Severe combined immunodeficiency articles from across Nature Portfolio

Fifteen years’ follow-up of clinical development and real-world data from 43 patients show that gammaretroviral gene therapy for adenosine deaminase deficiency has a positive long-term efficacy profile, warranting continued safety monitoring of patients receiving gene therapy.

Variants of concerns arise from SARS-CoV-2 mutations poise as severe public health threats. Here the authors chronicle SARS-CoV-2 mutations onset and immune parameters in an immunocompromised patient with continuous virus-shedding, thereby hinting potential intra-host viral evolution and escape facilitated by ineffective T cell immunity.

Kubo et al. report two kindreds that exhibit a deficiency of iRHOM2, which interacts with ADAM17, leading to defective release of TNF and CD62L and resulting in altered immune responses to opportunistic infections.

Hematopoietic stem-cell gene therapy has proven to be an effective treatment for several primary immunodeficiencies, and yet companies in this space are withdrawing from the EU market. Technological and regulatory innovations and a change to cost–benefit models are needed so that rare disease patients can receive these life-saving medicines.

A lentivirus-based treatment restores immune function with minimal side effects in children with adenosine deaminase deficiency.

A humanized mouse model of X-linked severe combined immunodeficiency suggests that the safety of correcting the human IL2RG gene in haematopoietic stem cells depends on both gene-correction frequency and the conditioning regimen used before cell transplantation.

A cohort of immunodeficient children lead near-normal lives after bone marrow transplantation, despite a profound deficiency of innate lymphoid cells (ILCs).