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Interferon-gamma-dependent Immunity in Bacillus Calmette-Guérin Vaccine Osteitis Survivors.
Pediatr Infect Dis J. 2016 06;35(6):690-4
Authors: Pöyhönen L, Kröger L, Huhtala H, Mäkinen J, Mertsola J, Martinez-Barricarte R, Casanova JL, Bustamante J, He Q, Korppi M
Abstract
BACKGROUND: Inborn errors of interferon-gamma (IFN-γ)-mediated immunity underlie disseminated disease caused by Mycobacterium bovis Bacillus Calmette-Guérin (BCG) live vaccines. We hypothesized that some patients with osteitis after BCG vaccination may have an impaired IFN-γ immunity. Our aim was to investigate interleukin (IL)-12 and IFN-γ ex vivo production stimulated with BCG and BCG + IFN-γ or BCG + IL-12, respectively, in BCG osteitis survivors.
METHODS: Fresh blood samples were collected from 132 former BCG osteitis Finnish patients now aged 21-49 years, and IL-12 and IFN-γ were measured in cell cultures with and without stimulation with BCG and with BCG + IFN-γ or BCG + IL-12, respectively. As a pilot study, known disease-causing genes controlling IFN-γ immunity (IFNGR1, IFNGR2, STAT1, IL12B, IL12RB1, ISG15, IRF8, NEMO and CYBB) were investigated in 20 selected patients by whole exome sequencing.
RESULTS: By the limit of <5th percentile, ex vivo IL-12 concentration and increase in concentration was low in 5 and ex vivo IFN-γ concentration and increase in concentration was low in 6 patients (including 2 samples with both IL-12 and IFN-γ findings). By the limit of <10th percentile, an additional 6 and 4 patients were, respectively, detected (including 2 samples with both findings). With 2 exceptions, low concentrations and low increases in concentrations picked-up the same cases. Mutations in known disease-causing IFN-γ-related genes were not found in any of these patients.
CONCLUSION: These findings call for searching of mutations in new genes governing IFN-γ-dependent immunity to live BCG vaccine.
PMID: 26954602 [PubMed - indexed for MEDLINE]
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