Primary Immunodeficiency Diseases with BCG-Induced Diseases: A 15-Year Longitudinal Cohort Study.

Abstract

BACKGROUNDS: Children with primary immunodeficiency (PID) may develop severe infections after BCG vaccination. There is limited information on the long-term prognosis and management of these BCG-induced diseases. METHODS: Data were gathered from a cohort study on BCG-induced diseases at the Shanghai Public Health Clinical Center, spanning from January 2007 to August 2022. The study enrolled patients with confirmed PIDs, and information was obtained via personal interviews with patients or their guardians, as well as from their medical records. This allowed us to gather clinical and genetic details, treatment history, and the outcomes of their PIDs. We evaluated antimycobacterial outcomes and analyzed the impact of HSCT and IFN-γ therapy on the risk of death. RESULTS: Out of 422 patients with BCG-induced diseases, 109 patients with confirmed PID were included in the analysis. Of these, 88.1% had developed distant or disseminated BCG infection, and the median duration of illness documented in the study was 57 months (IQR 31–79). The three most common PIDs in this cohort were MSMD (47/109, 43.1%), CGD (28/109, 25.7%), and CID (19/109 or 17.4%). The estimated five-year and ten-year survival rates were 80.3% (95%CI, 72.1%-88.5%) and 69.3% (95%CI, 56.8%-81.8%). Patients who received hematopoietic stem cell transplantation therapy (HSCT) had a significantly higher success rate with antimycobacterial treatment (75.8% vs. 0%). The survival benefit of HSCT varies across immunodeficiency types but is clearly beneficial for CID (p < 0.001). IFN-γ therapy presented no significant effect on the survival of CGD and MSMD. The initial STRONGkids nutritional score (HR = 2.27 per point, 95%CI 1.65–3.13) and gender (HR for male = 4.89, CI 1.36–17.57) are significant predictors of survival. Mutations in 6 genes (IL12RB1, CYBB, IFNGR1, IL2RG, STAT1, and RAG1) account for 66% of BCG-associated immunodeficiency mutations. CONCLUSIONS: PID complicated by BCG infection may cause persistent and severe conditions. Patients with severe nutritional risk in the early stages of infection have a higher risk of death and should prioritize HSCT.