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. 2022 Nov;42(8):1708-1720.
doi: 10.1007/s10875-022-01302-9. Epub 2022 Jul 30.

Inborn Errors of Immunity in Patients with Adverse Events Following BCG Vaccination in Brazil

Paula T Lyra  1   2 , Edvaldo Souza  3   4 , Ana Carla A Moura  3   5 , Marina C Matta  6 , Leuridan C Torres  6 , Antonio Victor Campos Coelho  7 , Maria Ângela W Rocha  5 , Luiz Arraes  3   8 , João Bosco Oliveira  7
Affiliations

Inborn Errors of Immunity in Patients with Adverse Events Following BCG Vaccination in Brazil

Paula T Lyra et al. J Clin Immunol. 2022 Nov.

Abstract

Objective: The Bacille Calmette-Guérin (BCG) vaccine is routinely applied in Brazil. Adverse events (AE) may occur in patients with inborn or acquired immunodeficiencies, varying between local (BCGitis) or disseminated (BCGosis) reactions. We evaluated 53 individuals with local or disseminated adverse events to BCG vaccination to assess if they had inborn errors of immunity (IEI).

Methods: Patients diagnosed with an adverse event following BCG vaccination between 2014 and 2017 were included in the study. We collected clinical data, immunophenotyped T and B lymphocytes, and natural killer cells (NK), assessed oxidative function of neutrophils through dihydrorhodamine (DHR) 123 testing, and genotyped 361 genes related to IEI through targeted (panel) sequencing.

Results: The median age of the 53 individuals was four months (IQ 1.5-12), and 52.8% were male. Forty-eight (90.6%) individuals presented only locoregional AE and five (9.4%) presented both locoregional and disseminated AE. Nine (16.9%) patients were diagnosed with an IEI. Four of them presented BCGitis and five presented BCGosis after BCG vaccination. Clinically, four presented chronic granulomatous disease (CGD), three Mendelian susceptibility to mycobacterial disease (MSMD), and two severe combined immunodeficiency (SCID). Patients with IEI had a higher frequency of systemic symptomatology (p = 0.002), history of other infections (p < 0.001), parental consanguinity (p = 0.01), familial history of sick siblings (p < 0.001), or early deaths in the family (p < 0.01).

Conclusion: There is a high frequency of IEI in patients with locoregional and disseminated adverse events to BCG vaccination, revealing the need for the investigation of IEI accompanied by clinical and familial inquiry.

Keywords: Bacille Calmette-Guérin (BCG); Chronic granulomatous disease (CGD); Mendelian susceptibility to mycobacterial disease (MSMD); Primary immunodeficiency; Severe combined immunodeficiency (SCID).

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