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Background: Despite advances in the treatment of chronic urticaria, in a significant percentage of the patients symptoms are not fully controlled with conventional approaches. New strategies under development include blocking intracellular mediators of mast cell and basophil activation. Objective: We aim to investigate the effects of the Bruton's tyrosine kinase (BTK) inhibitor remibrutinib on human blood basophils and CD34+‐derived mast cells activation induced by serum obtained from chronic urticaria patients. Methods: Twenty‐two patients with chronic spontaneous urticaria (mean age 52 years, 27% women) and 22 patients with chronic inducible urticaria (46 years, 27% women) were included in the study together with a sex‐matched control group. Patients were classified as responders or non‐responders to anti‐IgE therapy on the basis of their clinical data, FcεR1a expression on blood basophils and total IgE levels. Changes on CD63 expression—as an activation marker‐, were used to evaluate in vitro the response of basophils and mast cells to serum exposure and the inhibitory effects of remibrutinib. Results: Remibrutinib inhibits degranulation induced by IgE cross‐linking in mast cells and basophils and also the activation triggered by factors present in the sera of spontaneous and inducible chronic urticaria patients. Patient's serum induces a greater degranulation of effector cells than controls. Activation of mast cells and basophils by patient sera and remibrutinib effects were not related to omalizumab responsiveness. Conclusion: Remibrutinib inhibits activation of human basophils and mast cells induced in vitro by exposure to the serum of chronic urticaria patients independently of their response to omalizumab. [ABSTRACT FROM AUTHOR]

The aim of the study was to assess drug levels, immunogenicity and sacroiliitis on MRI in patients with axial spondyloarthritis under biologic tapering strategy. Consecutive patients with axial spondyloarthritis who remained in low disease activity more than 1 year after dose tapering of infliximab and adalimumab were included. Plasma drug concentrations of TNF inhibitors and anti-drug antibodies were determined, and MRI of sacroiliac joints was evaluated. Of twenty patients included, eighteen had therapeutic drug levels, no patient had anti-drug antibodies, and no patient had active sacroiliitis on MRI. These data could support the biologic tapering strategy and their maintenance over time. [ABSTRACT FROM AUTHOR]

Antibodies to SARS-CoV-2 in patients with primary immunodeficiencies treated with nonspecific immunoglobulins N-reactive antibodies are readily increased upon infection [5] and, in convalescent patients, occasionally may even dominate the response [6].We reasoned that if these patients had recently become infected, they should have a prominent cellular response (mediated by T lymphocytes) against different viral antigens. However, when we studied the CD4 SP + sp and CD8 SP + sp T cell-mediated responses against epitopes from SARS-CoV-2 S1 and S2 subunits, we could not detect interferon gamma production in any of the patients ruling out a recent infection as a source of the antibodies. [Extracted from the article]

Background: IgE and high‐affinity IgE receptor (FcεRI) expression on basophils have been scarcely explored in patients with chronic inducible urticaria (CIndU). Objectives: To investigate baseline serum IgE and FcεRI expression on blood basophils in a large cohort of CIndU patients and its relationship to treatment response. Methods: Baseline total serum IgE and basophil FcεRI expression measured by flow cytometry in 165 patients with CIndU was studied. The relationship of both parameters with the response to antihistamine and anti‐IgE (omalizumab) treatment was considered in a subsample of CIndU patients. FcεRI expression in basophils was assessed by mean fluorescence intensity (MFI) and basophil FcεRI standardized density (receptors/cell). Results: The median FcεRI expression standardized per density in blood basophils was found significantly higher in patients with CIndU compared to HCs. A positive correlation was found between IgE serum levels and basophil FcεRI expression. Basal FcεRI expression was not related to antihistamine treatment response. However, it was related to omalizumab, and patients responding to omalizumab showed higher basal basophil expression of FcεRI levels. Non‐responders to the antihistamine showed significantly higher IgE serum levels. Conclusions: FcεRI receptor overexpression in patients with CIndU shows almost the same pattern than chronic spontaneous urticaria. It seems to be independent of CIndU subtypes. Although additional studies would be welcome, our work highlights the relevance of FcεRI receptor regulation in CIndU supporting autoimmune basophil and mast cell activation and may be a biomarker for response to anti‐IgE therapy. [ABSTRACT FROM AUTHOR]

Purpose: Use of adoptive immunotherapy with virus-specific T cells (VST) in patients with inborn errors of immunity prior to hematopoietic stem cell transplantation (HSCT) has been reported in few patients. We report our experience, reviewing all the cases previously reported. Methods: We report four children with inborn errors of immunity who received VST infusion in a pre-HSCT setting in two reference centers in Spain and review all inborn errors of immunity cases previously reported. Results: Taking into account our four cases, nine children have been reported to receive VST prior to HSCT to date: 3 severe combined immunodeficiency, 2 CTPS1 deficiency, 1 dyskeratosis congenital, 1 ORAI1 deficiency, 1 Rothmund-Thomson syndrome, and 1 combined immunodeficiency without confirmed genetic defect. In four patients, immunotherapy resulted in clinical improvement, allowing to proceed to HSCT. In these cases, the infusion was started closely to viral diagnosis [mean time 28 days (IQR; 17–52 days)], and the VST was followed shortly thereafter by HSCT [mean time 28 days (IQR; 10–99 days)]. Viremia was controlled after HSCT in two cases (performed 7 and 36 days after the infusion). Multiple infusions were required in many cases. Five out of nine patients died before receiving HSCT. These patients presented with a prolonged and uncontrolled infection before VST administration [mean time from viral diagnosis to VST infusion was 176 days (IQR; 54–1687)]. Conclusions: In patients with inborn errors of immunity, the efficacy of VST for treating disseminated viral infections in pre-transplant settings seems to have a limited efficacy. However, this therapy could be used in a pre-emptive setting before severe viral disease occurs or closely to HSCT. [ABSTRACT FROM AUTHOR]

Cytomegalovirus encephalitis is a challenging life‐threatening complication following hematopoietic stem cell transplantation for which medical treatment is usually ineffective or toxic. However, in recent years, adoptive T‐cell therapy has been reported to provide a significant chance of cure for patients with viral infections. Herein, two cases of pediatric patients successfully treated with third‐party donor‐derived virus‐specific T cells for CMV meningoencephalitis are reported. [ABSTRACT FROM AUTHOR]

Experimental autoimmune encephalomyelitis (EAE) constitutes a paradigm of antigen (Ag)-specific T cell driven autoimmune diseases. In this study, we transferred bone marrow cells (BMCs) expressing an autoantigen (autoAg), the peptide 40–55 of the myelin oligodendrocytic glycoprotein (MOG40–55), to induce preventive and therapeutic immune tolerance in a murine EAE model. Transfer of BMC expressing MOG40–55 (IiMOG-BMC) into partially myeloablated mice resulted in molecular chimerism and in robust protection from the experimental disease. In addition, in mice with established EAE, transfer of transduced BMC with or without partial myeloablation reduced the clinical and histopathological severity of the disease. In these experiments, improvement was observed even in the absence of engraftment of the transduced hematopoietic cells, probably rejected due to the previous immunization with the autoAg. Splenocytes from mice transplanted with IiMOG-BMC produced significantly higher amounts of interleukin (IL)-5 and IL-10 upon autoAg challenge than those of control animals, suggesting the participation of regulatory cells. Altogether, these results suggest that different tolerogenic mechanisms may be mediating the preventive and the therapeutic effects. In conclusion, this study demonstrates that a cell therapy using BMC expressing an autoAg can induce Ag-specific tolerance and ameliorate established EAE even in a nonmyeloablative setting.Molecular Therapy (2009) 17 5, 897–905 doi:10.1038/mt.2009.42 [ABSTRACT FROM AUTHOR]