A significant number of contributions to our understanding of primary immunodeficiencies in pathogenesis, diagnosis and treatment were published in the Journal in 2013. For example, deficiency of mast cell degranulation due to STAT3 deficiency was demonstrated to contribute to the difference on frequency of severe allergic reactions in AD-HIES patients, compared to atopic individuals with similar high IgE serum levels. High levels of non-glycosylated IgA were found in WAS patients and these abnormal antibodies might contribute to nephropathy in WAS. New described genes causing immunodeficiency included caspase recruitment domain 11 (CARD11), mucosa-associated lymphoid tissue 1 (MALT1) for combined immunodeficiencies, and tetratricopeptide repeat domain 7A (TTC7A) for mutations associated to multiple atresia with combined immunodeficiency. Other observations expand the spectrum of clinical presentation of specific genes. (e.g., adult onset idiopathic T-cell lymphopenia and early onset autoimmunity might be due to hypomorphic mutations of the RAG genes). Newborn screening in California established incidence of SCID at 1/66,250 live births. The use of HSCT for primary immunodeficiencies was reviewed, with recommendations to give priority to research oriented to establish best regimens to improve safety and efficacy of bone marrow transplantation. These represent only a fraction of significant research done in primary immunodeficiencies that has accelerated the quality of care of these patients. Genetic analysis of patients has demonstrated multiple phenotypic expressions of immune deficiency in patients with nearly identical genotypes, suggesting that additional genetic factors, possibly gene dosage, or environmental factors are responsible for this diversity.