Food Allergy: What We Know Now.

Food allergy is an adverse immune reaction that occurs reproducibly on exposure to a given food. Prevalence rates of food allergy continue to increase worldwide, sparking continual research efforts in finding a suitable and safe cure. Food avoidance, the current standard of care, can be difficult to achieve. This review aims to provide a broad overview of immunoglobulin E-mediated food allergy, highlighting its epidemiology, masqueraders, immunopathophysiology, clinical presentation, diagnostic work-up and available preventative and treatment strategies. This review also discusses novel, investigative therapies that offer promising therapeutic options, yet require continued research efforts to determine safety effects. Inducing tolerance, whether by immunotherapy or by the administration of monoclonal antibodies, allows us to move toward a cure for food allergy, which could vastly change this field of allergic diseases in the coming decades.

Rapid molecular diagnostics of severe primary immunodeficiency determined by using targeted next-generation sequencing.

BACKGROUND: Primary immunodeficiency diseases (PIDDs) are inherited disorders of the immune system. The most severe form, severe combined immunodeficiency (SCID), presents with profound deficiencies of T cells, B cells, or both at birth. If not treated promptly, affected patients usually do not live beyond infancy because of infections. Genetic heterogeneity of SCID frequently delays the diagnosis; a specific diagnosis is crucial for life-saving treatment and optimal management. OBJECTIVE: We developed a next-generation sequencing (NGS)-based multigene-targeted panel for SCID and other severe PIDDs requiring rapid therapeutic actions in a clinical laboratory setting. METHODS: The target gene capture/NGS assay provides an average read depth of approximately 1000×. The deep coverage facilitates simultaneous detection of single nucleotide variants and exonic copy number variants in one comprehensive assessment. Exons with insufficient coverage (<20× read depth) or high sequence homology (pseudogenes) are complemented by amplicon-based sequencing with specific primers to ensure 100% coverage of all targeted regions. RESULTS: Analysis of 20 patient samples with low T-cell receptor excision circle numbers on newborn screening or a positive family history or clinical suspicion of SCID or other severe PIDD identified deleterious mutations in 14 of them. Identified pathogenic variants included both single nucleotide variants and exonic copy number variants, such as hemizygous nonsense, frameshift, and missense changes in IL2RG; compound heterozygous changes in ATM, RAG1, and CIITA; homozygous changes in DCLRE1C and IL7R; and a heterozygous nonsense mutation in CHD7. CONCLUSION: High-throughput deep sequencing analysis with complete clinical validation greatly increases the diagnostic yield of severe primary immunodeficiency. Establishing a molecular diagnosis enables early immune reconstitution through prompt therapeutic intervention and guides management for improved long-term quality of life.

Recognition, treatment, and prevention of anaphylaxis.

Anaphylaxis is an acute and potentially lethal multisystem allergic reaction that occurs in a variety of clinical scenarios and is almost unavoidable. Immunologic reactions to medications, foods, and insect stings cause most episodes, but virtually any substance capable of inducing systemic degranulation of mast cells and basophils can produce anaphylaxis. All health care professionals must be able to recognize anaphylaxis promptly, be prepared to treat it appropriately, and be able to provide preventive recommendations. Similarly, at-risk individuals must be prepared to self-treat anaphylaxis promptly if prevention fails.