Beyerlein Andreas, Strobl Andreas N, Winkler Christiane, Carpus Michaela, Knopff Annette, Donnachie Ewan, Ankerst Donna P, Ziegler Anette-G
Institute of Diabetes Research, Helmholtz Zentrum München, Munich, Germany; Forschergruppe Diabetes der Technischen Universität München, Munich, Germany.
Department of Mathematics of the Technische Universität München, Munich, Germany.
Vaccine. 2017 Mar 27;35(14):1735-1741. doi: 10.1016/j.vaccine.2017.02.049. Epub 2017 Mar 3.
AIMS/HYPOTHESIS: Vaccinations in early childhood potentially stimulate the immune system and may thus be relevant for the pathogenesis of autoimmune diseases such as type 1 diabetes (T1D). We determined the association of vaccination burden with T1D-associated islet autoimmunity in children with high familial risk followed prospectively from birth.
A total of 20,570 certified vaccination records from 1918 children were correlated with time to onset of T1D-associated islet autoimmunity using Cox regression, considering multiple time periods up until age two years and vaccination types, and adjusting for HLA genotype, sex, delivery mode, season of birth, preterm delivery and maternal T1D status. Additionally, prospective claims data of 295,420 subjects were used to validate associations for the tick-borne encephalitis (TBE) vaccination.
Most vaccinations were not associated with a significantly increased hazard ratio (HR) for islet autoimmunity (e.g. HR [95% confidence interval]: 1.08 [0.96-1.21] per additional vaccination against measles, mumps and rubella at age 0-24months). TBE vaccinations within the first two years of life were nominally associated with a significantly increased autoimmunity risk (HR: 1.44 [1.06-1.96] per additional vaccination at age 0-24months), but this could not be confirmed with respect to outcome T1D in the validation cohort (HR: 1.02 [0.90-1.16]).
We found no evidence that early vaccinations increase the risk of T1D-associated islet autoimmunity development. The potential association with early TBE vaccinations could not be confirmed in an independent cohort and appears to be a false positive finding.
目的/假设：幼儿期接种疫苗可能刺激免疫系统，因此可能与1型糖尿病（T1D）等自身免疫性疾病的发病机制相关。我们前瞻性地追踪了出生时具有高家族风险的儿童，确定了疫苗接种负担与T1D相关胰岛自身免疫之间的关联。
使用Cox回归分析，将1918名儿童的20570份经认证的疫苗接种记录与T1D相关胰岛自身免疫的发病时间相关联，考虑到两岁之前的多个时间段和疫苗接种类型，并对HLA基因型、性别、分娩方式、出生季节、早产和母亲T1D状态进行了调整。此外，还使用了295420名受试者的前瞻性索赔数据来验证蜱传脑炎（TBE）疫苗接种的关联。
大多数疫苗接种与胰岛自身免疫的风险比（HR）显著增加无关（例如，0至24个月龄时每额外接种一剂麻疹、腮腺炎和风疹疫苗，HR [95%置信区间]：1.08 [0.96 - 1.21]）。生命最初两年内接种TBE疫苗名义上与自身免疫风险显著增加相关（0至24个月龄时每额外接种一剂，HR：1.44 [1.06 - 1.96]），但在验证队列中关于T1D结局无法得到证实（HR：1.02 [0.90 - 1.16]）。
我们没有发现证据表明早期接种疫苗会增加T1D相关胰岛自身免疫发展的风险。与早期TBE疫苗接种的潜在关联在独立队列中无法得到证实，似乎是一个假阳性结果。
