From the Division of Immunology and Rheumatology, Department of Medicine, Stanford University, Stanford, California (M.C.B. and S.T.), the Department of Clinical Epidemiology, Aarhus University Hospital and Department of Clinical Medicine, Aarhus University, Aarhus, Denmark (E.V., E.H.P., and H.T.S.), and the Clinical Excellence Science Center, Stanford University, Stanford, California (H.T.S.), United States of America.
From the Division of Immunology and Rheumatology, Department of Medicine, Stanford University, Stanford, California (M.C.B. and S.T.), the Department of Clinical Epidemiology, Aarhus University Hospital and Department of Clinical Medicine, Aarhus University, Aarhus, Denmark (E.V., E.H.P., and H.T.S.), and the Clinical Excellence Science Center, Stanford University, Stanford, California (H.T.S.), United States of America.
Semin Arthritis Rheum. 2023 Jun;60:152205. doi: 10.1016/j.semarthrit.2023.152205. Epub 2023 Apr 6.
Sarcoidosis may have an infectious trigger, including Mycobacterium spp. The Bacille Calmette-Guérin (BCG) vaccine provides partial protection against tuberculosis and induces trained immunity. We examined the incidence rate (IR) of sarcoidosis in Danish individuals born during high BCG vaccine uptake (born before 1976) compared with individuals born during low BCG vaccine uptake (born in or after 1976).
We performed a quasi-randomized registry-based incidence study using data from the Danish Civil Registration System and the Danish National Patient Registry between 1995 and 2016. We included individuals aged 25-35 years old and born between 1970 and 1981. Using Poisson regression models, we calculated the incidence rate ratio (IRR) of sarcoidosis in individuals born during low BCG vaccine uptake versus high BCG vaccine uptake, adjusting for age and calendar year (separately for men and women).
The IR of sarcoidosis was increased for individuals born during low BCG vaccine uptake compared with individuals born during high BCG vaccine uptake, which was largely attributed to men. The IRR of sarcoidosis for men born during low BCG vaccine uptake versus high BCG vaccine uptake was 1.22 (95% confidence interval [CI] 1.02-1.45). In women, the IRR was 1.08 (95% CI 0.88-1.31).
In this quasi-experimental study that minimizes confounding, the time period with high BCG vaccine uptake was associated with a lower incidence rate of sarcoidosis in men, with a similar effect seen in women that did not reach significance. Our findings support a potential protective effect of BCG vaccination against the development of sarcoidosis. Future interventional studies for high-risk individuals could be considered.
结节病可能存在包括分枝杆菌属在内的感染诱因。卡介苗（BCG）疫苗可提供针对结核病的部分保护，并诱导获得性免疫。我们检测了丹麦在高卡介苗疫苗接种（1976 年前出生）时期出生与低卡介苗疫苗接种（1976 年后出生）时期出生的个体中结节病的发病率（IR）。
我们使用丹麦民事登记系统和丹麦国家患者登记处的数据进行了一项基于登记的准随机发病率研究，时间范围为 1995 年至 2016 年。我们纳入了年龄在 25-35 岁之间，1970 年至 1981 年出生的个体。使用泊松回归模型，我们计算了低卡介苗疫苗接种时期出生与高卡介苗疫苗接种时期出生的个体中结节病的发病率比值（IRR），同时调整了年龄和日历年份（分别针对男性和女性）。
与高卡介苗疫苗接种时期出生的个体相比，低卡介苗疫苗接种时期出生的个体的结节病发病率增加，这主要归因于男性。低卡介苗疫苗接种时期出生的男性与高卡介苗疫苗接种时期出生的男性相比，结节病的发病率比值（IRR）为 1.22（95%置信区间 [CI] 1.02-1.45）。在女性中，IRR 为 1.08（95% CI 0.88-1.31）。
在这项最大限度减少混杂的准实验研究中，高卡介苗疫苗接种时期与男性结节病发病率降低相关，而在女性中也观察到了相似但未达到统计学意义的效果。我们的研究结果支持卡介苗接种对结节病发生具有潜在的保护作用。对于高危个体，未来可能需要开展干预性研究。
