Ana Carolina da Matta Ain

Chronic granulomatous disease (CGD) is an inborn error of immunity (IEI) caused by mutations in genes encoding components of the NADPH oxidase complex, leading to defective microbial killing and increased susceptibility to infections. This study analyzed clinical, genetic, and geospatial data from 238 CGD patients across eight Latin American countries. Genetic variants were identified in 141 patients (59%), with XL-CGD being the most common form (77%). Pneumonia (80%), lymphadenopathy (63%), and skin infections (55.5%) were frequent, with bacteria and fungi, such as Staphylococcus aureus, Aspergillus spp., and mycobacteria, as major pathogens. Antimicrobial prophylaxis was widely used, while IFN-γ was mainly prescribed in Mexico, mainly in cases of classic CGD (XL-CGD). Hematopoietic stem cell transplantation (HSCT) did not improve survival compared to prophylaxis. The leading cause of death was infection, particularly pneumonia and sepsis. XL-CGD patients had worse survival outcomes. The study highlights the need for improved genetic diagnosis, newborn screening, regional treatment guidelines, and expanded access to HSCT.

Severe combined immunodeficiency, SCID, is a pediatric emergency that represents the most critical group of inborn errors of immunity (IEI). Affected infants present with early onset life-threatening infections due to absent or non-functional T cells. Without early diagnosis and curative treatment, most die in early infancy. As most affected infants appear healthy at birth, newborn screening (NBS) is essential to identify and treat patients before the onset of symptoms. Here, we report 47 Brazilian patients investigated between 2009 and 2020 for SCID due to either a positive family history and/or clinical impression and low TRECs. Based on clinical presentation, laboratory finding, and genetic information, 24 patients were diagnosed as typical SCID, 14 as leaky SCID, and 6 as Omenn syndrome; 2 patients had non-SCID IEI, and 1 remained undefined. Disease onset median age was 2 months, but at the time of diagnosis and treatment, median ages were 6.5 and 11.5 months, respectively, revealing considerable delay which affected negatively treatment success. While overall survival was 51.1%, only 66.7% (30/45) lived long enough to undergo hematopoietic stem-cell transplantation, which was successful in 70% of cases. Forty-three of 47 (91.5%) patients underwent genetic testing, with a 65.1% success rate. Even though our patients did not come from the NBS programs, the diagnosis of SCID improved in Brazil during the pilot programs, likely due to improved medical education. However, we estimate that at least 80% of SCID cases are still missed. NBS-SCID started to be universally implemented in the city of São Paulo in May 2021, and it is our hope that other cities will follow, leading to early diagnosis and higher survival of SCID patients in Brazil.

We would like to report our experience in the deployment of an Immunology outpatient clinic that over 14 years became a Reference Center for Inborn Errors of Immunity (IEI) in Brazil, which is located in the city of Taubaté, in the region of Vale do Paraíba, state of São Paulo, responsible for serving a region of approximately 2.5 million inhabitants. During this period, we participated in the pilot project to implement neonatal screening for severe combined immunodeficiency and initiated courses for physicians from basic health units, implementation of classes on clinical immunology in the undergraduate program of medicine, implementation of an outpatient clinic at the city's Faculty of Medicine, in addition to the assessment of patients hospitalized in emergency and intensive care units. Thus, the implementation of a Reference Center for IEI in Latin America proved to be viable and can serve as a model for other services to be initiated. Based on our experience, we suggest some itens for additional IEI centers to emerge.