Histamine is a bioactive amine which is considered a key player in the allergic response. Thus, histamine receptor blockers (antihistamines) play an important role in the treatment of a number atopic diseases such as allergic rhinitis, conjunctivitis, and acute and chronic forms of urticaria. Histamine is produced by immune cells but also by bacteria in the gut. Beyond its role in the acute allergic response, histamine exerts numerous effects by binding to its 4 pleiotropic G-protein coupled histamine receptors. Here, we describe the roles of these histamine receptors and antihistamines in the human system, clinical applications, side effects, and novel concepts for the usage of antihistamines with different specificity based on guidelines and recommendations.Statement of novelty: This review provides an overview of histamine receptors and links it to clinical relevance of antagonizing their action in clinical routine.

Introduction: Coronin 1A is part of a family of highly conserved actin regulatory proteins with key roles in T cell homeostasis and T cell receptor signaling. Null mutations in coronin 1A result in severe combined immunodeficiency, whereas hypomorphic mutations have been associated with a somewhat milder immunological phenotype. Nevertheless, all patients described so far have markedly reduced naïve peripheral T cells, impaired T cell responses to mitogens, and limited T cell receptor diversity. Interestingly, despite poor thymic output, thymus architecture appears normal. To date, only 2 cases of hematopoietic stem cell transplantation (HSCT) have been reported in coronin 1A deficiency.Aim: To describe the identification, transplantation course, and long term outcome of a Canadian Inuit patient diagnosed with coronin 1A deficiency.Methods: Patient chart review was performed in accordance with institutional research ethics approval. A combination of immunological investigations and molecular genetic analyses were utilized to identify a novel mutation in the tryptophan-aspartate repeat region of coronin 1A. Based on the patient’s profound T cell dysfunction, the decision was made to proceed with HSCT.Results: The patient presented with a history of recurrent urinary tract infections, otitis media, and developmental delay involving poor axial and peripheral muscle tone. Axillary lymphadenopathy was noted and subsequent thymus biopsy revealed aberrant CD7+ T cell deficiency. Lymphocyte responses to mitogens and T cell receptor excision circle levels were markedly reduced, consistent with the diagnosis of severe combined immunodeficiency. Whole exome sequencing and Sanger confirmation revealed a novel mutation in coronin 1A. HSCT using a HLA-matched unrelated donor resulted in long term engraftment and solid immune reconstitution.Conclusion: Very few patients with coronin 1A deficiency have been described to date, making it difficult to evaluate its natural history and management. Here, we describe the presentation, identification, transplantation, and outcome in our patient.Statement of novelty: We describe the successful hematopoietic stem cell transplantation course and outcome in a patient with a novel mutation in coronin 1A.

Background: The nuclear factor κ-light-chain enhancer of activated B cells (NF-κB) signaling pathway is a critical regulator of many important adaptive and innate immune responses. The NF-κB transcription factor family consists of 5 structurally related core proteins, one of which is NFKB1. Mutations in the NFKB1 gene has been reported in patients with common variable immune deficiency (CVID) as well as with a large spectrum of clinical features including recurrent viral, bacterial, and fungal infections, autoimmunity, inflammation, and malignancy.Aim: We describe the clinical characteristics of a pediatric patient with a novel mutation in NFKB1.Methods: Patient informed consent was obtained in accordance with approved protocols from the Research Ethics Board at the Hospital for Sick Children. Gene panel testing was employed to identify the immune aberration.Results: Our patient, a previously well 18-month-old boy of Philippines descent, presented with multi-lineage cytopenias (thrombocytopenia, hemolytic anemia, neutropenia), splenomegaly, and lymphadenopathy. He did not have prior history of recurrent infections. Immunological work-up showed normal numbers of T and B cells, normal quantitative immunoglobulins, and adequate vaccination titres. Gene panel testing revealed a novel heterozygous missense variant c.425T>C (p. Ile142Thr) in the NFKB1 gene. Due to persistent cytopenias unresponsive to steroids and IVIG, he was started on Sirolimus with improvement in symptoms.Conclusion: NFKB1 encodes for p105, which is processed to generate the active p50 transcription factor that can interact with different proteins to activate or inhibit downstream signaling. Our patient was found to have a missense mutation in the Rel homology domain (RHD) of p50, which has distinct functions including DNA binding, protein dimerization, and inhibitory protein binding. The clinical presentation described here broadens the scope of characteristics associated with heterozygous NFKB1 mutations.Statement of novelty: We report a novel heterozygous missense variant c.425T>C (p. Ile142Thr) in the NFKB1 gene in a pediatric patient with cytopenias, lymphadenopathy, and splenomegaly. To the best of our knowledge, this variant has not been previously reported.

This protocol is excerpted from recent clinical trials used to study the pharmacokinetics, safety, and tolerability of subcutaneously administered immunoglobulin (SCIG) in subjects with primary immunodeficiency. The primary objective is to determine the weekly dose of SCIG product that produces a steady-state area under the concentration-time curve of total immunoglobulin G level that is non-inferior to that of regularly administered intravenous immunoglobulin (IVIG). We include details of the target population, eligibility criteria, treatment phases, key assessments and procedures, and study analyses. Given that IVIG may be problematic in patients with poor venous access or those who develop systemic adverse effects, among others, the development of SCIG for use in the home setting provides an alternative treatment technique for adults and children with primary immunodeficiency.Statement of novelty: This protocol describes the main topics found in prospective clinical studies evaluating the safety and pharmacokinetics of SCIG in subjects with primary immunodeficiency.