Hemorrhage detected on imaging may predict poor outcomes in acute necrotizing encephalopathy associated with COVID-19. RANBP2 mutations have been identified in some cases, suggesting a genetic contribution to disease susceptibility and highlighting the need for further research.

X-linked MCTS1 deficiency causes susceptibility to mycobacterial disease. Four new patients carried three previously undescribed truncating or loss-of-expression variants, presenting with BCG disease or M. abscessus infection. Functional testing showed complete or partial loss of MCTS1 activity, expanding the clinical and genetic spectrum of this disorder.

Here, Jensen and colleagues studied type I interferon (IFN-I) neutralizing autoAbs in people with HIV, and found that the prevalence does not significantly differ from that in the general population. While hepatitic C and IFN therapy likely contribute to the development of IFN-I autoAbs, these may predispose to mucocutaneous herpesvirus infections and HPV-related neoplasia.

Cook et al. report a novel de novo heterozygous N236K mutation in PSTPIP1, identified in a patient with neonatal-onset PAMI that was ultimately fatal. The N236K mutation showed increased binding to pyrin and enhanced inflammasome formation. The authors also identify blood transcriptome changes in PAMI patients with both N236K and the more common E250K mutation.

We report vasculitis and interstitial lung disease in two siblings with a novel C1QB pathogenic variant. Patients responded to rituximab + tacrolimus or baricitinib. This report broadens the genotypic and phenotypic landscape of C1Q deficiency and extends on the similarities with other type 1 interferonopathies.

Inflammatory complications occur in many subjects with common variable immunodeficiency. We show that microbial bacterial 16S ribosomal DNA, significantly increased in the serum of these subjects, is associated with loss of IgA, leading to excess IFN-γ and increased serum B cell–activating factor (BAFF), both of which promote autoimmunity and inflammation.

Groen et al. identify neutralizing interferon-λ2/3 autoantibodies in 11.8% of individuals with cystic fibrosis, a greater than 10-fold higher prevalence than in control individuals. Autoantibody-containing plasmas enhanced respiratory virus replication in vitro, and associated with allergic rhinitis in patients, suggesting that interferon-λ2/3 autoantibodies have the potential to impact mucosal pathology.