Severe combined immunodeficiency articles from across Nature Portfolio

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.

Individuals with SYK gain-of-function variants develop immunodeficiency and systemic inflammation, which are recapitulated in a knock-in mouse model. Treatment of these mice with bone marrow transplantation or with a SYK inhibitor ameliorates disease symptoms, highlighting potential therapeutic strategies for patients with SYK mutations.