원문
Shin H, Lee HS, Noh JY, et al. COVID-19 Vaccination Alters NK Cell Dynamics and Transiently Reduces HBsAg Titers Among Patients With Chronic Hepatitis B. Immune Netw. 2023;23(5):e39.
출판사 페이지에서 원문 보기
한 문단 요약흥미로운 발견이에요. COVID-19 백신 접종이 만성 B형간염 환자의 NK 세포 동태를 변화시키고 HBsAg 농도를 일시적으로 줄였습니다. "감염성 자극"이 면역체계를 흔들어 잠복 바이러스 표지자에 영향을 줄 수 있다는 가설을 뒷받침하는 데이터입니다. 향후 면역 매개 functional cure 전략 개발에 단서가 될 수 있어요.
B형간염 functional cure(HBsAg 소실)는 현재 표준 치료로 도달률이 낮은데, 면역체계를 자극하면 도달률을 높일 수 있다는 가설이 있어요. COVID-19 백신은 mRNA 또는 단백 기반의 강력한 면역 자극이라, 우연한 "자연 실험"으로 면역과 HBV(B형간염 바이러스) 표지자의 관계를 볼 기회가 됐습니다.
Figure 1. Median HBsAg differences from baseline in each patient following COVID-19 vaccination in vaccinated patients or after the index date in unvaccinated patients. HBsAg titers were measured and compared to baseline values in each patient. (A) Plot of the differences in HBsAg from baseline and the time interval between the date of the test and the date of the vaccination for each vaccinated patient. The length of the time following vaccination was grouped into 5 periods: days −360 to −181, −180 to −1, +1 to +30, +31 to +90, and +91 to +180. (B) Plot of the differences in HBsAg from baseline and test date from the index date in each unvaccinated patient. Time after index date was grouped into 5 periods: days −360 to −181, −180 to −1, +1 to +30, +31 to +90, and +91 to +180. If time groups included multiple samples from the same patient, the median value was used in the analysis. Dots and error bars represent median and IQR *** p<0.001 according to a Wilcoxon signed-rank test for paired groups and Mann-Whitney U test for unpaired groups.
APPROACH접근 방식
COVID-19 백신 접종 전후로 만성 B형간염 환자의 NK 세포 표현형(CD56·CD16 등) 변화와 HBsAg 정량(quant) 변화를 추적합니다. 일반 인구의 백신 접종 후 면역 변화와 비교해 HBV 환자에서의 특이성을 확인합니다.
Figure 2. Frequency and phenotype of peripheral blood NK cells after COVID-19 vaccination. The frequency and phenotype of NK cells were examined using 166 serial PBMC samples from 25 healthy participants (11 participants vaccinated with BNT162b2 and 14 with AZD1222). Time after vaccination was grouped into 3 periods: days +1 to +7, +8 to +30, and +31 to +72. If time groups included multiple samples from the same participant, the median value was used in the analysis. (A) Changes in the relative frequency of CD56 + CD3 − NK cells, (B) CD56 bright CD16 − NK cells, and (C) CD56 dim CD16 + NK cells among lymphocytes (n=25) compared to baseline. (D) Changes in the relative frequency of NK cells expressing NKG2A, (E) KIRs, (F) TIGIT, (G) NKp30, (H) NKp46, and (I) NKG2C among total NK cells (n=25) compared to baseline. Dots and error bars represent median and IQR ns, not significant. *** p<0.001 according to Wilcoxon signed-rank test for paired groups and Mann-Whitney U test for unpaired groups.
KEY POINT임상 함의
HBsAg 감소가 일시적이지만 면역 매개로 일어났다는 점이 의미 있어요. 면역조절제(TLR 작용제, 면역체크포인트 억제 등)가 HBV functional cure 임상시험에서 활발히 연구 중인 배경과 연결됩니다. 다만 임상에서 "COVID 백신으로 B형간염을 치료한다"는 결론은 아니에요 — 표지자 변화의 일시성과 임상 중요성은 별개입니다.
Figure 3. Frequency of NKG2A + cells in CD56 dim CD16 + and CD56 bright CD16 − NK cells after COVID-19 vaccination. Time after vaccination was grouped into 3 periods: days +1 to +7, +8 to +30, and +31 to +72. If time groups included multiple samples from the same participant, the median value was used in the analysis. (A) Changes in the relative frequency of NKG2A + cells among CD56 dim CD16 + NK cells and (B) CD56 bright CD16 − NK cells (n=25) compared to baseline. (C) Changes in the relative frequency of NKG2A + cells in CD56 dim CD16 + NK cells among subgroups of BNT162b2 (n=11) and (D) AZD1222 (n=14) compared to baseline. Dots and error bars represent median and IQR ns, not significant. * p<0.05, *** p<0.001, **** p<0.0001 according to Wilcoxon signed-rank test for paired groups and Mann-Whitney U test for unpaired groups.
References
Shin H, Lee HS, Noh JY, et al. COVID-19 Vaccination Alters NK Cell Dynamics and Transiently Reduces HBsAg Titers Among Patients With Chronic Hepatitis B. Immune Netw. 2023;23(5):e39. DOI · PMID 37970236
