Innovations in Care of Inborn Errors of Immunity in Brazil: CNE3I, the Brazilian National Center for Inborn Errors of Immunity and Immune Dysregulation Diseases

Inborn errors of immunity (IEI), once considered rare, are more common than previously thought, affecting up to 1:1000 individuals, with 555 IEI identified involving variants in 546 genes. This expanded genetic and clinical understanding underscores the need for early detection and national centers to address diagnostic disparities and improve management. In this context, the Centro Nacional de Erros Inatos da Imunidade e Imunodesregulação (CNE3i) (Financiadora de Estudos e Projetos [FINEP] funded 0956/24) was established at Hospital das Clínicas of the Faculty of Medicine of the University of São Paulo (HCFMUSP) in 2024 as a genetic hub for linked centers collaborating with CoBEII (n = 63), historically supported by the Jeffrey Modell Foundation. The project has enhanced HCFMUSP’s facilities, offering remote clinical assistance, genetic sequencing and validation, and the translational application of findings (Certificate of Presentation for Ethical Consideration [CAAE]: 73174223.1.1001.0068). Within a year, 56% of the target population (1,700 individuals) was included. A clinical registry, collecting 392 variables over ten years, confirmed the complex traits of IEI in 573 individuals. Telemedicine has prevented so far 126 lost workdays and 36 school absences, while saving 25.6 tons of CO2. An artificial intelligence platform (EMEDGENE Illumina) supported the prioritization of rare variants. The project has already analyzed 320 sequencing, identifying at least one candidate variant in 50% of cases. Autoinflammatory diseases accounted for 35% of samples, with the MEFV gene most frequently prioritized. A notable finding was the IL1RN deletion (p.Asp72_Ile76del) acting as a founder effect for deficiency of IL-1receptor antagonist (DIRA) (n = 8) in Brazil. CoBEII also promoted health equity in Brazil by conducting an educational program on clinical advances across various regions. These innovative efforts have had a positive educational and socioeconomical impact on IEI care in Brazil, a populous nation of 213 million. The project’s initial results highlight its ability to overcome racial biases, as Brazil is a trihybrid (Indian, African, and European ancestries) population, offering insights applicable to IEI diagnosis and research globally. Overall, the innovations introduced by CNE3I have significantly enhanced the care of IEI in Brazil, demonstrating that comprehensive genetic analysis and coordinated care can address longstanding disparities and improve outcomes for individuals with these conditions. The data are summarized in Figure 1.Figure 1.CNE3i Year 1. Main results obtained in the first year of CNE3i (Centro Nacional de Erros Inatos da Imunidade e Imunodesregulação) in Brazil. The CNE3i is a collaborative effort of Brazilian Reference Centers for Inborn Errors of Immunity established through CoBEII, creating a technopole for innovations in the care of IEI in Brazil, located at the University of São Paulo. On the left, the drops on the Brazilian map represent reference centers, with colors indicating the number of samples included per state. On the right side, the summarized results include: i) telemedicine, ii) sequencing and analysis, iii) clinical registry, and iv) medical education and disease awareness.