Predicting anti-RhD titers in donors: Boostering response and decline rates are personal

BackgroundAnti-RhD immunised donors provide anti-RhD immunoglobulins used for the prevention of rhesus disease. These donors are periodically hyper-immunised (boostered) to retain a high titer level of anti-RhD.Study design and methodsWe analysed anti-RhD donor records from 1998 to 2016, consisting of 30,116 anti-RhD titers from 755 donors, encompassing 3,372 booster events. Various models were fit to these data to allow describing the anti-RhD titers over time.ResultsA random effects model with a log-linear anti-RhD titer decline over time and a saturating titer response to boostering is shown to fit the data well. This model contains two general model parameters, relating timing and maximum of the booster effect, as well as two parameters characterizing the individual donor, namely how fast the booster effect saturates with current titer and the anti-RhD decline rate. The average individual log2 decline is 0.55 per year, i.e. a 32% decline in absolute titer, with half of the donors declining between 13% and 41% per year. Their anti-RhD titer peaks around 26 days following a booster event. Boostering response reduces with higher titers at boostering; at median titer (log2 11) the mean increase per booster is log2 0.38, that is from an absolute titer of 2048 to 2665 (+30%), with half of all donors increasing between 16% and 65% in their titer.ConclusionThe model describes anti-RhD titer change per individual with only four parameters, two of which are donor specific. This information can be used to enhance the blood bank’s immunisation programme, by deriving individualized immunization policies in which boostering is adjusted to the anticipated anti-RhD decline, effectiveness of boostering and titer levels required.**背景**：抗RhD免疫供者可提供用于预防Rh溶血病（rhesus disease）的抗RhD免疫球蛋白（anti-RhD immunoglobulins）。此类供者需定期接受强化免疫（boostering），以维持抗RhD的高滴度（titer）水平。**研究设计与方法**：本研究分析了1998年至2016年间的抗RhD免疫供者记录，涵盖755名供者的30116份抗RhD滴度数据，包含3372次加强免疫事件。我们对该数据集拟合了多种模型，以描述抗RhD滴度随时间的变化趋势。**结果**：本研究发现，采用具有对数线性（log-linear）抗RhD滴度随时间衰减特征、且对加强免疫呈现饱和滴度响应的随机效应模型（random effects model），可很好地拟合本数据集。该模型包含2个通用模型参数，分别与加强免疫效应的发生时机及最大效应相关；此外还有2个表征个体供者特征的参数，即加强免疫效应随当前滴度达到饱和的速率，以及抗RhD滴度的衰减速率。供者个体的平均log₂滴度衰减速率为每年0.55，对应绝对滴度下降32%；其中半数供者的年衰减幅度介于13%至41%之间。供者的抗RhD滴度在加强免疫后约26天时达到峰值。加强免疫的响应强度会随加强免疫时的滴度升高而降低：在中位滴度（log₂11）时，单次加强免疫的平均滴度提升为log₂0.38，即绝对滴度从2048升至2665（提升30%），且半数供者的滴度提升幅度介于16%至65%之间。**结论**：该模型仅通过4个参数即可描述每名供者的抗RhD滴度变化，其中2个参数为供者特异性参数。本研究结果可用于优化血站的免疫规划：通过制定个体化免疫策略，根据预期的抗RhD滴度衰减情况、加强免疫的效果及所需滴度水平，对加强免疫方案进行调整。