Background: Population-based screening for celiac disease (CeD) requires sampling methods that can accommodate large testing volumes while ensuring robust sampling handling, high analytical reliability and broad accessibility. Dried blood spot (DBS) cards require only a small blood volume, are easy to use and can be transported efficiently between homes, clinics, and laboratories worldwide. However, DBS are susceptible to haemolysis, which may affect tissue transglutaminase autoantibody (tTGA) measurements and comprise diagnostic accuracy. In this context, plasma separation cards (PSC) may offer advantages by improving sample quality while maintaining the logistical benefits of capillary sampling.
Methods: Autoantibodies associated with CeD, type 1 diabetes (T1D) and autoimmune thyroiditis (AITD) were measured using autoantibody detection by agglutination-PCR (ADAP) in centrifuged plasma, PSC, and DBS. The study included autoantibody-positive individuals (n=77), healthy children served as controls (n=613), as well as children undergoing gastroscopy for suspected CeD (n=37). Agreement between sampling methods was assessed using Cohen's kappa, and the diagnostic performance of tTGA was evaluated by receiver operating characteristic (ROC) curve analysis.
Results: PSC demonstrated high diagnostic accuracy for tTGA compared with plasma (AUC 0.98; sensitivity 92.7% and specificity 95.4%; p=0.34)), whereas DBS showed markedly lower performance (AUC 0.53; sensitivity 19.4%; p<0.001). As comparison, DBS showed substantial to almost perfect agreement with plasma (κ=0.77-0.90) for T1D and AITD associated autoantibodies, but with a directional bias toward lower detected signals.
Conclusion: PSC demonstrated excellent diagnostic accuracy for tTGA and outperformed DBS CeD screening while maintaining comparable performance for T1D and AITD associated autoantibodies. These findings support PSC as a reliable and scalable sampling method for large-scale, population-based screening programmes requiring high-throughput processing of capillary samples.