement of other organs. Patients are at risk for long-term morbidity due to insufficient disease control and steroid-related toxicity. Personalised treatment is challenged by a lack of validated tools that can reliably predict treatment response and monitor ongoing (subclinical) inflammation, and by a lack of evidence regarding the best choice of medication for individual patients.

Clinical and translational attributes of immune-related adverse events.

With immune checkpoint inhibitors (ICIs) becoming the mainstay of treatment for many cancers, managing their immune-related adverse events (irAEs) has become an important part of oncological care. This Review covers the clinical presentation of irAEs and crucial aspects of reversibility, fatality and long-term sequelae, with special attention to irAEs in specific patient populations, such as those with autoimmune diseases. In addition, the genetic basis of irAEs, along with cellular and humoral responses to ICI therapy, are discussed.

Ocular surface disease in moderate-to-severe atopic dermatitis patients and the effect of biological therapy.

Atopic dermatitis (AD) is a chronic inflammatory skin disease for which new targeted therapies are currently available. Due to the increased rates of ocular surface disease (OSD) reported during treatment with these new targeted treatments, more insight into the occurrence and pathomechanism of OSD in moderate-to-severe AD patients is needed. Therefore, this review's first part highlights that most patients with moderate-to-severe AD already have characteristics of OSD before starting targeted treatment.

Toxicity-specific peripheral blood T and B cell dynamics in anti-PD-1 and combined immune checkpoint inhibition.

Immune checkpoint inhibitors (ICI) have revolutionized the treatment landscape of advanced malignancies, but come with a diverse spectrum of immune-related adverse events (irAEs). Mechanistic studies can aid the transition from expert-opinion to evidence-based irAE treatment strategies. We aimed to longitudinally characterize peripheral blood T and B cell dynamics in ICI-treated patients by multicolor flow cytometry and serum multiplex immunoassay at baseline, ± 3 weeks and ± 6 weeks or upon clinically relevant irAEs.

Highly multiplexed spatial analysis identifies tissue-resident memory T cells as drivers of ulcerative and immune checkpoint inhibitor colitis.

Colitis is a prevalent adverse event associated with immune checkpoint inhibitor (ICI) therapy with similarities to inflammatory bowel disease. Incomplete mechanistic understanding of ICI colitis curtails evidence-based treatment. Given the often-overlooked connection between tissue architecture and mucosal immune cell function, we here applied imaging mass cytometry (IMC) to gain spatial proteomic insight in ICI colitis in comparison to ulcerative colitis (UC).

Compartment-driven imprinting of intestinal CD4 T cells in inflammatory bowel disease and homeostasis.

The mucosal immune system is implicated in the etiology and progression of inflammatory bowel diseases. The lamina propria and epithelium of the gut mucosa constitute two separate compartments, containing distinct T-cell populations. Human CD4 T-cell programming and regulation of lamina propria and epithelium CD4 T cells, especially during inflammation, remain incompletely understood.

Immunosuppression for immune-related adverse events during checkpoint inhibition: an intricate balance.

Immune checkpoint inhibitors (ICIs) have changed perspectives for patients with cancer, but come with severe immune-related adverse events (irAEs). To prevent fatality or chronicity, these irAEs are often promptly treated with high-dose immunosuppressants. Until recently, evidence on the effects of irAE management on ICI efficacy has been sparse.

Dupilumab-associated ocular surface disease in atopic dermatitis patients: Clinical characteristics, ophthalmic treatment response and conjunctival goblet cell analysis.

Background: Dupilumab-associated ocular surface disease (DAOSD) is frequently reported as side effect in atopic dermatitis (AD) patients. Therefore, the aim of this study was to investigate the frequency and severity of DAOSD, ophthalmic treatment response and to learn more about the effect of dupilumab on conjunctival goblet cells (GC).

Methods: This prospective study included dupilumab-treated AD patients between February 2020 and June 2022 from the University Medical Centre Utrecht.

Non-Infectious Uveitis Secondary to Dupilumab Treatment in Atopic Dermatitis Patients Shows a Pro-Inflammatory Molecular Profile.

Severe uveitis is a rare complication of interleukin-4 receptor alpha blocking by dupilumab in topic dermatitis (AD) patients. The aim of this study was to describe five moderate-to-severe AD patients who developed uveitis during dupilumab treatment and to compare the proteomic profile of aqueous humor (AqH) of dupilumab-associated uveitis (n=3/5 available samples) with non-infectious uveitis (n=27) and cataract controls (n=11). Included patients were treated at the University Medical Center Utrecht (the Netherlands).

Biomarkers in atopic dermatitis.

Atopic dermatitis (AD) is a complex and highly heterogeneous inflammatory skin disease. Given the highly heterogeneous character of AD, it is unlikely that every patient will respond equally to a particular treatment. The recent introduction of novel targeted therapies for AD has driven the need for patient stratification based on immunologic biomarkers.

High dupilumab levels in tear fluid of atopic dermatitis patients with moderate-to-severe ocular surface disease.

Background: The patho-mechanism of ocular surface disease (OSD) in dupilumab-treated atopic dermatitis (AD) patients remains unclear. The aim of this study is to measure dupilumab levels in tear fluid and serum, and relate these findings to the severity of OSD during dupilumab treatment in AD patients.

Methods: This prospective study included dupilumab-treated moderate-to-severe AD patients who were seen by a dermatologist and an ophthalmologist before the start of dupilumab (baseline), and after 4 and 28 weeks of dupilumab treatment.