Inhibition of interleukin-1 with rilonacept is not effective in cold urticaria-Results of a randomized, placebo-controlled study.

Background: Cold urticaria (ColdU) is characterized by pruritic wheals following exposure of the skin to cold. Many patients show insufficient response to antihistamines, the first line treatment. Based on the high efficacy of interleukin-1(IL-1)-inhibition in cold-induced urticarial autoinflammatory diseases, we assessed the effects of rilonacept, an IL-1 inhibitor, in ColdU patients unresponsive to standard treatment.

Soluble IgE-binding factors in the serum of food-allergic patients: Possible pathophysiological role of soluble FcεRI as protective factor.

Background: IgE-mediated food allergy is the result of an aberrant immune response involving the interaction of a food allergen with its specific IgE bound to FcɛRI, the high affinity IgE receptor, on mast cells. Allergen-specific IgE also binds to soluble binding factors, but, their expression and role in food allergy is not well characterized. Here, we assess the prevalence and relevance of soluble IgE binding factors in food allergy and tolerance.

In Urticarial Vasculitis, Long Disease Duration, High Symptom Burden, and High Need for Therapy Are Linked to Low Patient-Reported Quality of Life.

Background: Urticarial vasculitis (UV) is a rare and difficult-to-treat chronic skin disease defined by long-lasting urticarial lesions and the histopathologic finding of leukocytoclastic vasculitis. As of yet, little is known about UV patients' perspective on the disease.

Objective: To assess UV patients' perspective on the clinical course, treatment response, greatest challenges, and quality-of-life (QOL) impairment.

Simultaneous Genetic Ablation of PD-1, LAG-3, and TIM-3 in CD8 T Cells Delays Tumor Growth and Improves Survival Outcome.

Immune checkpoint inhibitors (ICI) represented a step forward in improving the outcome of patients with various refractory solid tumors and several therapeutic regimens incorporating ICI have already been approved for a variety of tumor entities. However, besides remarkable long-term responses, checkpoint inhibition can trigger severe immune-related adverse events in some patients. In order to improve safety of ICI as well as T cell therapy, we tested the feasibility of combining T cell-based immunotherapy with genetic disruption of checkpoint molecule expression.

Characterization of the effects on pruritus by novel treatments for atopic dermatitis.

Chronic pruritus is a common and debilitating symptom in patients with atopic dermatitis and contributes to impairment of quality of life. Effective treatment of pruritus should therefore be one of the main treatment goals in patients with atopic dermatitis. Pathophysiologically, the histamine-independent pruritogens interleukin-31, interleukin-13, and interleukin-4, have been shown to play a major role in atopic dermatitis.

Spectrum of Genetic Autoinflammatory Diseases Presenting with Cutaneous Symptoms.

Autoinflammatory diseases comprise a group of chronic disabling entities characterized by inflammation without the presence of infectious agents, auto-antibodies or antigen-specific T-cells. Many autoinflammatory diseases are caused by monogenic defects, which lead to disturbed immune signalling with release of proinflammatory mediators. In addition to interleukin-1β and interleukin-18, interferons play a key role in the pathophysiology of these disorders.

Generation and validation of murine monoclonal and camelid recombinant single domain antibodies specific for human pancreatic glycoprotein 2.

Pancreatic secretory zymogen-granule membrane glycoprotein 2 (GP2) has been identified as a major autoantigenic target in Crohn's disease patients. It was reported recently that a long (GP2a) and a short (GP2b) isoform of GP2 exist and that in the outcome of inflammatory bowel diseases (IBD) GP2-specific autoantibodies probably appear as new serological markers for diagnosis and therapeutic monitoring. To investigate this further and in order to establish diagnostic tools for the discrimination of both GP2 isoforms, a set of different murine monoclonal and camelid recombinant single domain antibodies (camelid VHH) was generated and validated in various enzyme-linked immunosorbent assay (ELISA) formats, immunofluorescence on transgenic cell lines and immunohistochemistry on monkey pancreas tissue sections.

Generation of murine monoclonal antibodies with specificity against conventional camelid IgG1 and heavy-chain only IgG2/3.

Camelids possess antibodies with a conventional four-chain structure consisting of two heavy and two light chains (of subclass IgG1) but further they also generate heavy-chain only antibodies (of subclass IgG2 and 3) which are fully functional in antigen binding. In this study subclass-specific murine monoclonal antibodies specific to conventional camelid IgG1 and heavy-chain only IgG2/3 were generated and validated for the use as potent secondary detection reagents. The monoclonal antibodies are able to differentiate between all camelid IgGs, conventional four-chain camelid antibodies (of subclass IgG1) and exclusively heavy chain-only antibodies (of subclasses IgG2 and IgG3).