Effect of neonatal BCG vaccination on the evolution of Hashimoto’s Thyroiditis

ABSTRACT Background Hashimoto’s thyroiditis (HT) involves the autoimmune destruction of thyrocytes with the presence of anti-thyroid peroxidase (TPO) and/or anti-thyroglobulin (TG) antibodies. In autoimmune diseases, an immunomodulatory role of Bacillus Calmette-Guerin (BCG) vaccination has been reported with decreased autoantibody production and induction of regulatory T cells. We hypothesize that a decline in the efficacy of BCG might be associated with the appearance of HT during adulthood. Methods Adult subjects with subclinical HT (HT-SCH) (n=39) and non-autoimmune subclinical hypothyroidism (NA-SCH) (n=25) were enrolled along with euthyroid healthy controls (HC) (n=20). The BCG-specific immune responses were determined by the Mantoux test and BCG-induced in-vitro proliferation of peripheral blood mononuclear cells (PBMC). Anti-thyroid cellular immune responses were assessed in subjects with human leukocyte antigen (HLA)-A*02 and HLA-A*24 alleles by determining the frequency of CD8+ T cells recognizing major histocompatibility complex (MHC) dextramers (DMR) carrying TPO-derived peptides, by flow cytometry. Results The HT-SCH group had a lower rate of Mantoux test reactivity (38.5%) as compared to NA-SCH (64%) and HC subjects (65%) (p=0.047). However, the BCG-induced in-vitro proliferation of PBMC was similar in HT-SCH, NA-SCH, and HC groups. Further, the BCG-vaccinated SCH subjects had lower levels of thyroid stimulating hormone (TSH) (p=0.026). Next, the SCH subjects had higher frequencies of peripheral DMR+ CD8+ T cells as compared to HC subjects (p=0.001). Interestingly, the frequency of peripheral DMR+ CD8+ T cells was significantly higher in HT-SCH than HC subjects (p=0.045). Finally, we observed a positive correlation between the frequency of DMR+CD8+ T cells and TSH levels (r = +0.620, p=0.006). Conclusions Collectively, our results highlight a complex relationship of neonatal BCG vaccination with the genesis of HT, via modulation of autoimmune responses directed towards thyroid autoantigens.