Clinical and Genetic Spectrum of Pyrinopathies in Brazilian Patients: Insights from the First Year of the CNE3i National Cohort

Although Brazil has experienced substantial immigration from the Middle East and Italy, regions with a higher prevalence of pyrin-associated autoinflammatory diseases, pyrinopathies, remain under-investigated in the country. Through a national collaborative effort, the Centro Nacional de Erros Inatos da Imunidade e Imunodesregulação (CNE3i) has systematically collected data on pyrinopathies across Brazil since 2024. Here, we report the first-year dataset from CNE3i on pyrinopathies, highlighting their genetic diversity and clinical presentation within the Brazilian population. In this first-year report, we describe 47 individuals with pyrin-related diseases. Overall, 53% were female (n = 23), with a mean current age of 27 years (range 2–74). Most of them were from the state of São Paulo, and just one was a Syrian refugee. Consanguinity was documented in 4 families. Among the patients for whom clinical information was available, periodic fever was the most common finding, present in 96.3% (n = 26/27), with 73.3% (n = 11/15) experiencing more than five episodes per year. Additionally, mucocutaneous involvement was observed in 64.5% (n = 20/31), arthralgia in 61.4% (n = 14/17), lymphoid involvement in 34.5% (n = 10/29), and thoracic pain in 84.1% (n = 6/7). The top three MEFV variants identified were those located at positions 744 (n = 5), 694 (n = 5), and 369 (n = 4) of the protein. One-third (n = 13; 27%) harbored biallelic mutations, and three patients, all with adult-onset disease and most (n = 2) with AAA (AA amyloidosis), were genetically negative through genome sequencing. Half of the individuals achieved a complete clinical and laboratory response with colchicine (n = 28; 59%). Biologics (anti-TNF, anti-IL6, and anti-IL1) were required for 31% (n = 15), whereas AAA was found in 12% (n = 6). Just one patient with a kidney-related AAA had a completely satisfactory response to colchicine. The results are summarized in the supplementary table. The initial findings regarding MEFV-related autoinflammatory diseases (commonly referred to as pyrinopathies) reflect the complex ancestry of the Brazilian population, with the most frequently found variants associated with Jewish (p.694) and Arab, Turkish, and Cypriot (p.744) ancestries. Moreover, we also noted a slightly higher frequency of AAA (usually 8.6%), which may be a result of delays in diagnosis of epigenetic interactions for the MEFV gene in the Brazilian population, such as gastrointestinal microbiota. Tabular data are included as downloadable supplement files.